Candida albicans

J Cardiovasc Surg (Torino), 1986 May-Jun, 27(3), 341 - 3
Surgical therapy of pulmonary thrombosis due to candidiasis in a premature infant; Gorlach G et al.; We report a case of surgical removal of a pulmonary thrombosis in a premature infant with candidemia . The pulmonary thrombotic material contained candida albicans . Following surgical therapy the child recovered soon and candidemia did not recur . We conclude that surgical treatment of pulmonary thrombosis can be successfully done even in premature infants.

J Invest Dermatol, 1986 May, 86(5), 556 - 9
Effect of hair growth cycles on experimental cutaneous candidiasis in mice; Sohnle PG et al.; Experimental cutaneous Candida albicans infections were produced in mice by inoculating the organisms onto areas of shaved flank skin where the hair follicles were in either the anagen (growing) or telogen (resting) phase of the growth cycle . Infection with Candida occurred in a majority of animals inoculated on either anagen or telogen skin, and the rate of clearance of the organisms was equivalent for infections on the 2 types of skin . Some of the animals inoculated on anagen skin developed foci of Candida infection in the well-developed hair follicles, below the skin surface . Deep foci of infection were not found after inoculation of the telogen areas . The infections resulted in increases in epidermal thickness and sensitization of the animals to Candida antigens, but these responses were not different between animals inoculated on the 2 types of skin . The results of these experiments indicate that although Candida albicans can infect skin containing either active or resting hair follicles, foci of infection below the skin surface occur only when well-developed hair follicles are present . These findings may have relevance to the consequences of human cutaneous candidiasis.

J Nutr, 1986 May, 116(5), 816 - 22
The response of selenium-deficient mice to Candida albicans infection; Boyne R et al.; The effects of selenium deficiency on the responses to Candida albicans infection were examined in mice . When selenium-deficient and selenium-supplemented mice were given i.v . injections of 0.1 ml suspensions of 1 X 10(5) or 5 X 10(4) C . albicans in 0.9% sterile saline, deaths in the selenium-deficient animals started after 2.5-3.5 d compared with 7-8.5 d in the selenium-supplemented animals . Further studies demonstrated that 3 d after an i.v . injection of 1 X 10(5) C . albicans, significantly more of the microorganisms were found in the kidneys (P less than 0.001), livers (P less than 0.025) and spleens (P less than 0.01) of the selenium-deficient mice compared with the same organs of selenium-supplemented animals . Selenium deficiency was also demonstrated to impair the ability of mouse neutrophils to kill C . albicans in in vitro tests . The possible relationships of this defect in function to decreased resistance to C . albicans infection is discussed.

Antimicrob Agents Chemother, 1986 May, 29(5), 858 - 60
Ergosterol biosynthesis inhibition by the thiocarbamate antifungal agents tolnaftate and tolciclate; Ryder NS et al.; The thiocarbamate antimycotics tolnaftate and tolciclate blocked sterol biosynthesis in fungal cells and cell extracts, with accumulation of squalene . This point of action was confirmed by the direct inhibition of microsomal squalene epoxidase from Candida albicans . There was no inhibition of other steps in ergosterol biosynthesis . In whole Candida cells, ergosterol biosynthesis inhibition was not complete at drug concentrations up to 100 mg/liter, whereas full inhibition occurred in a cell-free test system . Rat liver cell-free cholesterol biosynthesis was much less sensitive to the drugs . The biochemical action of tolnaftate and tolciclate is thus similar to that of the allylamine antimycotics naftifine and terbinafine.

Antimicrob Agents Chemother, 1986 May, 29(5), 726 - 9
Complementation analysis of resistance to 5-fluorocytosine in Candida albicans; Whelan WL et al.; A complementation test was devised to study allelism among the genetic determinants of resistance to 5-fluorocytosine in Candida albicans . Complementation was demonstrated in control hybrids produced by crossing a resistant strain that was deficient in cytosine deaminase activity with four other resistant strains deficient in UMP pyrophosphorylase activity . This complementation test was used to test allelism of the resistance determinants present in five clinical isolates . All were found to bear recessive alleles of the locus (FCY1) that determined 5-fluorocytosine resistance associated with low levels of UMP pyrophosphorylase activity.

Mycopathologia, 1986 May, 94(2), 85 - 9
In vitro modification of Candida albicans invasiveness; Fontenla de Petrino SE et al.; Candida albicans produces germ-tubes (GT) when it is incubated in animal or human serum . This dimorphism is responsible for its invasive ability . The purpose of the present paper is (1) to evaluate the ability of rat peritoneal macrophages to inhibit GT production of ingested Candida albicans, obtained from immunized rats and then activated in vitro with Candida-induced lymphokines; (2) to determinate any possible alteration of phagocytic and candidacidal activities . The phagocytes were obtained from rats immunized with viable C . albicans . Some of them were exposed to Candida-induced lymphokines in order to activate the macrophages in vitro . The monolayers of activated, immune and normal macrophages were infected with a C . albicans suspension during 4 hr . Activated macrophages presented not only the highest phagocytic and candidacidal activities but a noticeable inhibition of GT formation and incremented candidacidal activity.

J Clin Microbiol, 1986 May, 23(5), 881 - 6
Production and characterization of agglutinating monoclonal antibodies against predominant antigenic factors for Candida albicans; Miyakawa Y et al.; Two clones, CA4-2 and CA5-4, which produced agglutinating monoclonal immunoglobulin M (IgM) antibodies (MAbs) against mannan antigens of Candida albicans serotype A, were established . The specificity of each MAb was determined by slide agglutination tests for cross-reactivity patterns against the homologous and six other strains of Candida and a strain of Torulopsis: C . albicans serotype B, C . tropicalis, C . guilliermondii, C . krusei, C . parapsilosis, C . pseudotropicalis, and Torulopsis glabrata . The MAb produced by CA4-2 reacted with the homologous, C . tropicalis, and T . glabrata strains, whereas the MAb produced by CA5-4 reacted with the homologous, C . albicans serotype B, and C . tropicalis strains . These results are consistent with results obtained by comparative experiments with several strains of each serotype or species . Specificity of these two MAbs by agglutination was also consistent with the cross-reactivity patterns demonstrated by indirect immunofluorescence staining . The competitive binding experiments by immunofluorescence staining with two MAbs and polyclonal factor sera (PAb factors) 5 and 6 suggested that the MAb from clone CA4-2 did not completely correspond to PAb factor 6 and that the MAb from CA5-4 was distinct from PAb factor 5 in its manner of binding to determinants (the latter was designated 5b), Cross-reactivity patterns, however, furnished evidence that these two MAbs could replace the known PAb factors 6 and 5, respectively, as reagents for aid in the identification of the strains of C . albicans and their serotypes.

Am J Pathol, 1986 May, 123(2), 241 - 9
Participation of neutrophils and delayed hypersensitivity in the clearance of experimental cutaneous candidiasis in mice; Wilson BD et al.; Involvement of neutrophils and delayed hypersensitivity in the clearance of Candida albicans infections was investigated with the use of a model of the disease in inbred mice . Experimental infections were produced by rubbing C albicans onto the shaved skin of the flank without the use of occlusive dressings . After a single infection, delayed hypersensitivity to Candida developed in C57BL/6 mice, and the infection cleared more rapidly than in C3H/He mice, in which delayed hypersensitivity did not develop . In both strains, the organisms were associated with neutrophilic microabscesses in the upper epidermis within 1 day of inoculation; by 3 days, the organisms and microabscesses had become relocated to a site just above the skin surface . At this time, the epidermis was intact under the microabscesses and significantly thickened, which indicated that epidermal proliferation had occurred . Delayed hypersensitivity reactions accelerated clearance of the infection, apparently by increasing the rate of removal of the microabscesses and associated organisms from the skin surface . However, delayed hypersensitivity was not an absolute requirement for clearance, because in animals of the C3H/He strain, in which delayed hypersensitivity did not develop during the first infection, the infection was eventually cleared . It is postulated that in these infections an important defense mechanism may be the enhancement, perhaps by the neutrophilic infiltrate, of epidermal proliferation early in the infection such that the infecting organisms are moved to a location above the skin surface from which they can be more easily removed by other processes, including delayed hypersensitivity reactions.

J Med Microbiol, 1986 May, 21(3), 209 - 13
Effect of saliva and serum on the adherence of Candida species to chlorhexidine-treated denture acrylic; McCourtie J et al.; The effect of saliva and serum on the adherence of five strains of Candida albicans and one each of C . tropicalis and C . glabrata to chlorhexidine-pretreated acrylic was measured in vitro . A four-fold dilution of saliva or serum significantly inactivated the fungicidal effect of chlorhexidine gluconate . Pretreatment of the acrylic with unstimulated mixed saliva for 30 min led to a reduced adherence for all the Candida strains tested, whilst a similar pretreatment with serum slightly increased adhesion . Moreover treatment of saliva- or serum-coated acrylic with chlorhexidine gluconate 2% reduced adherence by between 19% and 86% . The inhibition of yeast adherence by chlorhexidine persisted for up to 19 days after the exposure of the acrylic strips to the disinfectant.

J Immunol, 1986 May 1, 136(9), 3198 - 203
Role of the LFA-1 molecule in cellular interactions required for antibody production in humans; Fischer A et al.; The lymphocyte function-associated antigen 1 (LFA-1) has been shown to play a role in various T cell functions in mice and humans including cytotoxicity, and proliferation to allogeneic cells and foreign antigens . These functions have been defined with specific monoclonal antibodies and were additionally confirmed by the investigation of patients with inherited deficiency in membrane LFA-1 expression . In this paper, we report our studies on the potential role of the LFA-1 molecule in T lymphocyte-dependent antibody responses . In a patient with a complete lack of membrane expression of LFA-1, there was no in vivo antibody response to vaccinal antigens such as tetanus, diphtheria toxoids, and polio virus, and no in vivo or in vitro antibody production to influenza virus, whereas serum immunoglobulin levels and antibodies to polysaccharides (isohemagglutinins, antibody to mannan, and a polysaccharide from Candida albicans) were detected in correlation with in vitro production of anti-mannan antibody . The defective antibody response to polypeptides was not secondary to poor antigen-specific T proliferation, because the latter was found to be present . Similarly, in vitro antibody production to influenza virus of normal cells was blocked by several anti LFA-1 monoclonal antibodies specific for the alpha subunit of the molecule, if they were added from the beginning of the culture . The antibody production blockade could be achieved with monoclonal antibody concentrations that partially preserved T cell proliferation . The helper effect of an influenza virus-specific helper T cell clone was also blocked . The targets of the blockade were shown by incubation experiments to be T cells and monocytes . In contrast, anti-LFA-1 monoclonal antibodies had no effect on pokeweed mitogen-induced B cell maturation into immunoglobulin-containing cells and on the anti-mannan antibody production . These combined data demonstrate that the LFA-1 molecule plays a role in T cell dependent antibody production to polypeptidic antigens but not in the antibody response to polysaccharides, although the antibody response to mannan is T cell dependent . It is proposed that the LFA-1 molecule is required to some extent for a antigen-presenting cells-T lymphocyte interaction and for the maintenance of a close association between antigen-specific helper T cells and small resting B lymphocytes . Polysaccharidic antigens that exhibit repetitive antigenic determinants might cross-link membrane immunoglobulins on B lymphocytes, thus allowing B cells to pass through a first step of activation requiring cognate T-B cell interaction.

Hum Immunol, 1986 May, 16(1), 114 - 25
Restriction of the in vitro anti-mannan antibody response by HLA-DQ molecules; Durandy A et al.; In humans, the in vitro antibody response directed towards mannan, a polysaccharide extracted from the cell wall of Candida albicans, has been previously shown to be dependent on the presence of T lymphocytes and monocytes . Evidence is now given for the existence of a genetic restriction governing this response since antibody production is achieved provided that monocytes and T lymphocytes on one side and monocytes and B lymphocytes on the other side are of the same origin . In order to delineate the restriction element governing these interactions, blocking experiments have been designed using well-defined monoclonal antibody, anti-HLA class II molecules . The results clearly indicate that the restriction element belongs to the HLA-DQ molecular series, as shown in T-cell proliferation and antibody production assays in the presence of either T cells or T-cell supernatants . Incubation of isolated cell populations (T, B lymphocytes and monocytes) with the monoclonal antibody have indicated that DQ determinants are involved in the mannan presentation by monocytes to T and B cells . The HLA-DQ mediated restriction of the in vitro immune response to mannan has been observed in all the subjects tested, suggesting that mannan epitopes are preferentially, or even only, recognized in association with an unique group of HLA-class II molecules, namely HLA-DQ.

J Oral Pathol, 1986 May, 15(5), 251 - 4
Growth and acid production of Candida species in human saliva supplemented with glucose; Samaranayake LP et al.; Growth characteristic and acid production of oral isolates of Candida albicans and Candida glabrata in glucose supplemented and glucose-free, pooled, human whole saliva were examined . Both Candida species exhibited sigmoidal growth curves in batch cultures of mixed saliva, supplemented with glucose . The growth of Candida in saliva was accompanied by a rapid decline in pH from 7.5 to 3.2 over 48 h and the major acidic components initiating and sustaining this pH drop were pyruvates and acetates . These acidic metabolites may play an important role in the pathogenesis of oral Candida infections.

J Clin Invest, 1986 May, 77(5), 1557 - 64
Specific binding of antigen onto human T lymphocytes; Durandy A et al.; Human T lymphocytes sensitized to Candida albicans (CA) were shown to proliferate in cultures induced with mannan, a ramified polysaccharide extracted from the cell well of CA . We presently describe that, when we used strongly labeled {3H}mannan, antigen-specific T blast cells were able to bind the labeled mannan on their membrane . The observations that irrelevant blast cells did not bind {3H}mannan, and that mannan-specific blast cells did not bind tritiated pneumococcal polysaccharide SIII, indicate the specificity of mannan binding . Mannan binding was reversible and saturable . Mannan binding on T blast cells was inhibited by preincubation with monoclonal antibodies to T3 but not to other T cell-related molecules . The characteristics of this receptor suggest its identity with the T cell receptor for antigen . The direct binding of mannan could be either due to a cross-linking of the receptor by multivalent mannan or to a recognition of mannan in association with HLA-DQ molecules, as suggested by partial blocking of mannan binding using anti-HLA-DQ monoclonal antibodies.

J Med Chem, 1986 May, 29(5), 802 - 9
Synthesis and biological properties of chitin synthetase inhibitors resistant to cellular peptidases; Shenbagamurthi P et al.; The synthesis and biological properties of seven polyoxins (4-10) designed to avoid peptidase hydrolysis in Candida albicans are presented . Five dipeptidyl and two tripeptidyl polyoxin analogues were synthesized by coupling an amino acid active ester or azlactone to uracil polyoxin C (2) or polyoxin D (1), subsequent removal of the protecting group, and purification by preparative HPLC . A new and novel route for introducing an n-propyl group onto the alpha-amino group of peptides is reported . With the exception of a carboxamide derivative, 8, all analogues were resistant to hydrolysis by a cell extract or permeabilized cells of Candida . Chitin synthetase inhibition constants were determined for 4-10 and the KI values ranged from 7.15 X 10(-6) M for octanoyl-phenylalanyl-polyoxin D (10) to 1.06 X 10(-3) M for D-tryptophanyl-uracil polyoxin C (6) . These novel polyoxins do not compete with the transport of either peptides or uridine into the cell . Millimolar concentrations of compounds 4-10 are required to inhibit growth, cause morphological alterations, or reduce the viability of C . albicans.

Z Gesamte Inn Med, 1986 Apr 15, 41(8), 242 - 4
{Effect of immunoreactivity to candidin on phagocytic performance and intracellular killing of live fungi by polymorphonuclear granulocytes}; Walther T et al.; Positive results of the intracutaneous test with Candida were associated with an increased phagocytosis (p-trend) and an increase of the intracellular killing (p less than or equal to 0.01) of Candida albicans by polymorphonuclear granulocytes.

Cell Immunol, 1986 Apr 15, 99(1), 196 - 208
Presentation of Candida albicans and purified protein derivative soluble antigens by Epstein-Barr virus-transformed human lymphoblastoid B-cell lines; Reitnauer PJ et al.; Cells other than the macrophage can function as antigen-presenting cells (APCs) . These class II-bearing accessory cells include dendritic cells, epidermal Langerhans cells, B cells, murine B-cell tumors, and human Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCL) . We investigated the ability of EBV-LCL to present two soluble antigens, Candida albicans and purified protein derivative of tuberculin (PPD) . The EBV-LCL derived from B cells of two different individuals can present both antigens to bulk cultures of autologous antigen-primed peripheral blood lymphocytes . The responses of PPD-reactive T-cell clones were weaker to PPD when presented by EBV-LCL than by PBL-APCs, with some clones responding only to PPD presented by PBL-APCs . This suggests that EBV-LCL are not equivalent to PBL monocytes in APC function, and that expression of class II major histocompatibility complex antigen is not sufficient in enabling antigen-presenting capability.

Biochim Biophys Acta, 1986 Apr 14, 856(2), 237 - 43
Transport of basic amino acids in Candida albicans; Rao LR et al.; In Candida albicans, ATCC 46977, transport of basic amino acids is mediated by two systems (S1 and S2) . Kinetic data and competitive inhibition studies of the different systems showed that transport of L-lysine, L-arginine and L-histidine have distinct specificities . System S1 of L-lysine and L-arginine was highly specific for the respective single basic amino acid . However, S2 of L-lysine and S1 of L-histidine were shown to be specific systems for most of basic amino acids . S2 of L-arginine was different from S2 of L-lysine and S1 of L-histidine . The effect of a thiol reagent, N-ethylmalemide, revealed that S2 of L-lysine and S1 of L-histidine were sensitive to this reagent, while all other systems were insensitive . The transport activity of different systems of L-lysine, L-arginine and L-histidine was followed during the growth of C . albicans . It was observed that different basic amino-acid systems have maximum activity during different stages of C . albicans growth.

Biochim Biophys Acta, 1986 Apr 11, 881(2), 229 - 35
Purification and properties of three intracellular proteinases from Candida albicans; Portillo F et al.; Three intracellular proteinases termed A, B and C were purified to homogeneity from the unicellular form of the yeast Candida albicans . Enzyme A is an aspartic proteinase that acts on a variety of proteins . Its optimal pH is around 5 and it is displaced to 6.5 by KSCN . It is not significantly inhibited by PMSF, TLCK (Tos-Lys-CHCl2) or soybean trypsin inhibitor but it is inhibited by pepstatin . Its molecular weight is 60 000 . Enzyme B is a dipeptidase that acts on esters or on dipeptides without blocks in either the carboxyl or amino ends . Its pH optimum is around 7.5 and the molecular weight is 57 000 . It is inhibited by PMSF, TLCK and DANME (N2Ac-Nle-OMe) . Proteinase C is an aminopeptidase with an optimum pH around 8 . Its molecular weight was 67 000 when determined by SDS gel electrophoresis and 243 000 when determined by gel weight was 67 000 when determined by SDS gel electrophoresis and 243 000 when determined by gel filtration . It is active towards dipeptides in which at least one amino acid is apolar and is not active when the N-terminal amino acid is blocked . It is inhibited by EDTA or o-phenanthroline and activated by several divalent cations.

Mycopathologia, 1986 Apr, 94(1), 45 - 51
Effect of elevated temperatures and low levels of trace metals on the growth and phenotypic development of Candida albicans; Ismail A et al.; A combination of elevated temperatures (within the human febrile range) and trace metal chelation were investigated for their effects on the inhibition of growth and phenotypic development of the dimorphic yeast Candida albicans (strain 3153A) . The ability of specific cations to relieve the phenotypic inhibition that occurred also was tested . Elevated temperatures alone (to 41 degrees C) only delayed the timing of the phenotypic development . When compared to the results obtained at 37 degrees C, the recombination of elevated temperature and addition of the trace metal chelator, 1,10-phenanthroline, did not further suppress phenotypic development, but the combination did decrease the viability of C . albicans . When 24 to 48 h stationary phase singlet cells were released into a medium containing 100 microM 1,10-phenanthroline (pH 6.5), supplemental iron (200 microM) alleviated the suppression of mycelium formation at 41 degrees C, whereas under conditions favoring bud formation (pH 4.5), both iron and zinc circumvented suppression and promoted budding . Through studies on the interaction of temperature stress and trace metal availability our data revealed the requirement for iron mycelium formation whereas both iron and zinc may be needed for bud formation.

Mycopathologia, 1986 Apr, 94(1), 11 - 7
Immune responses to yeast and mycelial forms of Candida albicans in intraperitoneally infected mice; Ponton J et al.; Candida albicans E-139 produced pure mycelial and yeast cultures in a low sulphate medium at different temperatures . The influence of the morphological phase, dose and viability of the fungi on the kinetic of delayed-type hypersensitivity (DTH) and anti-mycelial and anti-yeast antibodies have been studied in mice injected intraperitoneally . The mycelial form elicited higher DTH levels than the yeast phase . This effect seems to be related to its antigenic properties . The effect of dose on the immune response depends on the viability of the fungus . The mycelial cytoplasmic antigens were more effective than the yeast ones in detecting antibodies induced during the experiments, particularly during the later stages of the observation periods, suggesting that such antigens may be useful in the serodiagnosis of Candida infections.

J Med Vet Mycol, 1986 Apr, 24(2), 165 - 8
A Candida albicans rough-type mutant with increased cell surface hydrophobicity and a structural defect in the cell wall mannan; Shimokawa O et al.; A Candida albicans rough-type mutant showing increased hydrophobicity of the cell surface was isolated . The mutant cells contained about one-quarter as much mannan as the wild type, and were defective in antigenic factors 1, 4, 5, and 6 . Acetolysis fingerprinting demonstrated that the mutant mannan had a structural defect in its carbohydrate skeleton.

J Med Vet Mycol, 1986 Apr, 24(2), 127 - 31
Pathogenesis of vaginal candidiasis: studies with a mutant which has reduced ability to adhere in vitro; Lehrer N et al.; A spontaneous, cerulenin-resistant mutant of Candida albicans (strain 4918-10) was found to adhere less readily to human vaginal mucosal cells in vitro than a wild type C . albicans (strain 4918) . In a murine model of vaginal infection, strain 4918-10 was found to be less virulent than wild type C . albicans, i.e., the infection rate caused by 4918-10 was only 31% of that observed with wild type, 4918 . A chitin-soluble extract (CSE) prepared from 4918 blocked attachment of yeast cells to human vaginal epithelial cells, while CSE from 4918-10 did not significantly reduce the attachment of yeasts to vaginal cells . Both 4918 and 4918-10 produced hyphae in vitro and in vivo, were negative for proteinase production and grew equally well at 28 degrees C and 37 degrees C . The data suggest that adherence to vaginal mucosa may be an important determinant in the pathogenesis of vaginal infection caused by C . albicans.

J Med Vet Mycol, 1986 Apr, 24(2), 121 - 5
Candida albicans adherence in newborn infants; Cox F; Adherence of Candida albicans to buccal epithelial cells from full-term infants was significantly lower than adherence to epithelial cells from premature infants and healthy school-age children, until the full-term infants reached 5 days of age . Adherence in premature infants (gestational age 28-39 weeks) at birth was more than twice that of term infants and remained unchanged during the first week of life . Differences in Candida adherence in premature and term newborns may be due to developmental, salivary, receptor site or other unknown factors.

Microbiologica, 1986 Apr, 9(2), 173 - 8
Phagocytosis of Leishmania infantum promastigotes by monocytes isolated from Leishmania-infected dogs; Brandonisio O et al.; Fifteen dogs with generalised leishmaniasis have been evaluated for their monocyte capacity to ingest Leishmania promastigotes . These cells displayed a lower phagocytic ability when compared to monocytes recovered from normal dogs . Moreover, sera from Leishmania-infected dogs caused a remarkable decrease of monocyte phagocytic ability in healthy dogs, whereas sera from healthy dogs could restore monocyte phagocytosis in sick animals . Similar results were seen when Candida albicans was used as stimulant . Interestingly, supernatants from polyethylenglycole (PEG) treated sera from Leishmania-infected dogs did not inhibit monocyte phagocytosis either in the autologous or in the homologous (healthy dogs) system . This suggests a possible role for serum factor(s) in the impairment of phagocytosis in Leishmania infection.

Antimicrob Agents Chemother, 1986 Apr, 29(4), 701 - 2
Sensitivity of Candida albicans to amphotericin B administered as single or fractionated doses; Sokol-Anderson ML et al.; Candida albicans cells were exposed to equal concentrations of amphotericin B (AmB) administered either as a single large dose or as repeated small doses . Toxicity to C . albicans cells was less pronounced when AmB was administered in fractionated doses . Increased catalase activity in C . albicans cells was induced after exposure to fractionated doses of AmB; this increase may have contributed to the greater resistance of cells to AmB used according to this schedule.

Invest Ophthalmol Vis Sci, 1986 Apr, 27(4), 500 - 6
Rapid visualization of three common fungi using fluorescein-conjugated lectins; Robin JB et al.; The feasibility of using fluorescein-conjugated lectins to visualize and differentiate three fungi commonly involved in ophthalmic mycoses was evaluated . Using a panel of fluorescein-conjugated lectins, Candida albicans, Aspergillus fumigatus, and Fusarium solani were rapidly and reproducibly visualized in in vitro culture isolates, as well as in tissue samples and fixed histopathologic specimens taken from experimental mycoses . Additionally, Aspergillus and Fusarium were consistently differentiated from Candida . The binding affinities of the different lectins corresponded well with the individual sugar composition of the fungal cell walls.

J Oral Pathol, 1986 Apr, 15(4), 213 - 7
Angular cheilitis: a clinical and microbial study; Ohman SC et al.; The purpose of this prospective study was to re-examine the relative importance of various factors in the pathogenesis of angular cheilitis . Sixty-four patients with cheilitis were examined clinically and microbiologically . In addition, a subsample of 23 patients was examined for serum iron and transferrin . The clinical appearance of the lip lesions fell into 4 categories . A ground rhagad at the corner of the mouth involving adjacent skin, was the most frequent type among dentate patients, whereas among denture wearers a deep lesion following the labial marginal sulcus was frequently observed . Dentate patients and denture wearers with cheilitis often had atopic constitution or cutaneous diseases . Pathogenic microorganisms were cultured from the lesions in all 64 patients; Staphylococcus aureus in 40 patients and Candida albicans in 45 . The results of this study indicate a correlation between angular cheilitis and pathogenic microorganisms . Furthermore, among dentate patients, a correlation exists between cutaneous discomfort and angular cheilitis . Other etiological factors suggested for this disorder were found to be of subordinate importance.

J Appl Bacteriol, 1986 Apr, 60(4), 319 - 25
Inhibition of hyphal development and kill of Candida albicans blastospores by noxythiolin in vitro; Gorman SP et al.; The cidal activity of the antimicrobial agent, noxythiolin, was investigated against a laboratory strain and a fresh isolate of Candida albicans . The order of resistance to noxythiolin was hyphal form (isolate) greater than or equal to 25 degrees C-grown blastospores (isolate) greater than 37 degrees C-grown blastospores (isolate) greater than laboratory strain blastospores . Noxythiolin activity was superior to that of 'equivalent' formaldehyde concentrations . Mycelial transformation in C . albicans was examined by light and scanning electron microscopy and measured in terms of percentage germination and hyphal extension . Noxythiolin, 2.5%, in contact for 30 min prevented germination of the blastospore population whereas the decomposition products, formaldehyde and N-methylthiourea, showed no appreciable effect in the expected concentrations . The implications of these results are discussed in relation to the observed clinical efficacy of noxythiolin.

Zh Mikrobiol Epidemiol Immunobiol, 1986 Apr, (4), 57 - 61
{Delayed hypersensitivity and nonspecific cellular immunity . The cytotoxic activity of macrophages, natural and antibody-dependent killer cells}; Gordienko SM; The experiment on (BALB/cXC57BL)F1 mice, showing a high level of delayed hypersensitivity (DH) when sensitized with BCG vaccine and Staphylococcus aureus strain B-243, has demonstrated the influence of such sensitization and DH reaction induced by the injection of a specific antigen (old tuberculin or staphylococcal phagolysate) into the sensitized animals on the cytotoxicity of macrophages, natural killers (NK) and antibody-dependent killers (ADK) . Sensitization with BCG vaccine alone results in an insignificant rise in the activity of these effector cells, and sensitization with S . aureus produces no changes at all . The pronounced activation of the cytotoxicity of macrophages, NK and, to a lesser extent, ADK has been observed in DH reaction induced by the injection of a specific antigen into the sensitized mice . In the course of DH reaction a rise in the activity of NK and ADK not only against tumor target cells, but also against microbial ones (Candida albicans and S . aureus) has been found to occur.

J Clin Hosp Pharm, 1986 Apr, 11(2), 117 - 23
A note on the recovery of micro-organisms from an oil-in-water cream; Brown MW et al.; The isolation of micro-organisms from the oil-in-water Aqueous Cream BP, has been examined using a variety of solvent systems to disperse the cream prior to membrane filtration or direct inoculation . Pour-plate methods which utilize combinations of either peptone-water (containing 5% w/v polysorbate 80) or nutrient broth (containing 4% w/v Lubrol W) provided the most efficient recovery of Pseudomonas aeruginosa but still allowed less than 20% recovery . White spirit and isopropyl myristate allowed no recovery when used as dispersants . Recoveries of P . aeruginosa varied according to the source of the cream . A combination of 1% w/v polysorbate 80 in 0.1% w/v peptone-water and membrane filtration allowed 63.2% w/v and 67.0% w/v recoveries respectively of Aspergillus niger and Candida albicans from unpreserved aqueous cream, but gave unreproducible results for Escherichia coli and P . aeruginosa . Chlorocresol 0.1% w/v) did not meet the British Pharmacopoeial requirements for efficacy of antimicrobial preservatives when tested against C . albicans using membrane filtration to isolate the micro-organism.

J Med Vet Mycol, 1986 Apr, 24(2), 133 - 44
Azole resistance in Candida albicans; Smith KJ et al.; An isolate of Candida albicans from a patient with chronic mucocutaneous candidosis who relapsed during ketoconazole treatment was compared with a number of other azole-sensitive and azole-resistant isolates by tests in vitro and in three animal models of vaginal or disseminated infection . In-vitro tests indicated that the isolate was cross-resistant to all imidazole and triazole antifungals tested . In the animal models, treatment with miconazole, ketoconazole, itraconazole or fluconazole failed to influence the infection.

Infect Immun, 1986 Apr, 52(1), 151 - 5
Mechanisms of killing of Toxoplasma gondii by rat peritoneal macrophages; McCabe RE et al.; Rats are resistant to Toxoplasma infection, and macrophages are thought to mediate this resistance . We performed a series of experiments to investigate the mechanism of the anti-Toxoplasma activity of resident rat peritoneal macrophages . Resident rat peritoneal macrophages killed more than 90% of ingested Toxoplasma gondii in vitro . This capacity was reduced progressively with the prolongation of culturing of macrophages in vitro before challenge with T . gondii . Exhaustion of the respiratory burst of macrophages with phorbol myristate acetate impaired their ability to kill and limit the replication of T . gondii . Histidine and diazabicyclooctane, presumed scavengers of singlet oxygen, were the only members of a battery of scavengers of metabolites of the respiratory burst that impaired the anti-Toxoplasma activity of macrophages . Ingestion of heat-killed Candida albicans by macrophages reduced large amounts of intracellular Nitro Blue Tetrazolium dye, whereas little dye was reduced by the ingestion of T . gondii . Challenge of macrophages with T . gondii released no detectable superoxide anion, as measured by the reduction of ferricytochrome c, whereas stimulation of macrophages with phorbol myristate acetate or ingestion of heat-killed Candida by macrophages released abundant superoxide anion . These data are consistent with the contributions of oxygen-dependent and oxygen-independent mechanisms to the anti-Toxoplasma activity of rat peritoneal macrophages . In addition, neonatal rats are known to be susceptible to Toxoplasma infection in vivo . However, resident neonatal rat peritoneal macrophages ingested and killed T . gondii to the same extent as did adult macrophages . Thus, the susceptibility of neonatal rats to Toxoplasma infection probably resides in other aspects of macrophage function or the immune response.

Int J Gynaecol Obstet, 1986 Apr, 24(2), 97 - 101
Antimicrobial properties of amniotic fluid from some Nigerian women; Ojo VA et al.; Fifty-one amniotic fluids were aspirated via the vaginal route from 51 pregnant Nigerian mothers . Their antimicrobial activity was tested against Staphylococcus aureus, Escherichia coli and Candida albicans . Inhibition rates were 39.2% for Staph . aureus 19.6% for E . coli and 41.2% for C . albicans . The overall inhibitory capacity was 64.7% . Sixteen fluids (31.4%) were active against one organism, three fluids (5.9%) were active against two organisms and one fluid (2%) was active against the three organisms . Age, parity and meconium-staining of liquor had no correlation with antimicrobial properties . The possible explanations for these are given.

Eur J Immunol, 1986 Apr, 16(4), 370 - 5
Antigen presentation by human monocytes: effects of modifying major histocompatibility complex class II antigen expression and interleukin 1 production by using recombinant interferons and corticosteroids; Rhodes J et al.; Lymphocyte proliferation in response to monocytes pulsed with an antigenic extract of Candida albicans was measured in vitro and the effects of modifying major histocompatibility complex (MHC) class II antigen expression at the surface of the antigen-presenting cells was investigated . The study shows that no simple correlation exists between changes in MHC class II antigen expression and changes in the effectiveness of antigen presentation . Recombinant interferon-alpha 1 (rIFN-alpha 1), rIFN-gamma and hydrocortisone were found to increase the expression of monocyte class II MHC antigens . In contrast, rIFN-alpha 2 did not increase class II antigen expression although it did increase MHC class I expression . Treatment of monocytes with rIFN-alpha 1, rIFN-alpha 2 or corticosteroids during antigen pulsing resulted in a reduction in the subsequent proliferative lymphocyte response . In all cases this inhibitory effect was restricted to antigen-specific proliferative responses since the polyclonal lymphocyte response to pokeweed mitogen-pulsed monocytes remained unaffected . Only rIFN-gamma treatment of antigen-pulsed monocytes resulted in enhancement of the subsequent specific lymphocyte proliferative response . The suppressive effects of hydrocortisone could not be attributed to its well documented inhibitory effects on arachidonic acid metabolism . The effect of C . albicans antigen, IFN and corticosteroids on interleukin 1 (IL 1) production by monocytes was also investigated . C . albicans antigen alone induced IL 1 production . So too did IFN-alpha 1 and IFN-gamma . IFN-alpha 2 did not induce IL 1 production . Addition of interferons together with C . albicans, however, resulted in the same level of IL 1 productions as with C . albicans antigen alone . Neither antigen nor IFN had any effect on IL 1 action in the thymocyte assay . Corticosteroids did not affect IL 1 production by monocytes but were potent antagonists of IL 1 in the thymocyte proliferation assay . Mitogen-induced thymocyte proliferation was also inhibited by corticosteroids . Pretreatment of monocytes with hydrocortisone followed by washing did not markedly affect their subsequent ability to produce IL 1 neither was it possible to reverse the inhibitory effects of hydrocortisone on antigen presentation by addition of exogenous IL 1 . Thus, signals which alter class II MHC antigen expression influence the antigen-presenting capacity of monocytes by a mechanism independent of IL 1 . No simple correlation exists between class II expression and antigen-presenting capacity.

Infect Immun, 1986 Apr, 52(1), 200 - 4
Increased susceptibility to lethal Candida infections in burned mice preinfected with Pseudomonas aeruginosa or pretreated with proteolytic enzymes; Neely AN et al.; Lethal Candida infections in burn patients are frequently preceded by or occur concomitantly with bacterial infections, which are often due to Pseudomonas aeruginosa . In this study, we developed a burned, mixed-challenge mouse model, which was designed to determine whether and how a recent bacterial infection could influence the development of subsequent candidosis . In this model, burned mice that were preinfected with a sublethal challenge of elastase-producing P . aeruginosa strain WR-5 and then sublethally challenged with Candida albicans exhibited a mortality rate of 60%, while unburned mice challenged in the same way and burned mice that received only one challenge organism exhibited mortality rates of less than 10% . Quantitative microbial counts performed with the kidneys, livers, and eschars of burned mice challenged with both organisms indicated that the deaths were due to Candida infection . Substitution of an elastase-negative P . aeruginosa strain for strain WR-5 in the model resulted in significantly lower mortality rates and lower microbial numbers in the organs . When the Pseudomonas enzyme elastase was substituted for the elastase-positive bacteria in the model, both the mortality rates and the organ counts were comparable to the values found after preinfection with strain WR-5 . Another protease, thermolysin, was substituted for the elastase and produced similar mortality results . When the protease inhibitor alpha 2-macroglobulin was given to burned mice infected with the two organisms, it prevented the deaths due to Candida infection . We concluded that this model is one way to study bacterial-fungal infections in burned mice, that recent Pseudomonas infections could predispose burned mice to fatal candidosis, and that the proteolytic activity generated by the bacteria was primarily responsible for the establishment of lethal fungal infections.

Am J Ophthalmol, 1986 Mar 15, 101(3), 288 - 93
Corneal biopsy in the diagnosis of keratomycosis; Ishibashi Y et al.; In two patients, a 55-year-old man and a 49-year-old man, who had fungal keratitis initially undiagnosed by corneal scrapings the condition was successfully diagnosed by corneal biopsy . We compared corneal biopsy specimens and corneal scraping in the diagnosis of keratomycosis in rabbits with experimental bilateral fungal keratitis caused by Fusarium solani, Aspergillus fumigatus, and Candida albicans . Corneal scrapings disclosed three specimens (30%) positive for Candida, five (50%) for Fusarium, and six (60%) for Aspergillus keratitis, whereas corneal biopsy specimens showed fungal elements of Fusarium, Aspergillus, and Candida in all inoculated eyes.

Biochem J, 1986 Mar 15, 234(3), 543 - 6
A cyclic AMP-independent protein kinase from Candida albicans; Gupta Roy B et al.; A cyclic AMP-independent protein kinase which phosphorylates casein was purified to homogeneity from Candida albicans by affinity and ion-exchange chromatography . This protein kinase exhibits maximal activity with casein as substrate and is not stimulated by cyclic AMP or cyclic GMP . The Mr of the purified enzyme is 115,000, as determined by h.p.l.c . It migrates as a single band on gel electrophoresis and has three non-identical subunits, of Mr 44,000, 28,500 and 26,000, as determined by SDS/polyacrylamide-gel electrophoresis . This enzyme is insensitive to heparin, but is inhibited by polyamines . Furthermore, it is sensitive to thermal denaturation and to thiol reagents.

Acta Chir Scand, 1986 Mar, 152, 175 - 9
Influence of surgery, age and serum albumin on delayed hypersensitivity; Hjortso NC et al.; Delayed hypersensitivity was assessed with four antigens, viz . purified protein derivative of tuberculin (PPD), Candida albicans, streptokinase/streptodornase and mumps, 48 hours before and 24 hours after elective major abdominal surgery in 24 patients . Cumulated areas of skin response were recorded on the basis of readings 24 and 48 hours after antigen stimulation . A control group of 16 patients was similarly assessed, but without surgery between the two test occasions . Retesting in this control group increased the cumulated skin response area in all patients . The respective means for the two tests were 1 290 +/- 222 to 2 330 +/- 365 mm2 (p less than 0.0001), demonstrating a pronounced booster action by the initial test . In contrast, the surgical patients showed a decrease, from 1 559 +/- 203 preoperatively to 1 230 +/- 210 mm2 postoperatively (p = 0.14) . The postoperative response was significantly lower than the retesting response in the controls without surgery (p = 0.02), indicating that surgery leads to depression of delayed hypersensitivity response . The preoperative cumulated skin test response correlated with age (r = -0.66, p less than 0.001) and with serum albumin (r = 0.59, p less than 0.01) . Postoperative depression of the skin test response also was related to age (r = 0.53, p less than 0.01) and with postoperative fall in s-albumin (r = 0.51, p less than 0.05) . The results emphasize that interpretation of serial skin testing in surgical patients is not adequate unless comparison is made with a similar retesting regimen in nonsurgical patients.

J Antimicrob Chemother, 1986 Mar, 17(3), 361 - 3
Prophylaxis of Candida albicans infection with tuftsin; Nishioka K et al.; The efficacy of tuftsin, a naturally-occurring immunomodulating peptide, in the prophylaxis of disseminated Candida albicans infections in mice was studied . The intravenous administration of tuftsin caused prolonged survival at all concentrations tested.

Antimicrob Agents Chemother, 1986 Mar, 29(3), 389 - 94
Synergistic action of nikkomycins X and Z with papulacandin B on whole cells and regenerating protoplasts of Candida albicans; Hector RF et al.; Combinations of nikkomycin X (NX) or nikkomycin Z (NZ), known inhibitors of chitin synthesis in fungi, together with papulacandin B (PB), an inhibitor of beta-glucan synthesis, were tested for synergistic activity against four isolates of Candida albicans by using the broth microdilution checkerboard technique and a method to assess the regeneration of cell wall material in protoplasts . The construction of isobolograms from the data generated by the checkerboard determinations revealed a synergistic effect for the two classes of compounds against all strains . The combination of NX and PB was more effective than the combination of NZ and PB, perhaps reflecting the lower Ki value of NX . While the presence of NX and NZ reduced chitin synthesis, as determined by staining with calcofluor white and assaying with a microfluorimeter, cells treated with PB demonstrated an increased synthesis of chitin . Protoplast regeneration experiments using similar concentrations of the two classes of compounds resulted in comparable findings . The combination of NX and PB resulted in a greater inhibition of chitin synthesis than did equivalent combinations of NZ and PB . These data suggest that combinations of agents active against cell wall synthesis in fungi may prove more useful as chemotherapeutic agents than such compounds used singly.

Mycopathologia, 1986 Mar, 93(3), 189 - 92
Effects of a new pyrazolo {3, 4-d}pyrimidine on growth and morphology of Candida albicans; Califano A et al.; A new pyrazolo {3, 4-d}pyrimidine derivative was synthesized and its antifungal activity evaluated in vitro against mycelial and yeast cells of Candida albicans . The most striking ultrastructural changes following treatment with 10-30 micrograms/ml (mycelia) and 25-75 micrograms/ml (yeasts) consisted in the deterioration of the organelle membranes and in aberrant thickenings of the cell wall . The complete disorganization of the cytoplasmic structures seemed to be the final event.

Mycopathologia, 1986 Mar, 93(3), 147 - 50
Induction of the immune response suppression in mice inoculated with Candida albicans; Valdez JC et al.; There is a controversy in respect to the immunological response (humoral or cellular) concerning the defense against Candida albicans . Candidosis would induce sub-populations of suppressor cells in the host cell-immune response . This report tries to show the effect of different doses of C . albicans (alive or heat-killed) on the expression of cell-mediated and humoral immunity . The effect upon cell immunity was determined by inoculating different lots of singeneic mice, doses of varied concentration of C . albicans and checking for delayed-type hipersensitivity (D.T.H.) . D.T.H . was also controlled in syngeneic normal mice which had previously been injected with inoculated mice spleen cells . Humoral immunity was assayed by measuring the induced blastogenesis by Pokeweed Mitogen on spleen mononuclear cells with different doses of C . albicans . Results obtained show that the different doses gave origin to: Suppression of humoral and cell response (10(8) alive); Suppression of only humoral response (10(6) alive); Suppression of cell response and increase of humoral response (10(9) dead); Increase of both responses (10(8) dead).

J Clin Lab Immunol, 1986 Mar, 19(3), 127 - 33
Pulmonary defence mechanism in mice . A comparative role of alveolar macrophages and polymorphonuclear cells against infection with Candida albicans; Lal S et al.; The protective roles of alveolar macrophages and polymorphonuclear cells were analyzed against intratracheal challenge with Candida albicans in mice . When mice were treated with carrageenan, a known cytotoxic agent for macrophages, there was no change in susceptibilities to the challenge in terms of the survival and the progressive elimination of fungi from the lung and kidney, in spite of a decreased in vitro phagocytosis of Candida albicans by their alveolar macrophages . On the other hand, irradiated mice (whole body irradiation with 800 rads) showed an enhanced mortality and a progressive growth of Candida albicans in their lungs and kidneys, although no change was observed in the in vitro phagocytic activity of alveolar macrophages until day 6 after irradiation . In normal and carrageenan treated mice, there was a progressive increase in the recruitment of polymorphonuclear cells into the lung after the challenge as shown by bronchoalveolar lavage and histological examination . In irradiated mice, on the other hand, there was a decreased recruitment of polymorphonuclear cells at 24 hr after the challenge, and a complete impairment at a late stage . When phagocytes were obtained from normal mice and examined for in vitro phagocytic activity to Candida albicans, polymorphonuclear cells showed higher activity than that of alveolar macrophages . These results suggest that polymorphonuclear cells play a very important role in the protection against intratracheal infection with Candida albicans.

Eur J Respir Dis, 1986 Mar, 68(3), 200 - 6
Association of defective monocyte chemotaxis with recurrent acute exacerbations in chronic obstructive lung disease; Nielsen H et al.; Since mononuclear phagocytes are crucial in resisting microbial challenge in the lung, selected functions of blood monocytes were studied in 27 patients with chronic bronchitis (19 with hypersecretory symptoms and many acute infectious exacerbations and eight with obstructive symptoms without recurrent infections), and compared with 82 healthy controls . While monocytes from patients with solely obstructive symptoms had a normal migratory function, both spontaneous and chemotactic migration were depressed in the patients with hypersecretory symptoms . Phagocytic activity of the blood monocytes was equally depressed in both subgroups . Intracellular killing of Candida albicans was normal in all patients when compared with smoking control subjects . Chemotactic responsiveness was thus decreased only in patients with hypersecretory symptoms, suggesting that a defect in monocyte migration in these patients might contribute to the high incidence of acute bronchial exacerbations.

J Clin Microbiol, 1986 Mar, 23(3), 568 - 75
Enzyme-linked immunosorbent assay measurement of fluctuations in antibody titer and antigenemia in cancer patients with and without candidiasis; Fujita S et al.; Antibody titers against purified sulfate-soluble fraction (PSSF) obtained from cytoplasmic extracts of Candida albicans were determined retrospectively over a 2-year period for 123 cancer patients by enzyme-linked immunosorbent assay . Antibody against cell wall mannan (CWM) was also measured by the hemagglutination test and the production of precipitins by a serum interacting with a yeast cell homogenate by immunodiffusion . Invasive candidiasis determined by histological evidence at autopsy was present in 10 patients . Fourfold or greater rises in anti-CWM and anti-PSSF antibodies were detected for eight of the patients with invasive candidiasis at 14 to 22 days after the onset of fever . The immunodiffusion test was positive for four patients with invasive candidiasis . For patients with no evidence of candidiasis, significant rises in anti-CWM and anti-PSSF antibodies were observed at a frequency of 20 and 10%, respectively . The concentrations of serum mannan were sequentially measured by the enzyme-linked immunosorbent assay . Antigenemia (greater than or equal to 3 ng/ml) was found in 9 of the 10 patients with invasive candidiasis and in 2 of the 4 patients with thrush, whereas the serum of 1 of the 36 patients with no evidence of candidiasis was positive for antigen . The first antigenemia antedated significant rises in antibody levels against Candida species by 6 to 23 days.

Methods Find Exp Clin Pharmacol, 1986 Mar, 8(3), 163 - 6
Modulatory effect of glucans on the functional and biochemical activities of guinea-pig macrophages; Ferencik M et al.; The particulate and soluble glucan preparations isolated from Saccharomyces cerevisiae and Candida albicans affected various activities of guinea-pig macrophages . The stimulation of INT reduction and superoxide production were observed in the presence of all insoluble and some soluble glucans in vitro, but most of the preparations under study had an inhibitory effect on phagocytic activity . On the other hand, the stimulation of both metabolic and functional activities was obtained in vivo . Macrophages from guinea-pigs treated with glucans exerted an increased ability to reduce INT and to produce superoxide . Their candidacidal capacity was rapidly elevated, and peritoneal macrophages had raised phagocytic activity as well . A more pronounced stimulatory effect was observed in the presence of insoluble rather than soluble glucans, and this was more expressive in vitro than in vivo.

Infect Immun, 1986 Mar, 51(3), 731 - 5
Inhibition of neutrophil killing of Candida albicans pseudohyphae by substances which quench hypochlorous acid and chloramines; Wagner DK et al.; Using a microtiter plate killing assay, we investigated the in vitro killing of Candida albicans by human neutrophils and by hypochlorous acid/hypochlorite ion (HOCl/OCl-) or chloramine solutions to evaluate the inhibition of this process by quenchers of these oxidants . Methionine, tryptophan, and alanine were able to effectively inhibit neutrophil killing of candida pseudohyphae . These substances were capable of quenching the oxidant activity of NaOCl, monochloramine (NH2Cl), and to a lesser extent, taurine chloramine . NaOCl and NH2Cl were able to kill C . albicans in the absence of inhibitors in concentrations of less than 5 microns M, whereas greater than 100 microns M taurine chloramine was required for killing . Methionine and tryptophan were capable of markedly inhibiting killing by all three oxidants, whereas alanine affected only killing by NaOCl . The oxidant activity of NaOCl was more readily quenched by opsonized or unopsonized Candida yeast than was the oxidant activity of either NH2Cl or taurine chloramine . These results suggest that some substances which quench the oxidizing activity of the products of the neutrophil myeloperoxidase system can inhibit the killing of C . albicans by these cells.

Antibiot Med Biotekhnol, 1986 Mar, 31(3), 218 - 20
{Sensitivity of fungi in the genus Candida to antimicrobial preparations}; Palii GK et al.; Sensitivity of 50 Candida fungus strains isolated from patients with chronic intestine diseases was studied with respect to amphotericin B, levorin, enteroseptol, intestopan and decamethoxin . The rate of forming resistant variants of the strains with respect to decamethoxin and development of their cross resistance to levorin was estimated . It was shown that decamethoxin was the most active antifungal drug among the drugs tested . Estimation of sensitivity of the Candida strains to enteroseptol and intestopan revealed that the fungicidal concentration of enteroseptol for 78 per cent of the strains ranged within 3.9-7.8 micrograms/ml . It was demonstrated that development of resistance to decamethoxin in the strains of Candida albicans was slow and did not reach high levels . No cross resistance between decamethoxin and levorin was detected.

Ann Inst Pasteur Immunol, 1986 Mar-Apr, 137C(2), 117 - 25
Production and partial characterization of anti-Candida monoclonal antibodies; Chardes T et al.; Spleen cells of Biozzi HR mice immunized with formolized, lyophilized Candida albicans serotype A cells were fused with P3-X63-Ag8.653 mouse myeloma cells . Twenty-one monoclonal antibodies (mAb) selected by an indirect ELISA technique were produced and partially characterized . All mAb reacted with a C . albicans cell wall extract . Five of the mAb were directed against C . albicans serotype A, but not against serotype B . These mAb also recognized C . tropicalis . The 16 other mAb cross-reacted with several yeast species . The immunoreactivity profiles of 5 representative anti-Candida mAb were confirmed in most cases by inhibition studies.

Exp Hematol, 1986 Mar, 14(3), 241 - 5
Effect of cytosine arabinoside on differentiation of normal human bone marrow cells; Nagler A et al.; Human normal bone marrow cells were evaluated for alteration of differentiation after exposure for seven days to 10(-12)-10(-9) M cytosine arabinoside (ARA-C) in liquid culture . An increased number of induced cells had the morphologic appearance of mature monocytes-macrophages; they adhered to petri dishes, reacted positively to fluoride-sensitive naphthyl acetate esterase, and specifically bound My4 monoclonal antibody (MCAb) . Assessment of phagocytosis and killing of Candida albicans (CA) by cultured monocytes-macrophages exposed to ARA-C demonstrated that treated cells had the same capacity to phagocytose and kill CA as did untreated cells . In semisolid culture, low doses of ARA-C did not affect myeloid colony growth . These studies indicate that ARA-C enhances monocytic differentiation of normal human bone marrow cells in liquid culture.

Biochim Biophys Acta, 1986 Feb 24, 866(1), 26 - 31
A novel suppressor tRNA from the dimorphic fungus Candida albicans; Tuite MF et al.; Unfractionated tRNAs from a number of prokaryotes and eukaryotes were examined for their ability to promote termination codon readthrough in a cell-free system isolated from Saccharomyces cerevisiae . tRNA from the dimorphic fungus Candida albicans was found to have significant UGA and UAG readthrough activity and this activity was present in tRNA extracted from both the yeast and the hyphal phase of the fungus . Unusually the efficiency of readthrough activity in vitro was not affected by the {psi} determinant . C . albicans tRNA was fractionated by one-dimensional and two-dimensional gel electrophoresis and both readthrough activities appeared to be associated with a single species of tRNA.

Immun Infekt, 1986 Feb, 14(1), 24 - 5
{Effect of the cephalosporin derivative cefodizime on the immune system in in vivo experiments}; Hanel H; In various infection models with the pathogenic yeast Candida albicans, Cefodizime influences the development of the infection . Although it does not exhibit any fungicidal or fungistatic action it decreases the number of yeast cells or prolonges survival.

Am J Kidney Dis, 1986 Feb, 7(2), 153 - 6
An animal model for fungal peritonitis: evaluation of therapeutic options; Ahmad S et al.; An animal model for fungal peritonitis was developed and is described . This model was used to compare various therapeutic options for Candida albicans peritonitis . Twenty-four rabbits were treated on three different protocols . Results from these protocols confirm the clinical observation that removal of the catheter is necessary for successful treatment of fungal peritonitis . Further, the combination of catheter replacement and imidazole anti-fungal therapy appears to be curative in this animal model, and suggests that by using this protocol, discontinuation of peritoneal dialysis may not be necessary.

Infect Immun, 1986 Feb, 51(2), 668 - 74
Evidence for macrophage-mediated protection against lethal Candida albicans infection; Bistoni F et al.; Systemic infection of mice with a Candida albicans strain (PCA-2) incapable of yeast-mycelial conversion conferred protection against a subsequent intravenous challenge with the pathogenic strain of the parent organism, strain CA-6 . Protection was nonspecific since it was also detected upon challenge of mice with Staphylococcus aureus . Moreover, the PCA-2 organisms had to be viable, their effects being most evident when they were given intravenously at a dose of 10(6) cells 7 to 14 days prior to microbial challenge . Thus, all mice pretreated with PCA-2 and challenged 14 days later with viable CA-6 cells lived through a 60-day observation period, whereas all control mice not treated with PCA-2 died within 3 days . In an attempt to correlate the immunostimulatory effects observed in vivo with possible modifications in in vitro functions, it was found that administration of PCA-2 was accompanied by an increase in the number of peripheral blood polymorphonuclear cells and by the activation in the spleen of cells with highly candidacidal activity in vitro . Moreover, the adoptive transfer of plastic-adherent cells from PCA-2-infected mice into histocompatible recipients conferred considerable protection against subsequent CA-6 challenge.

Antimicrob Agents Chemother, 1986 Feb, 29(2), 303 - 8
A 19F nuclear magnetic resonance study of uptake and metabolism of 5-fluorocytosine in susceptible and resistant strains of Candida albicans; Di Vito M et al.; The metabolism of the antifungal drug 5-fluorocytosine (5-FC) was studied in intact viable cells of Candida albicans by 19F nuclear magnetic resonance (NMR) . The uptake of the drug and its conversion to the deaminated product 5-fluorouracil (5-FU) were easily observed by NMR analysis of both the cells and the supernatants of the incubation mixture . In the 5-FC-resistant mutant D14 of C . albicans, which lacked cytosine deaminase activity, the resonance peak of 5-FU was not observed . In intact cells of all 5-FC-susceptible strains the metabolism of 5-FU progressed to the formation of other fluorinated derivatives which were visualized as a single, broad resonance band at a lower field with respect to 5-FC and 5-FU . This band was resolved into three distinct peaks in the acid extract of treated cells, one of these peaks being attributable to 5-fluoro-dUMP (5-FdUMP) . In strain 72R of C . albicans, which is 5-FC resistant because of a low level of UMP-pyrophosphorylase activity, the broad, low-field resonance band was detected later and with much less intensity than in the 5-FC-sensitive strains . This suggests that, besides 5-FdUMP, this band is also contributed to by 5-FUMP and possibly other phosphorylated derivatives . 19F NMR analysis also revealed that a significant amount of 5-FU is secreted into the external medium, the rate of secretion being higher in 5-FC-resistant strain 72R than in 5-FC-sensitive strain 72S . Although not all resonances were definitely identified, this study shows that 19F NMR spectroscopy may be an important tool for noninvasive analysis of the metabolism of fluorinated drugs in yeasts.

Mycopathologia, 1986 Feb, 93(2), 121 - 6
Ultrastructural study of Candida albicans yeast after application of a ribonuclease; Moulin-Traffort J et al.; Electron microscopy was performed on Candida albicans yeast after application of ribonuclease to clear the cytoplasmic background . In conjunction with Thiery's method of highlighting polysaccharide components, this clearing technique, which has not been used since 1959, enabled visualization of the nucleus, the mitochondria, the vacuolar system and another structure which seemed to be the Golgi apparatus . The invaginations of the plasmalemma membrane (or lomasomes) are highly developed and may be partially responsible for transporting material required for development of the cell wall, especially during budding.

J Gen Microbiol, 1986 Feb, 132 ( Pt 2), 443 - 53
Occurrence of ploidy shift in a strain of the imperfect yeast Candida albicans; Suzuki T et al.; A clinical isolate of Candida albicans, a member of the Fungi Imperfecti, was polyploid as shown by the fact that it contained two kinds of nuclei, one of diploid and one of tetraploid DNA content . These determinations were made by fluorescence microscopy-photometry . The nucleus-associated organelles (NAOs), or spindle pole bodies, of yeast cells in this isolate were classified into two groups, one diploid and the other tetraploid, according to their dimensions as determined by serial thin-sectioning electron microscopy . A ploidy shift from diploid to tetraploid was found in individual cells of a culture of this isolate undergoing diphasic growth in minimal salts medium . A process of shift-down or reduction of ploidy from tetraploid to diploid was also observed by electron microscopy during these growth conditions: this appeared to occur in large cells which showed multiple spindle formation during nuclear division, a phenomenon apparently similar to the process of meiosis II during sporogenesis of Saccharomyces cerevisiae, but differing in that it produces diploid daughter nuclei by the vegetative process.

J Gen Microbiol, 1986 Feb, 132 ( Pt 2), 263 - 8
Arginine auxotrophs of Candida albicans deficient in argininosuccinate lyase; Gibbons GF et al.; Auxotrophic mutants of Candida albicans FC18 were induced by a combination of treatments with nitrous acid and UV irradiation . Arginine (Arg-), histidine (His-) and methionine/cysteine (MetA-) auxotrophs were recovered by this means . The Arg- auxotrophs lacked active argininosuccinate lyase (EC 4.3.2.1), the enzyme catalysing the final step in arginine biosynthesis . Thus the locus may be designated arg-4 . The mutant strains bearing this mutation did not form germ tubes unless the germination medium contained arginine.

J Clin Microbiol, 1986 Feb, 23(2), 298 - 301
Results of a survey of antifungal susceptibility tests in the United States and interlaboratory comparison of broth dilution testing of flucytosine and amphotericin B; Calhoun DL et al.; In a survey of 350 laboratories, 41 of 210 respondents indicated that they performed antifungal susceptibility tests . Two-thirds performed 20 or fewer tests per year, and most used a broth dilution method to test amphotericin B and flucytosine activity against Candida albicans . The broth dilution procedure of S . Shadomy and A . Espinel-Ingroff (p . 647-653, in E.H . Lennette, ed., Manual of Clinical Microbiology, 3rd ed., 1980) was the method most frequently cited, and therefore this method was used to test the susceptibility of five isolates of C . albicans and one of Saccharomyces cerevisiae to amphotericin B and flucytosine in seven research laboratories . Agreement among replicates performed on the same day by each laboratory was excellent for both drugs, all values being within 1 twofold drug dilution . Precision from week to week for each laboratory was also good, with 95 and 92% of values being within 1 drug dilution for amphotericin B and flucytosine, respectively . Interlaboratory precision, however, was poor . For amphotericin B, values varied 8- to 32-fold, and for flucytosine, they varied 32- to greater than 512-fold . We conclude that antifungal susceptibility testing is currently being performed in small volumes by numerous laboratories in the United States and that results from one laboratory may not agree with results from another . Improved standardization of fungal susceptibility tests is necessary before their results can be generally applied to clinical situations.

Eur J Clin Microbiol, 1986 Feb, 5(1), 103 - 9
Serum fungistatic and fungicidal activity in volunteers receiving antifungal agents; Meunier F; The serum levels of two imidazoles, ketoconazole and Bayer n7133, when administered alone or in combination with rifampin, were measured in volunteers and the serum antifungal activity was determined against various fungal strains . Serum levels were measured by high pressure liquid chromatography and correlated with serum fungistatic activity as determined in microtiter plates . Ketoconazole showed a wide range of serum levels, suggesting individual variations . The addition of two doses of rifampin significantly decreased serum levels of both imidazoles and no synergism was observed . Serum fungicidal activity could only occasionally be demonstrated against one strain of Candida albicans and Candida stellatoidea . Serum fungistatic activity significantly correlated with the serum levels of both imidazoles . This approach should be investigated in patients to establish its potential clinical relevance for managing invasive fungal infections.

J Reprod Med, 1986 Feb, 31(2), 131 - 2
Three-day treatment with butoconazole vaginal suppositories for vulvovaginal candidiasis; Adamson GD et al.; Butoconazole is a new imidazole, effective as therapy for vulvovaginal candidiasis for women who prefer solid-type vaginal preparations . The efficacy of three-day administration of butoconazole vaginal suppositories, 100 mg/day, was compared to that of clotrimazole vaginal tablets, 200 mg/day . Patients with culture-proven vulvovaginal candidiasis were randomly assigned to either butoconazole (97 patients) or clotrimazole (88 patients) . The percentage of patients with fungal cultures negative for Candida albicans was statistically significantly higher for butoconazole than for clotrimazole (92 vs . 74, P = .003) at the eight-day posttreatment examination . At the 30-day posttreatment examination the cure rate was still higher for butoconazole (63%) than for clotrimazole (56%), but the difference was not statistically significant . Complete clinical relief was achieved in 81% of patients in both treatment groups achieved in 81% of patients in both treatment groups at the first follow-up examination, while at the second follow-up examination the clinical cure rate was 77% for butoconazole and 69% for clotrimazole . No systemic side effects were reported.

J Hyg (Lond), 1986 Feb, 96(1), 89 - 93
The frequency distribution and consistency of assimilation biotypes of Candida albicans; Hellyar AG; Two hundred and fifty clinical strains of Candida albicans and six isolates from a cross-infection outbreak were studied for their ability to assimilate 19 carbohydrates in the API-20C system (APILaboratory Products Ltd., Basingstoke, UK) . The assimilation profiles were stable on repeat testing; at intervals in the 72 h duration of the test; and when incubated at different temperatures . Although not a complete system of biotyping, the API-20C system shows high typability, and fair reproducibility and discrimination, having a limited role in indicating which isolates should be typed by more elaborate methods.

Gastroenterology, 1986 Feb, 90(2), 443 - 5
Ketoconazole-resistant Candida esophagitis in patients with acquired immunodeficiency syndrome; Tavitian A et al.; Although ketoconazole has been shown to be effective in treating esophageal candidiasis in other immunodeficiency states, similar studies have not been reported in patients with acquired immunodeficiency syndrome . Six patients with acquired immunodeficiency syndrome and oral and esophageal candidiasis who had been treated with ketoconazole for more than 2 mo were evaluated with barium esophagram and endoscopy with biopsy and brush cytology . All of the patients had persistent Candida esophagitis . In 2 patients, fungal cultures and sensitivity testing indicated Candida albicans resistant to ketoconazole in vitro . In patients with acquired immunodeficiency syndrome, esophageal candidiasis may not resolve with up to 6 mo of ketoconazole therapy and may require more vigorous antifungal therapy than in patients with other immunodeficiency states.

Clin Exp Immunol, 1986 Feb, 63(2), 478 - 84
Neutrophil phagocytosis and killing in insulin-dependent diabetes; Wilson RM et al.; Neutrophil phagocytosis and killing of Candida albicans were examined using a radiometric assay in 25 patients with insulin-dependent diabetes and 17 controls under various in vitro metabolic conditions . Glucose was present at 5, 10 and 50 mM, beta-hydroxybutyrate at 1, 5 and 20 mM and glucose with beta-hydroxybutyrate in combinations of 10 with 5 and 50 with 20 mM, respectively . Phagocytosis occurred at similar levels in diabetics and controls at all the glucose and beta-hydroxybutyrate concentrations used . The ability to neutrophils from diabetics to kill candida was inhibited by increased concentrations of glucose and beta-hydroxybutyrate, both independently and in combination . Candida killing (mean +/- s.e.) was 20 +/- 2.4, 19 +/- 2.3 and 13 +/- 2.7% at glucose concentrations of 5, 10 and 50 mM; and 20 +/- 3.4, 20 +/- 3 and 13 +/- 3% at beta-hydroxybutyrate concentrations of 1, 5 and 20 mM, respectively, and in glucose and beta-hydroxybutyrate combinations of 10 with 5 and 50 with 20 mM was 20 +/- 2.8 and 10 +/- 2.8%, respectively . Inhibition was not observed with control neutrophils . These data indicate that although phagocytosis occurs at similar levels in diabetics and controls, killing of candida by the diabetic neutrophil is impaired under conditions of hyperglycaemia and ketosis . The biochemical basis for this effect is discussed.

J Immunol, 1986 Feb 1, 136(3), 837 - 43
Organ-associated macrophage precursor activity: isolation of candidacidal and tumoricidal effectors from the spleens of cyclophosphamide-treated mice; Baccarini M et al.; We recently reported the modulating effects of a single injection of the anti-neoplastic drug cyclophosphamide (Cy; 150 mg/kg i.p.) on in vivo resistance against the experimental Candida albicans infection . Increased resistance to microbial challenge occurred 12 to 18 days after treatment . We now show that the increased resistance is paralleled by the appearance of potent nonadherent nonphagocytic effectors in the spleen (day 12) that are capable both of candidacidal activity and natural killer (NK) activity against YAC-1 cells . The cells mediating the two reactivities have a low buoyant density, a strong proliferating activity in response to the macrophage colony stimulating factor (CSF-1), and are unable to kill the NK-insensitive lines EL-4 and P815 . A clear cut isolation of macrophage precursor cells from this Percoll low density fraction has been performed in an indirect rosette assay on the basis of their positivity for the surface markers recognized by the highly specific rat-anti-mouse macrophages, monoclonal antibodies M143 and F4/80 . We obtained an extremely homogeneous population of cells in the early stage of macrophage differentiation that is responsible for all the candidacidal activity and for a major part of the NK activity observed in the spleen of Cy-treated mice, and which is extremely sensitive to CSF-1 induction.

Am J Kidney Dis, 1986 Feb, 7(2), 146 - 52
Intracellular survival of Candida albicans in peritoneal macrophages from chronic peritoneal dialysis patients; Peterson PK et al.; Candidal peritonitis is a tenacious infection in patients undergoing chronic peritoneal dialysis . Since little is known about host defenses of the human peritoneal cavity against fungi, we investigated the interaction of peritoneal macrophages (PM phi) from uninfected dialysis patients with Candida albicans blastospores . Chemiluminescence (CL) techniques were used to assess the respiratory burst activity of these cells, and candidacidal activity was evaluated with a fluorochrome microassay . In sharp contrast to peripheral blood polymorphonuclear leukocytes (PMNs) from healthy donors, which gave a brisk luminol-enhanced CL response to opsonized blastospores and killed 35% of cell-associated organisms, PM phi produced barely detectable luminol-enhanced CL and killed only 13% of intracellular Candida . These findings appeared to be associated with a decreased level of myeloperoxidase in PM phi . The mechanism of intracellular survival of C albicans also appeared to be related to relatively poor triggering of superoxide production during phagocytosis of viable blastospores . The CL response of PMNs to C albicans was opsonin-dependent, and peritoneal dialysis effluent was devoid of opsonic activity . These studies suggest that local cellular and humoral mechanisms of defense are inadequate for protection of peritoneal dialysis patients against candidal peritonitis.

Obstet Gynecol, 1986 Feb, 67(2), 229 - 37
Preterm labor associated with subclinical amniotic fluid infection and with bacterial vaginosis; Gravett MG et al.; Maternal genital infection, particularly subclinical amniotic fluid infection, may cause preterm labor and a premature delivery . The prevalence of subclinical amniotic fluid infection was studied in 54 consecutive afebrile women in preterm labor with singleton gestations and intact fetal membranes . Microorganisms were recovered from the amniotic fluid by transabdominal amniocentesis in 13 (24%) of 54 patients . Bacteria or Candida albicans were recovered from six (11%), and genital mycoplasmas from seven (13%) . Compared with women with sterile amniotic fluid, patients whose amniotic fluid contained bacteria or Candida organisms had a shorter interval from onset of preterm labor until delivery (0.6 versus 34.3 days, P less than .01), were less responsive to tocolytic therapy (0 versus 81% success rate, P less than .005), and more frequently developed subsequent intrapartum fever (83 versus 2.4%, P less than .005) . In contrast, women whose amniotic fluid contained genital mycoplasmas did not differ in these parameters from those with sterile fluid . Also compared was cervical-vaginal infection among these patients in preterm labor with matched control subjects without preterm labor . In this analysis, bacterial vaginosis was identified in 43% of patients with and 14% of women without preterm labor (P = .02), yielding a relative risk of preterm labor for patients with bacterial vaginosis of 3.8 . These data underscore the importance of amniotic fluid bacterial infections in preterm labor and premature delivery, and suggest that bacterial vaginosis is associated with prematurity.

J Clin Microbiol, 1986 Feb, 23(2), 366 - 8
Specific and common antigenic determinants of Candida albicans isolates detected by monoclonal antibody; Polonelli L et al.; We isolated a hybridoma cell line which produced monoclonal antibody to one determinant of an exoantigen of Candida albicans . The immunoglobulin G antibody product was characterized by using a Western blot technique and was used for a serological analysis of numerous homologous and heterologous yeast isolates . Based on specific immunologic determinants, C . albicans strains were identified and clustered into five groups . The monoclonal antibodies were effective reagents for identifying and serotyping our C . albicans isolates; they have potential application in the epidemiology of yeast infections.

Infect Immun, 1986 Feb, 51(2), 712 - 4
Effects of dexamethasone on human natural killer cell cytotoxicity, interferon production, and interleukin-2 receptor expression induced by microbial antigens; Piccolella E et al.; Dexamethasone inhibits the expression of the interleukin-2 receptor, the synthesis of immune interferon, and the development of natural killer cells when added to peripheral blood mononuclear cells cultured with soluble microbial antigens (purified protein derivative and a polysaccharide extract from Candida albicans {MPPS}) or human recombinant interleukin-2.

J Biol Chem, 1986 Jan 25, 261(3), 1177 - 82
The primary structure and functional characterization of the neutral histidine-rich polypeptide from human parotid secretion; Oppenheim FG et al.; The neutral histidine-rich polypeptide (HRP) from human parotid secretion was isolated by ion-exchange and gel-filtration chromatography . The complete amino acid sequence determined by automated Edman degradation of the protein, tryptic and Staphylococcus aureus V8 protease peptides, and digestion with carboxypeptidase A is: (Formula: see text) where Pse represents phosphoserine . The polypeptide contains 38 residues and has Mr 4929 . The charged amino acids predominate with 7 histidine, 4 arginine, 3 lysine, 3 aspartic acid, 3 glutamic acid residues, and 1 phosphoserine . Assuming minimal charge contributions from histidine and one negative charge from phosphoserine at pH 7, the net charge of HRP is balanced by an equal contribution of basic and acidic residues . Furthermore, the distribution of hydrophilic and hydrophobic residues along the polypeptide chain indicates that there is no structural polarity . The polypeptide lacks threonine, alanine, valine, cysteine, methionine, and isoleucine . HRP did not display sequence similarity with any protein sequence in the National Biomedical Research Foundation Data Bank . HRP is an active inhibitor of hydroxyapatite crystal growth from solutions supersaturated with respect to calcium phosphate salts and therefore must play a role in the stabilization of mineral-solute interactions in oral fluid . In addition, HRP is a potent inhibitor of Candida albicans germination and therefore may be a significant component of the antimicrobial host defense system in the oral cavity.

Eur J Biochem, 1986 Jan 15, 154(2), 375 - 81
The isolation of plasma membrane and characterisation of the plasma membrane ATPase from the yeast Candida albicans; Hubbard MJ et al.; Plasma membrane ghosts were isolated from Candida albicans ATCC 10261 yeast cells following stabilisation of spheroplasts with concanavalin A, osmotic lysis and Percoll density gradient centrifugation . Removal of extrinsic proteins with NaCl and methyl alpha-mannoside gave increased ATPase and chitin synthase specific activities in the resultant plasma membrane fraction . Sonication of this fraction yielded unilamellar plasma membrane vesicles which exhibited ATPase and chitin synthase specific activities of 4.5-fold and 3.0-fold, respectively, over those of the plasma membrane ghosts . ATPase activity in the membrane ghosts was optimal at pH 6.4, showed high substrate specificity (for Mg X ATP) and was inhibited 80% by sodium vanadate but less than 4% by oligomycin and azide . The effects of a range of other inhibitors were also characterised . Temperature effects of ATPase activity were marked, with a maximum at 35 degrees C . Breaks in the Arrhenius plot, at 12.2 degrees C and 28.9 degrees C, coincided with endothermic heat flow peaks detected by differential scanning calorimetry . ATPase was solubilised from the plasma membranes with Zwittergent in the presence of glycerol and phenylmethylsulphonyl fluoride and partially purified by glycerol density gradient centrifugation . The solubilised enzyme hydrolysed Mg X ATP at Vmax = 20 mumol X min-1 X mg-1 in the presence of phospholipids, with optimal activity at pH 6.0--6.5.

Mycopathologia, 1986 Jan, 93(1), 61 - 3
Antifungal activity of some mediterranean algae; Calvo MA et al.; The antifungal activity of 15 mediterranean algae species on some dermatophyte strains (Epidermophyton floccosum, Microsporum canis, M . gypseum and Trichophyton mentagrophytes) and pathogenic yeasts (Candida albicans, C . guillermondii, C . krusei, C . tropicalis and Torulopsis glabrata) has been tested following a modification of Aubert's technique . Among the algae species studied, Falkenbergia rufolanosa is the most active in front of all the fungi tested.

Farmaco {Sci}, 1986 Jan, 41(1), 59 - 68
{Benzylidene-5 pyrrolones, furanones and thiophenones . 2 . Quantitative structure-activity relationship}; Galdino SL et al.; Quantitative structure-activity relationships (QSAR) have been derived for twenty two 5-benzylidene furanones, pyrrolones and thiophenones having antifungal activity against Candida albicans . The correlation with the parabolic (Hansch) or bilinear (McFarland-Kubinyi) models are superior to those with the linear models (Free-Wilson or Fujita-Ban), while no significant differences exist between the parabolic and bilinear models . Lipophilicity was necessary for good in vitro activity of these compounds.

Arzneimittelforschung, 1986, 36(1), 20 - 4
Chemical and pharmacological studies of 2-(amino-methyl)acrylophenones; Lesieur I et al.; The structure-activity relationships of nine products of the acrylophenone family have been studied . In a previous report 2-(4-methyl-1-piperazinylmethyl)acrylophenone was shown to be an antimicrotubular drug . The effects of these drugs on the bovine brain tubulin polymerization were determined by a turbidimetric assay . The median inhibitory concentrations (ID50) ranged from 1.5 X 10(-5) to 5 X 10(-5) mol/l . Their action on the inhibition of 3H-colchicine binding to tubulin was determined by DEAE (diethylaminoethyl)cellulose filter assay . These compounds are weak inhibitors of colchicine binding . Pharmacological studies of these drugs revealed a strong inhibition of the human ADP-induced platelet aggregation . Moreover, they markedly decreased the serum cholesterol, triglycerides and phospholipids levels of rats after injection of Triton WR 1339 (4-(1,1,3,3-tetramethylbutyl)phenol polymer with formaldehyde and oxirane) . They inhibited Candida albicans, Penicillium notatum and Aspergillus versicolor growth . Thus, these nine compounds possess interesting pharmacological properties which are very likely to be related to the acrylic moiety of the molecules.

Ann Thorac Surg, 1986 Jan, 41(1), 89 - 90
Candida albicans costochondritis in heroin addicts; Gimferrer JM et al.; The dramatic increase in the number of heroin addicts has led to an increase in the number of infective complications seen, especially those due to Pseudomonas aeruginosa and Candida albicans . In this report we describe our current experience in the surgical treatment of Candida albicans costochondritis . The clinical picture, diagnostic techniques, and surgical therapy receive comment, and a brief review of the literature is given.

Ann Biol Clin (Paris), 1986, 44(3), 225 - 32
{Application of a co-electrosyneresis reaction to the diagnosis and serological surveillance of candidiasis in a hospital milieu}; Poulain D et al.; We have previously described a co-immunofiltration reaction which identifies a specific precipitating system (SPCS) in sera from patients presenting systemic candidiasis . The SPCS is characterized by coalescence with an experimental serum directed against the germinative tubes of Candida albicans . The present study concerns our experience of the use of co-immunofiltration in routine hospital practice . Complete observations involving clinical, mycological and serologic data were selected in order to illustrate various possible developmental trends for SPCS during candidiasis . The SPCS usually develops early infections due to the yeast species most frequently implicated in hospital pathologies; an increase in its intensity reflects a developing infection or the start of therapy . The SPCS disappears slowly and gradually when infectious development is favorable, but its sudden disappearance represents an unfavorable prognosis correlated with detection of circulating antigens . Circulating antigens are also seen in severe cases of candidiasis in which the SPCS is not present . Indeed there is a certain complementarity between these two observations.

Clin Ther, 1986, 8(5), 563 - 7
Treatment of vaginal candidiasis in pregnant women; Weisberg M; Pregnancy creates a climate favorable to the growth of Candida albicans, and this yeast often is difficult to eradicate in pregnant women . Miconazole nitrate administered intravaginally has been found to achieve comparable therapeutic and mycological cure rates in both pregnant and nonpregnant women . A number of clinical studies, using rigid definitions of cure, have demonstrated that miconazole nitrate is significantly better than nystatin, clotrimazole, and butoconazole, a new imidazole derivative, in treating vaginal candidiasis during gestation.

Cancer Invest, 1986, 4(3), 207 - 16
In vivo and in vitro observation of cellular immune parameters in squamous cell carcinoma of the oral cavity and its correlation with tumor load and prognosis; Das SN et al.; In vivo and in vitro observations of cellular immune response in 70 patients with squamous cell cancer of the oral cavity and in 40 age-matched normal controls, were made using delayed hypersensitivity responses to DNCB, PPD, and Candida albicans extract (Dermatophytin 'O'), absolute lymphocyte counts, absolute T-cell numbers, and PHA-induced lymphocyte blastogenesis reactions as parameters . The results were correlated with clinical stage, tumor size, lymph node involvement, tumor differentiation, lymphoreticular responses, and outcome during a one-year follow-up period . A significant degree of impairment of both in vivo and in vitro parameters was found in oral cancer patients compared to normal control . The impairment was more prominent in advanced stages . Lymph node involvement was associated with impaired dermal hypersensitivity to recall antigens as well as a reduced T-cell population and blastogenic response . Only delayed hypersensitivity response to DNCB, PPD, and Candida showed a correlation with histologic features such as tumor differentiation and lymphoreticular response . Although absolute lymphocyte counts and T-cell population were reduced in the primary stage of the disease, the functional capacity of isolated lymphocytes to undergo blast formation was retained . PHA-induced lymphocyte blastogenesis showed a significant impairment only when the tumor was well established and disseminated beyond its local confines . Delayed hypersensitivity responses to DNCB, higher T-cell counts, and blastogenic indices were associated with recurrence-free survival . Immunologic parameters provide prognostic information beyond the clinical stage of the disease . Therefore, it seems that a multiparametric in vivo and in vitro observation of cellular immune response may be useful as an indicator of clinical course and prognosis of patients with squamous cell cancer of the oral cavity.

J Int Med Res, 1986, 14(6), 306 - 10
Effect of fenticonazole in vaginal candidiasis: a double-blind clinical trial versus clotrimazole; Brewster E et al.; Fenticonazole is an imidazole derivative which possesses a broad spectrum antimycotic activity, including activity against Candida albicans . Its therapeutic activity and tolerability have been evaluated, in a double-blind clinical trial versus clotrimazole, in 54 patients affected by mycologically confirmed symptomatic vaginal candidiasis . Both drugs were administered intravaginally as a cream once a day for 7 days . Assessment was by laboratory mycological investigations and symptomatic evaluation . Patients 'cured' at the end of the trial were re-evaluated after 4-6 weeks for possible relapses . Both treatments resulted in a progressive, statistically significant reduction in vaginal symptoms (itching and discharge) and in elimination of Candida in more than 95% of patients . When 'cured' patients were reassessed 4-6 weeks after therapy, relapses occurred in four patients after fenticonazole treatment, but in none following clotrimazole treatment . This apparent difference between treatments is far from being statistically significant and, therefore, may have been a chance occurrence . It should also be noted that patients from the fenticonazole group had a previous history of significantly more frequent episodes of candidiasis suggesting that they may have been at greater risk of re-infection than patients from the control group . The tolerance of both treatments was excellent since no local or systemic signs or symptoms of toxicity were reported . An equally high efficacy and safety for both drugs in the elimination of symptoms and objective evidence of vaginal candidiasis is indicated.

Arch Oral Biol, 1986, 31(9), 617 - 21
Effect on experimental palatal candidosis in the Wistar rat of removal and re-insertion of acrylic appliances; Shakir BS et al.; Palatal candidosis was produced by inoculating Candida albicans 3091 (serotype A) under an acrylic appliance . Two weeks was allowed for infection to occur . Removal of the appliance for a further period of 2 weeks resulted in complete resolution of the lesion histologically but Candida organisms could still be recovered from the mucosal surface . Re-fitting these appliances at the end of this recovery period, without subsequent inoculation, produced a recrudescence of palatal candidosis after a further 2 weeks . One possible explanation is that C . albicans was encouraged to change from the commensal to the pathogenic form in the presence of the palatal appliance.

Rev Pneumol Clin, 1986, 42(4), 183 - 6
{Diagnosis of respiratory allergies to fungi and Candida albicans}; Rancourt MF et al.; Allergy to fungi and Candida albicans raises diagnostic and therapeutic problems that are common to pneumology and allergology . The results of this study seem to support the use of bronchial challenge tests for diagnosis and of specific desensitization for treatment.

Microbios, 1986, 47(191), 97 - 105
Cytological interrelationships between the cell cycle and duplication cycle of Candida albicans; Gow NA et al.; The cytology of nuclear division and septation in the yeast and hyphal phases of Candida albicans growing at 37 degrees C has been studied by fluorescence microscopy after staining of specimens with 4'6-diaminido-2-phenylindole (DAPI) and Calcofluor . Yeast and hyphal cells replicated their nuclei at about 18 min after the emergence of a bud or germ-tube . The site of nuclear division coincided with the future location of the septum in both forms . This occurred at the junction of the bud and parent yeast cell or 6.0 micron from the parent yeast in germ tubes which were formed in medium containing serum . The filamentous forms of a range of clinical and laboratory strains grown in a variety of germ tube-inducing media were all extensively vacuolated . Germ tube extension in all of these media was linear . It is suggested that there is little biosynthesis of cytoplasm during the initial stages of germ tube growth in this organism and that this accounts for the development of the large vacuoles and the linear growth kinetics.

Arch Otorhinolaryngol, 1986, 243(3), 194 - 6
The mycotic flora of adenoids and antibodies to Candida albicans in children; Nuutinen J et al.; We cultured the adenoid tissues of 72 children with recurrent respiratory infections for fungal organisms . We also took fungal cultures of nasopharyngeal secretions from 20 healthy children and 13 healthy adults as controls . Culture for fungi were positive in 15% of the patients, in 15% of the healthy adults and in 25% of the healthy children . Candida albicans, C . parapsilosis, C . tropicalis and Aspergillus sp . were the most common organisms found . In studying the children with recurrent respiratory infections, we were unable to find any significant correlation between the positive cultures and the age, type of day-care and previous antibiotic therapy given . We then studied the hemagglutination titers against C . albicans in 44 patients . This titer was 1:160 or lower in all but three patients, and was 1:320 in these latter three patients . However, fungal cultures were negative in all patients having hemagglutination titers of 1:80 or more.

Drugs Exp Clin Res, 1986, 12(6-7), 635 - 43
Cell wall of pathogenic yeasts and implications for antimycotic therapy; Cassone A; Yeast cell wall is a complex, multilayered structure where amorphous, granular and fibrillar components interact with each other to confer both the specific cell shape and osmotic protection against lysis . Thus it is widely recognized that as is the case with bacteria, yeast cell wall is a major potential target for selective chemotherapeutic drugs . Despite intensive research, very few such drugs have been discovered and none has found substantial application in human diseases to date . Among the different cell wall components, beta-glucan and chitin are the fibrillar materials playing a fundamental role in the overall rigidity and resistance of the wall . Inhibition of the metabolism of these polymers, therefore, should promptly lead to lysis . This indeed occurs and aculeacin, echinocandin and polyoxins are examples of agents producing such an action . Particular attention should be focused on chitin synthesis . Although quantitatively a minor cell wall component, chitin is important in the mechanism of dimorphic transition, especially in Candida albicans, a major human opportunistic pathogen . This transition is associated with increased invasiveness and general virulence of the fungus . Yeast cell wall may also limit the effect of antifungals which owe their action to disturbance of the cytoplasmic membrane or of cell metabolism . Indeed, the cell wall may hinder access to the cell interior both under growing conditions and, particularly, during cell ageing in the stationary phase, when important structural changes occur in the cell wall due to unbalanced wall growth (phenotypic drug resistance).

Drugs Exp Clin Res, 1986, 12(6-7), 585 - 94
Drug delivery systems: optimising the structure of peptide carriers for synthetic antimicrobial drugs; Payne JW; This paper discusses the concept of smugglins, i.e., molecules that are formed by attaching to, or incorporating into, normal cell nutrients varied moieties as a means of transporting otherwise impermeant substances into cells . Examples of antimicrobial smugglins that use this principle in Nature are described . The rationally designed antibiotic smugglins investigated to date are critically reviewed . Criteria for the design of optimal peptide carriers for antimicrobial smugglins are considered . A computer-linked, continuous-flow system for rapid measurement of the kinetic parameters for substrate transport via peptide permeases is described which, together with current molecular, genetic and biochemical techniques, now provides the means to obtain the information on which rational design should be based; examples are given for Escherichia coli and Candida albicans . After an uncertain commercial start, it now seems likely that increasing understanding of the uptake processes and other relevant features will make drug targeting using peptide carriers an achievable goal . Certainly their widespread occurrence in Nature should provide added incentive for the design of synthetic smugglins.

Drugs Exp Clin Res, 1986, 12(6-7), 577 - 83
Anticapsin: an active site directed inhibitor of glucosamine-6-phosphate synthetase from Candida albicans; Milewski S et al.; L-beta-(2,3-epoxycyclohexanono-4)-alanine, an active fragment of the antibiotic tetaine, identical to the antimetabolite anticapsin, is a powerful inhibitor of partially purified glucosamine-6-phosphate synthetase (2-amino-2-deoxy-D-glucose-6-phosphate ketol isomerase, aminotransferring, EC 5.3.1.19) from pathogenic fungus Candida albicans . Anticapsin was demonstrated to be a competitive inhibitor of this enzyme with respect to L-glutamine and uncompetitive with respect to D-fructose-6-phosphate . Incubation of anticapsin with glucosamine-6-phosphate synthetase in the absence of glutamine led to the formation of an inactive enzyme, irreversibly modified . The inactivation obeyed saturation kinetics; the determined Kinact was 9.5 X 10(-6) M . Addition of glutamine protected the enzyme against inactivation by anticapsin . Reaction of anticapsin with the enzyme exhibited characteristics of affinity labelling of the glutamine binding site . Probably the inactivation proceeds via an alkylation of cysteine residue at the glutamine binding site.

Circ Shock, 1986, 19(3), 275 - 82
Microbial filtrates activate granulocytes without complement or prostaglandins; Yellin SA et al.; Cardiorespiratory dysfunction in sepsis may be mediated by circulating complement, activated leukocytes, prostaglandins, or by a direct effect of endotoxin . The purposes of this study were to determine if pathogenic microbes produce these substances and to evaluate the direct effects of substances released by micro-organisms on granulocyte aggregation (GA) . Escherichia coli, (E . coli), Aeromonas hydrophila (Aeromonas h.), Staphylococcus aureus (S . aureus), and Candida albicans, (Candida a.) were incubated in broth to a concentration of 10(9)/ml . Broth was filtered and analyzed by radioimmunoassay for complement components C3a and C5a, thromboxane B2 (TxB), and prostaglandin 6-keto-F1 alpha (PGI) and by the limulus amebocyte lysate test (LAL) for endotoxin . GA, % of maximum zymosan activated aggregation (% max . T), was performed with broth, microbial filtrates, and endotoxin or normal purified human leukocytes in HBSS . Organisms were incubated in broth (B), broth + 0.0135 mg/ml arachidonic acid (BA), and broth + arachidonic acid + indomethacin (BAI) . Broth alone was the control (C) . Results: C3a, C5a, TxB, and PGI were not detectable in C broth or in any microbian filtrate . LAL was positive in all filtrates, but negative in C broth . GA responses were significantly greater in E . coli (56 +/- 5% max T) and Aeromonas h . (57% +/- 8% max T) compared to S . aureus (10 +/- 5% max T), Candida a . (14 +/- 8% max T) and C broth (1 +/- 1% max T) . GA with purified E . coli endotoxin at concentrations measured in the filtrates was not related to the GA responses the original filtrates.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrob Agents Chemother, 1986 Jan, 29(1), 33 - 9
Hydrophobic polyoxins are resistant to intracellular degradation in Candida albicans; Smith HA et al.; Two novel polyoxins, N-epsilon-(octanoyl)-lysyl-uracil polyoxin C (Oct-Lys-UPOC) and N-gamma-(octyl)-glutaminyluracil polyoxin C (Oct-Gln-UPOC), were synthesized by reacting uracil polyoxin C with the appropriate amino acid p-nitrophenyl ester . Oct-Lys-UPOC and Oct-Gln-UPOC were strong inhibitors (Kis = 1.7 X 10(-6)M) of chitin synthetase from Candida albicans membrane preparations . In a permeabilized-cell assay, Oct-Gln-UPOC had a 10-fold-lower inhibitory activity toward chitin synthetase than did the Oct-Lys-UPOC analog . Both compounds were resistant to hydrolysis by a cell extract of C . albicans H317; however, Oct-Gln-UPOC was hydrolyzed with a half-life of 23 min by a permeabilized-cell preparation . Oct-Lys-UPOC was resistant to hydrolysis by permeabilized cells . Oct-Gln-UPOC and Oct-Lys-UPOC did not compete with the transport of peptides or uridine into the cell . At concentrations up to 2 mM these two new polyoxins were ineffective in the inhibition of cell growth or reduction of cell viability, but they induced aberrant morphologies in C . albicans at a concentration of 0.25 mM . These data suggest that polyoxins containing hydrophobic amino acids retain strong chitin synthetase inhibitory activity and are resistant to cellular hydrolysis . They provide the first example of effective synthetic chitin synthetase inhibitors which are stable inside C . albicans.

Pharmatherapeutica, 1986, 4(8), 525 - 31
Comparison of terconazole and clotrimazole vaginal tablets in the treatment of vulvovaginal candidosis; Kjaeldgaard A; The clinical efficacy of terconazole (triaconazole), a new triazole ketal structurally similar to ketoconazole, was evaluated in a single-blind, randomized comparative clinical trial including 60 patients with symptoms and clinical signs of vulvovaginal candidosis confirmed by microscopic examination and positive culture for Candida albicans . Three comparable groups were treated with 200 mg clotrimazole or 80 mg terconazole vaginal tablets once daily for 3 consecutive days, or one 240 mg terconazole vaginal tablet followed by 2 identical placebo pessaries . No differences in relief and initial symptomatic cure according to patient recordings on diary cards were demonstrated between the three regimens . Cure rates were 90% or more in all treatment groups 1 week after completion of therapy . At the second follow-up visit 3 weeks later, a significantly higher mycological cure rate (94%), due to significantly better therapeutic response in patients with recurrent vulvovaginal candidosis, was recorded after 3-day therapy with terconazole, while the mycological cure rates after clotrimazole and single-dose terconazole treatment only were 65% and 55%, respectively . It was concluded that terconazole represents an efficient and well-tolerated therapeutic alternative in the topical treatment of vulvovaginal candidosis.

J Gen Microbiol, 1986 Jan, 132 ( Pt 1), 15 - 9
A Candida albicans mutant impaired in the utilization of N-acetylglucosamine; Corner BE et al.; Indicator plates containing eosin, methylene blue, glucosamine and proline were used to select mutants of Candida albicans impaired in the utilization of glucosamine . One such mutant, strain hOG298, grew on glucosamine at a slower rate than the parent and was severely impaired in growth on N-acetylglucosamine . The mutant was unable to express the first three steps in the N-acetylglucosamine pathway: viz the permease, N-acetylglucosamine kinase and N-acetylglucosamine-6-phosphate deacetylase . Glucosamine-6-phosphate deaminase was, however, induced by N-acetylglucosamine . The mutant still possessed a constitutive uptake system and kinase activity for glucosamine but glucosamine neither increased the glucosamine kinase activity nor induced N-acetylglucosamine kinase . These findings accounted for the decreased growth rate on glucosamine . The parent strain formed germ-tubes in N-acetylglucosamine or 4% (v/v) serum but the mutant formed germ-tubes only in serum.

Curr Med Res Opin, 1986, 10(2), 82 - 8
Hexetidine ('Oraldene'): a report on its antibacterial and antifungal properties on the oral flora in healthy subjects; Wile DB et al.; A randomized, double-blind crossover trial, in 10 adult healthy subjects, was carried out to compare the antibacterial and antifungal activity of a 0.1% solution of hexetidine with that of placebo . The pre-dosing oral flora of the subjects was assessed from saliva samples cultured for aerobic and anaerobic bacteria, as well as Candida albicans . Subjects then rinsed their mouths for 1 minute 3-times a day with 15 ml 0.1% hexetidine or placebo, saliva samples being collected at 2 minutes, 30 minutes, 1 hour, 3 hours and 5 hours post-dosing . Dosing was continued for 8 consecutive days on each treatment with an intervening wash-out period of 1 week . Hexetidine reduced aerobic bacterial counts on Day 1 and Day 8 by a maximum of 83% and 86%, respectively, at 2 minutes post-dosing . The reductions were statistically significantly lower than placebo up to 1 hour post-dose on Day 1 and up to 3 hours post-dose on Day 8 . Similarly for anaerobic bacterial counts, 92% and 88% maximum reductions were recorded on Day 1 and Day 8, which again were significantly lower than placebo for up to 3 hours post-dose . For Candida albicans, however, the maximum reduction was 91% on the first day and 67% on Day 8, maintained for 30 minutes post-dosing . Although not eradicating completely aerobic and anaerobic bacteria, it is concluded that the substantial reduction in their numbers should prove clinically useful.

J Infect, 1986 Jan, 12(1), 79 - 83
Analysis of the antibody response developing in an infant with Candida albicans meningitis; Burnie JP et al.; A case of meningitis due to Candida albicans in a neonate is described . This is the first report of an immunoblot analysis of both serial samples of serum and cerebrospinal fluid in relation to C . albicans antigens . The western blot technique demonstrated that the mother had IgM antibody against five candidal antigens, including one of molecular weight 47 kDaltons, but only a small amount of IgG antibody against two antigens of molecular weight 104 kDaltons and 60 kDaltons respectively . The baby produced IgM antibody and then IgG antibody against an antigen of 47 kDaltons molecular weight, and this was associated with recovery.

J Cardiovasc Surg (Torino), 1986 Jan-Feb, 27(1), 72 - 8
Candida immunity in patients undergoing surgical treatment for heart valve disease; Ryhanen P et al.; The appearance of Candida antigen (Latex agglutination method), Candida antibodies (indirect immunofluorescence) and positive fungal cultures as well as the lymphocyte transformation response to Candida antigen "in vitro" was studied in a series of 37 successive patients before and after heart valve replacement . The Candida antigen test was positive preoperatively in 11/36 (31%) and postoperatively in 14/36 (39%) of the patients and in 2/200 (1%) of the controls (blood donors) . The differences in the frequencies of positive tests between the patient group and the control group are significant (p less than 0.001) . The lymphocyte response to Oidiomycin (Candida albicans) preoperatively was greater than the mean control value in 6/11 (54.5%) of the patients showing a positive Candida antigen test, but only in 4/25 (16.0%) of the patients who were Candida antigen negative . The total number of lymphocytes and the number of ANAE positive (T) cells as well as the lymphocyte response to Oidiomycin (OID), tuberculoprotein (PPD) and phytohaemagglutinin (PHA) decreased markedly postoperatively . Candida antibody titres were positive (greater than or equal to 1:128) in 3/37 (8%) of the postoperative patients and in 2/84 (2.4%) of the controls . This difference is not significant . Positive Candida antibody titres were found postoperatively in 15/37 (41%) of the patients, which is a significantly higher frequency than that seen preoperatively (p less than 0.005) . More positive fungal cultures from throat specimens (p less than 0.005) were found in the patient group before surgery than in the control group (hospital personnel) . After surgery the number of positive fungal cultures in these cases decreased (p less than 0.001) due to the use of oral antifungal prophylaxis with nystatin tablets.(ABSTRACT TRUNCATED AT 250 WORDS)

Exp Hematol, 1986 Jan, 14(1), 60 - 5
Effect of 1,25 dihydroxyvitamin D3 and retinoic acid on normal human pluripotent (CFU-mix), erythroid (BFU-E), and myeloid (CFU-C) progenitor cell growth and differentiation patterns; Nagler A et al.; The modulatory effect of 1,25 dihydroxyvitamin D3 (vit D) and 13 cis retinoic acid (retinoic acid) on the growth and differentiation of normal human pluripotent stem cell, erythroid, and myeloid progenitor cell growth was studied using semisolid methylcellulose clonal assay . Dose response curves showed that maximal increments of myeloid colony (CFU-C) growth (150%) occurred with vit D at 2 X 10(-9) -2 X 10(-8) M and with retinoic acid (184%) at 1 X 10(-7) M . Vit D caused a 134% increase in macrophage colonies (CFU-M) and a decrease in granulocytic (CFU-G) and granulocyte-macrophage colonies (CFU-GM) (50% and 58%, respectively, as compared to the control) . Retinoic acid did not alter the differentiation pattern of myeloid colonies (CFU-M, CFU-G, and CFU-GM) . Vit D at 2 X 10(-8) M had an inhibitory effect on BFU-E (62% growth of control) and did not affect CFU-mix growth . Retinoic acid at 10(-7) M did not alter the growth of either BFU-E or of CFU-mix . Cellular differentiation studies in liquid suspension showed that vit D caused a 213% increase in monocyte-macrophages and a 56% and 26% decrease in immature and mature granulocytes, respectively . Retinoic acid caused a marked (79%) decrease in immature granulocytes whereas the percentage of mature granulocytes and monocyte-macrophages was not changed . Assessment of phagocytosis and killing of Candida albicans (C.A.) by cultured monocyte-macrophages and granulocytes exposed to vit D and retinoic acid demonstrated that treated cells had the same capability to phagocytose and kill C.A . as did untreated cells.

Diagn Microbiol Infect Dis, 1986 Jan, 4(1), 83 - 6
Irrelevance of growth phase with respect to the Bay n 7133 and ICI 153,066 susceptibilities of Candida albicans; Beggs WH et al.; Miconazole at 10(-5)-10(-4) M can kill Candida albicans in the logarithmic phase, but ketoconazole, the only established oral antifungal azole, cannot . Lethal potential in relation to growth phase was studied with Bay n 7133 and ICI 153,066, two recently developed oral triazoles . Each was strictly fungistatic regardless of phase of growth and was almost identical in effect to ketoconazole.

Am J Med, 1986 Jan, 80(1), 116 - 8
Tricuspid valve Candida endocarditis . Successful treatment with valve-sparing debridement and antifungal chemotherapy in a multiorgan transplant recipient; Pruett TL et al.; Tricuspid valve Candida albicans endocarditis developed in a multiple-organ transplant recipient six months after successful treatment of Candida peritonitis . She has had no recurrence or valvular incompetence two years after valve-sparing debridement of the vegetation and prolonged therapy with amphotericin B . This is the second report of long-term success following valve-sparing debridement for tricuspid valve Candida endocarditis . In selected patients without annular involvement or gross valve destruction, excision of the fungal vegetation may allow for long-term cure and a competent valve.

J Urol, 1986 Jan, 135(1), 22 - 5
Failure of immunotherapy for metastatic renal cell carcinoma; Fowler JE Jr; Prompted by reports of tumor regression among patients with metastatic renal cell carcinoma treated by injection of an aggregated autologous or allogeneic tumor antigen with a nonspecific adjuvant, we studied the efficacy of this therapy in 23 patients . Following nephrectomy or excision of a metastatic lesion 16 patients were treated with an aggregated autologous tumor antigen combined with Candida albicans antigen . There were only 2 minimal responses . Seven patients judged unsuitable for an operation were treated with an aggregated allogeneic antigen . There were no objective responses . We conclude that these treatment regimens have minimal activity against metastatic renal cell carcinoma.

J Bacteriol, 1986 Jan, 165(1), 61 - 5
Isolation and morphological characterization of a mycelial mutant of Candida albicans; Hubbard MJ et al.; In this paper we describe the isolation of a novel strain of Candida albicans which is a mycelium at ambient temperatures . Mutagenesis of C . albicans ATCC 10261 with N-methyl-N-nitro-N-nitrosoguanidine followed by plating on solid media at 28 degrees C yielded colony morphology variants which were characterized by a raised, rough-surfaced colony of irregular outline in marked contrast to the flat, shiny circular colonies of the parental 10261 strain . One mutant colony, hOG301, was studied in detail . Strain hOG301 was stable and exhibited mycelial morphology over a wide temperature range (5 to 40 degrees C) in several media . The hyphae comprising hOG301 mycelium were examined by light microscopy, scanning electron microscopy, and transmission electron microscopy and showed morphological features described in the literature as being typical of both true hyphae and pseudohyphae . In contrast to 10261, hOG301 was not pathogenic after intraperitoneal injection in mice . This is the first report of a mycelial C . albicans that is stable at ambient temperatures.

Infect Immun, 1986 Jan, 51(1), 337 - 43
Variability in expression of cell surface antigens of Candida albicans during morphogenesis; Brawner DL et al.; The location and expression of two different cell surface antigens on germinating and nongerminating Candida albicans cells was examined by using transmission electron microscopy after labeling with monoclonal antibodies (H9 or C6) and immunocolloidal gold . Immunodeterminant expression of the two carbohydrate antigens was followed from early germination events through 20 h of development . The determinant detected by H9 antibody, which was initially lost from the mother cell surface and preferentially expressed only on hyphae during the first 4 h of germination, reappeared on the mother cell by 20 h, whereas the antigen detected by antibody C6 was continually expressed on mother cells and germ tubes throughout germination.

Infect Immun, 1986 Jan, 51(1), 327 - 36
Ultrastructural and biochemical studies of two dynamically expressed cell surface determinants on Candida albicans; Brawner DL et al.; Variability in the expression of two different cell surface carbohydrate determinants was examined with two agglutinating immunoglobulin M monoclonal antibodies (H9 and C6) and immunoelectron microscopy during growth of three strains of Candida albicans . A single strain of Candida parapsilosis did not express either antigen at any time during growth . Antigens were detected on the surface of C . albicans by agglutination tests with either H9 or C6 over a 48-h growth period . The difference in specificities of the monoclonal antibodies was demonstrated by Ouchterlony double-diffusion tests with solubilized antigens and by variabilities in the reactivity of the agglutinins among yeast strains . The antigenic determinants were isolated by specific immunoprecipitation and protease digestion and characterized by methods including high-pressure liquid chromatography, gas-liquid chromatography, and mass spectroscopy with both chemical and electron ionization . These determinants both contain mannose and glucose . In the case of antigen H9, an additional carbohydrate was detected with gas chromatography and mass spectroscopy . The location of antigens on individual cells was determined by indirect labeling of the determinants, first reacting cells with H9 or C6 followed by goat anti-mouse antibody conjugated with 20-nm colloidal gold particles . Transmission electron microscopy was used to examine cells . The antigens that were reactive with the monoclonal antibodies were associated with a flocculent surface layer . Expression of this layer and expression of the antigens is a dynamic process which is growth phase and strain dependent . The antigens were not expressed on very young cells and disappeared from the cell surface of most C . albicans strains with age . The use of monoclonal antibody to cell surface determinants may allow characterization of cell surface antigens of C . albicans and be helpful in establishing receptors which mediate adherence.

Infect Immun, 1986 Jan, 51(1), 307 - 13
Rapid killing of monocytes in vitro by Candida albicans yeast cells; Danley DL et al.; To study the interaction between Candida albicans blastoconidia and human phagocytes, we incubated peripheral leukocytes with fungi for 1 h at 37 degrees C and stained the cells with fluorescent vital stains ethidium bromide (EB) and fluorescein diacetate . Fungi that had been phagocytosed showed little staining; however, some leukocytes containing blastoconidia exhibited nuclear staining with EB, even though their cell membranes showed no signs of penetration by fungi . The number of EB-positive leukocytes was related to viability of the yeast cells and the temperature at which they were maintained before use . Because efforts to quantitate EB-positive leukocytes microscopically were frustrated by cell aggregation, we labeled the leukocytes with 51Cr and measured isotope release . We determined that leukocytes incubated with viable fungi released significantly more isotope than cells incubated alone or with killed blastoconidia . Furthermore, 51Cr release correlated directly with concentration of fungi in the assay, time of incubation, and temperature at which fungi were maintained before use . Using a number of isolates of C . albicans and several other species of Candida, we found that all exhibited cytotoxic activity against leukocytes, but the level of activity varied among organisms . Finally, we depleted or enriched peripheral leukocytes for specific cell populations and determined that only monocytes released more 51Cr after incubation with viable blastoconidia . Blastoconidia can lyse phagocytic cells through germination and penetration of cell membranes within 1 to 2 h, but the cytotoxic phenomenon we describe occurs within 15 to 30 min after yeast cells have been phagocytosed . Therefore, this capacity may represent a more immediate response by blastoconidia against phagocytosis and killing by monocytes.

Infect Immun, 1986 Jan, 51(1), 157 - 62
Abilities of human oligodendroglial cells and mouse Schwann cells to phagocytose Mycobacterium leprae and other mycobacteria; Saito H et al.; Human oligodendroglial KG-1-C cells derived from human cerebral mixed glioma and mouse Schwann cells derived from dorsal root ganglion were studied with respect to their abilities to phagocytose various mycobacteria, especially Mycobacterium leprae, and other microorganisms . KG-1-C cells phagocytosed M . leprae at a markedly higher rate than BALB/3T3, BHK 21, HeLa S3, mKS-A TU-7, XC, TSV-5, N-18, and Schwann cells but at a lower rate than peritoneal macrophages . Schwann cells also exhibited substantial phagocytic ability against M . leprae, and their phagocytic rate against M . leprae was much higher than that of N-18 cells, derived from neurons . KG-1-C and Schwann cells phagocytosed mycobacteria other than M . leprae, and their phagocytic patterns with various mycobacteria were similar, thereby suggesting that their abilities to phagocytose mycobacteria were based on the same cellular mechanism . The time course of phagocytosis of M . leprae by KG-1-C cells markedly differed from that by macrophages, indicating differences in the cellular mechanisms of M . leprae phagocytosis . KG-1-C cells also ingested microorganisms other than acid-fast bacilli, such as Staphylococcus aureus, Listeria monocytogenes, Bacillus subtilis, and Escherichia coli but not Candida albicans . They also phagocytosed latex beads (0.8-micron diameter) but not sheep erythrocytes . Microscopically, most mycobacterial cells were ingested in the perikaryon of KG-1-C cells and Schwann cells.

Infect Immun, 1986 Jan, 51(1), 102 - 9
Characterization of cerulenin-resistant mutants of Candida albicans; Hoberg KA et al.; Cerulenin, an inhibitor of fatty acid biosynthesis, has been used to study the role of the plasma membrane in germination of Candida albicans . To further elucidate this association, spontaneous, cerulenin-resistant mutants of C . albicans were isolated . Two of the mutants, 4918-2 and 4918-10, were compared biochemically with wild-type cells (4918) . All strains grew equally well at 37 degrees C and synthesized fatty acids at comparable rates in the absence of the drug . In the presence of cerulenin, wild-type cells did not proceed through a logarithmic growth stage and exhibited a significantly impaired ability to incorporate {3H}acetate into newly synthesized lipid material . All strains were examined ultrastructurally . Alterations were observed in the membranous structures of cerulenin-treated wild-type cells . Such changes were not observed in cerulenin-treated mutant strains . Further examination of mutant strains revealed differences in cell wall protein and polysaccharide compositions when compared with those of wild-type cells . These apparent alterations in cell surface components may be correlated with the reduced abilities of mutant strains to adhere, in vitro, to mammalian cells.

Drugs, 1986 Jan, 31(1), 29 - 51
Tioconazole . A review of its antimicrobial activity and therapeutic use in superficial mycoses; Clissold SP et al.; Tioconazole is a substituted imidazole antimicrobial agent structurally related to other drugs in this group . It has been shown to have a broad spectrum of activity in vitro against dermatophytes and yeasts, as well as against some chlamydia, trichomonads and Gram-positive bacteria . Both open and controlled clinical trials have clearly demonstrated the efficacy and safety of topical preparations of tioconazole for treating superficial dermatophyte or yeast infections of the skin and vaginal candidiasis . In comparative studies it was at least as effective as alternative imidazole antifungal drugs, and in a few trials significantly greater efficacy has been reported for tioconazole, compared with clotrimazole, miconazole, econazole and systemic ketoconazole . Preliminary studies in other clinical areas suggest tioconazole may be useful for treating onychomycosis (in a special nail formulation), napkin-rash due to Candida albicans, impetigo, and vaginal trichomoniasis, although comparative studies are needed in each of these settings to clearly assess its relative place in therapy . Thus, tioconazole is an effective and well tolerated treatment for vaginal candidiasis and superficial fungal infections of the skin.

Acta Derm Venereol Suppl (Stockh), 1986, 121, 51 - 5
Yeast organisms associated with human oral leukoplakia; Krogh P et al.; Oral leukoplakia is a lesion of variable clinical behaviour and a malignant transformation rate of 3-6% . Leukoplakia exhibits various histologic features, hyperkeratinization being the most consistent . As yeast organisms have been encountered in a high proportion of leukoplakia cases, a causal role has been suggested for these organisms . Candida albicans is by far the most commonly isolated yeast from leukoplakia, but also other Candida species as well as Torulopsis and Saccharomyces species may be encountered . The species composition of the mycoflora in leukoplakia does however not differ from that of normal oral mucosa . Subspecies differentiation of C . albicans has revealed the existence of different oral strains between individuals and further, strain differences of C . albicans in leukoplakia and in normal mucosa have been observed . This procedure may lead to isolation and identification of the yeast organisms causally associated with leukoplakia.

J Clin Immunol, 1986 Jan, 6(1), 9 - 20
Functional heterogeneity of human antigen-presenting cells: presentation of soluble antigen but not self-Ia by monocytes; Moreno J et al.; These studies were undertaken to examine the phenotype of the antigen-presenting cells (APC) circulating in human peripheral blood . Cells adherent to glass were found to be efficient APC, restoring antigen-induced 3H-thymidine incorporation to T4-positive T cells that had been rigorously depleted of contaminating APC . In order to identify the APC within the glass-adherent cells (AC), these cells were stained with a number of monocyte-specific monoclonal antibodies (Mo-Mab) including 3C10, 63D3, and 61D3, and the Mo-Mab-positive and -negative cells were separated with the fluorescence-activated cell sorter . This method of preparation yielded Mo-Mab(+) AC populations that were more than 98% positive for the relevant Mab when reanalyzed with the fluorescence-activated cell sorter . Less than 1% of the Mo-Mab(-) AC populations were positive when reanalyzed with the Mab used for the separation . However, each Mo-Mab(-) AC population was contaminated with variable numbers (4-60%) of Mo as detected by morphologic criteria, histochemical analysis for esterase activity, or staining with a different Mo-Mab . Both Mo-Mab(+) and (-) AC populations were found to be similarly effective APC, with as few as 500 cells/well supporting responses to streptokinase-streptodornase, tetanus toxoid, and Candida albicans antigen . In the absence of antigen, only 3C10(-), 63D3(-), or 61D3(-) AC consistently stimulated 3H-thymidine incorporation of autologous T4 cells; large numbers (greater than 5 X 10(3)/well) of APC were necessary to induce this response . These results support the conclusion that cells identified by Mo-specific Mab are capable of functioning as APC, inducing 3H-thymidine incorporation in response to exogenous antigens . However, Mo-Mab(+) AC are not unique in this activity since Mo-Mab(-) AC also appeared to be able to present antigen . These Mo-Mab(-) AC appear to contain the majority of cells inducing autologous T4-cell reactivity.

Curr Genet, 1986, 10(9), 685 - 93
Segregant-defective heterokaryons of Candida albicans; Sarachek A et al.; Heterokaryons (hets) of the asexual, pathogenic yeast Candida albicans obtained by fusing protoplasts of complementing auxotrophic strains generate large numbers of parental-type auxotrophic monokaryons by random assortment of single nuclei into blastospores, and smaller numbers of monokaryons bearing hybrid nuclei formed through either karyogamy or the transfer of genetic material from one het nucleus to another . Het populations grown at 30 degrees C or 37 degrees C contain high frequencies (approx . 5%-10%) of two kinds of stable variants peculiar specifically for segregation of parental-type monokaryons: NS variants produce inviable auxotrophic monokaryons of one or both parental classes while AT variants yield parental-type monokaryons which grow very slowly . Variant frequencies are not affected by the wild-type strain background of hets, or the auxotrophies used to force heterokaryosis . However, both kinds of variants are induced by growth at 25 degrees C or by treatments with certain chemical or physical metabolic inhibitors . Evidence is presented that variant nuclei of independent origins carry different nutritionally irreparable recessive lethal (NS) or debilitating (AT) defects acquired in the course of actual or potential internuclear transfers of genetic material within het cells . The high incidence of variants, therefore, indicates considerable intrinsic genetic instability among het nuclei . Significances of these observations for parasexual genetic analyses of C . albicans and other yeasts through protoplast fusions are considered.

Ann Fr Anesth Reanim, 1986, 5(6), 620 - 2
{Nosocomial Candida albicans septicemia in parenteral alimentation through a peripheral vein}; Tritschler C et al.; Fungal septicaemias during total parenteral nutrition are frequent, but their occurrence during parenteral nutrition via a peripheral vein is uncommon . A case of disseminated candidemia with ocular and renal localizations during parenteral nutrition via a peripheral vein is reported in a 24 year old patient hospitalized for primary cerebellar haemorrhage . The case history showed the importance of early ophthalmologic examination in all septicaemic cases . The diagnosis was confirmed by nine positive blood cultures and immunological tests, but the dosage of soluble antigens remained negative . The part played by a contaminated perfusion bottle out-of-date was suggested, but could not be proved absolutely . The assessment of the immune state could wrongly suggest an acquired immunodeficiency syndrome, for it has been demonstrated that Candida albicans itself had an immunosuppressive activity.

Acta Haematol, 1986, 75(2), 116 - 9
Unexpected presentation of deep candidiasis in a recipient of a mismatched bone marrow transplant; Bandini G et al.; A Caucasian male of 37 years with acute non-lymphoid leukemia underwent a mismatched allogeneic bone marrow transplantation; he was in relapse but otherwise well . After conditioning with cyclophosphamide, total body irradiation and cytosine arabinoside, he received from his sister a graft depleted of T lymphocytes and cyclosporin A . Soon after transplantation he developed fever and a skin rash, followed, after response to high-dose steroids, by fever, acute renal failure, jaundice, progressive loss of consciousness and death after 2 weeks of transplant . Unexpectedly, autopsy revealed deep candidiasis of the liver and kidneys; here the histologic pattern was peculiar, because tubules were filled and occluded by Candida albicans organisms and hyphae . The uniqueness of this case and the fulminating clinical course did not allow to start an appropriate antifungal therapy.

Microbiol Immunol, 1986, 30(10), 957 - 67
Protective effect of acidic mannan fraction of bakers' yeast on experimental candidiasis in mice; Okawa Y et al.; An acidic fraction of bakers' yeast mannan, WAM025, showed a significant protective effect against Candida albicans infection in mice, but a neutral fraction of the same bakers' yeast mannan, WNM, did not exhibit this effect . Moreover, pretreatment with WAM025 resulted in a marked reduction of proliferation of C . albicans cells in the organs of the infected mice . We investigated the stimulative effect of these mannan fractions on the function of mouse peritoneal phagocytes, and found that mice administered WAM025 showed a greater increase in the number of peritoneal exudate cells, macrophages and polymorphonuclear leucocytes (PMN), than the mice treated with WNM, especially in the proportion of PMN . Peritoneal phagocytes, PMN and macrophages obtained from WAM025-treated mice showed marked candidacidal activity . Of the phagocytes, PMN were responsible for the larger part of the candidacidal activity . The myeloperoxidase activities of PMN and macrophages in WAM025-treated PEC were greater than in untreated macrophages . The myeloperoxidase activity of WAM025-treated PMN was significantly greater than that of WAM025-treated macrophages . This activity paralleled the active oxygen-releasing activity of the phagocytes . On the other hand, the phagocytic activity of phagocytes from mice administered WNM or WAM025 for C . albicans cells was identical to that of untreated phagocytes . WAM025 seems to cause enhance elimination of the pathogen from mice, by increasing the number and candidacidal activity of phagocytic cells.

Mol Cell Biol, 1986 Jan, 6(1), 142 - 9
Integrative transformation of Candida albicans, using a cloned Candida ADE2 gene; Kurtz MB et al.; Candida albicans is a diploid dimorphic yeast with no known sexual cycle . The development of a DNA transformation system would greatly improve the prospects for genetic analyses of this yeast . Plasmids were isolated from a Candida Sau3A partial library which complements the ade2-1 and ade2-5 mutations in Saccharomyces cerevisiae . These plasmids contain a common region, part of which, when subcloned, produces ade2 complementation . Among the small number of auxotrophs previously isolated in C . albicans, red adenine-requiring mutants had been identified by several groups . In two of these strains, the cloned Candida DNA transformed the mutants to ADE+ at frequencies of 0.5 to 5 transformants per micrograms of DNA . In about 50% of the transformants, plasmid DNA sequences became stably integrated into the host genome and, in the several cases analyzed by Southern hybridization, the DNA was integrated at the site of the ADE2 gene in one of the chromosomal homologs.

Eur J Clin Pharmacol, 1986, 30(1), 99 - 104
Augmentation of human blood monocyte microbicidal activity by RU 41740, a glycoprotein extract from Klebsiella pneumoniae; Nielsen H; Non-specific activation of host defences may have a significant impact on the outcome of infections in the immunocompromized patient . RU 41740, a glycoprotein extract from Klebsiella pneumoniae, effective in increasing resistance to experimental infections in animals, has been examined in vitro for its effect on human blood monocyte locomotion, phagocytosis, killing of Candida albicans, and release of superoxide anion . RU 41740 had no chemo-attractant activity nor any effect on monocyte chemotactic and phagocytic function . Candidacidal capacity and superoxide anion production by monocytes were significantly enhanced after preincubation with RU 41740 greater than 1.0 microgram/ml . The effect was dose- and time-dependent and was not influenced by the presence of lymphocytes or their culture supernatants . This suggests a direct interaction with monocytes as the mechanism of action of the extract.

Scand J Infect Dis, 1986, 18(1), 49 - 52
Alterations in the human oropharyngeal microflora related to therapy with aztreonam, moxalactam and ampicillin plus sulbactam; Heimdahl A et al.; 33 patients undergoing colorectal surgery were treated prophylactically with aztreonam (19 patients), moxalactam (10 patients) and ampicillin plus sulbactam (4 patients) . The effect on the normal oropharyngeal microflora and new colonization of oropharynx were studied during and after the treatment . Aztreonam had minor effect on the normal flora but induced colonization with staphylococci . Moxalactam suppressed gram-negative aerobic and anaerobic bacteria and promoted colonization with Candida albicans . Ampicillin plus sulbactam had marked effect on the normal flora and suppressed aerobic as well as anaerobic bacteria . New colonization with enteric gram-negative rods or fungi was observed in all patients.

Dermatol Clin, 1986 Jan, 4(1), 137 - 49
Fungal infections in children; Caputo RV; Fungal infections of the skin represent a relatively common problem in pediatric dermatology . Although fungal infections of the feet, nails, and groin are uncommon in the pediatric age group, fungal infections of the scalp are very common and must be diagnosed early because they may lead to permanent hair loss if left untreated . Perhaps the most significant change in fungal infections in children has occurred in tinea capitis, including the causative agent and the type of infection this organism may produce; these factors are focused upon in this article . Also discussed are infections caused by the yeast organisms Candida albicans and Pityrosporum orbiculare, as well as the deep mycoses, specifically chromoblastomycosis and cutaneous aspergillosis.

J Clin Microbiol, 1986 Jan, 23(1), 46 - 52
Immunoblot analyses of Candida albicans-associated antigens and antibodies in human sera; Manning-Zweerink M et al.; We tested 10 patient sera for the presence of immunoglobulin G (IgG) antibodies to Candida albicans and for C . albicans antigens by immunoblot analysis (i.e., electrotransfer blot radioimmunoassay) (G . E . Smith and M . D . Summers, J . Virol . 39:125-137, 1981) . We evaluated sera from two patients at risk for candidiasis, five patients with systemic candidiasis documented by culture, and two patients who had experienced transient candidemia . Both the specificity and the relative amount of IgG antibodies to C . albicans in each serum sample were readily visualized by this technique, as was the absence of antibody from serum of neonatal and immunocompromised patients . No antibody species appeared to be uniquely associated with candidiasis patients (i.e., each antibody species present in the candidiasis patient was also present in sera of normal individuals or "at-risk" patients) . IgG from rabbits immunized with whole cells or with a cytoplasmic fraction of C . albicans was used to detect C . albicans antigens in patient sera . Although several antigens were detected in the sera from patients with candidiasis, the same antigens were also detected in sera from patients at risk and in normal human serum . No antigens were detected in human serum when preimmune rabbit sera were used . These results suggest that the antigens detected by the rabbit antisera were human serum proteins that cross-reacted with C . albicans antigens . These findings may have important implications in studies of both the pathobiology of C . albicans and the serodiagnosis of candidiasis.

Clin Nephrol, 1985 Dec, 24(6), 310 - 4
Acute tubulo-interstitial nephritis from candida albicans with oliguric renal failure; Ramsay AG et al.; A patient developed candidemia after receiving steroids and antibiotics . Subsequently, acute oliguric renal failure occurred . Renal biopsy showed multiple cortical microabscesses . These contained encapsulated ovoid Candida, budding organisms, short hyphae, and polymorphs . Adjacent tubules showed disruption of the basement membrane, infiltration by polymorphs and necrosis . There was no evidence of pelvic-calyceal obstruction by bezoar . The acute renal failure was attributed to acute candidal tubulo-interstitial nephritis, and was successfully reversed with Amphotericin.

Mycopathologia, 1985 Dec, 92(3), 161 - 7
Inhibition of the differentiation of Candida albicans by the chelator 1,10-phenanthroline; Bedell GW et al.; Several chelators were examined for their ability to prevent the synchronous release of 24- to 48-hour stationary phase singlet cells of the dimorphic yeast Candida albicans into either the mycelial or the budding phenotypes (in a defined liquid medium at 37 degrees C; at pH 6.5 or pH 4.5, respectively) . The only chelator that was found to inhibit mycelium formation completely and to restrict bud formation to about 10% was 1,10-phenanthroline at minimal concentrations of 50 microM and 230 microM, respectively . The inhibition of both phenotypes could be reversed completely by the addition of 200 microM of ZnSO4 . The synchrony of recovery from inhibition by the addition of zinc paralleled that of the controls for both phenotypes, and the final number of mycelia or buds as a percentage of the control was the same (100%) . These findings support the hypothesis that the lag period between the release from stationary phase and the onset of development for Candida represents the time of acquisition of a minimum threshold amount of a cation, such as zinc . The involvement of zinc in phenotypic development is discussed, suggesting that while zinc is involved in the initiation of development, it may not determine the phenotype of Candida albicans.

Am J Hosp Pharm, 1985 Dec, 42(12), 2688 - 91
Amino acid stability and microbial growth in total parenteral nutrient solutions; Parr MD et al.; The stability of amino acids in total parenteral nutrient (TPN) solutions stored for 30 days and the potential for stored TPN solutions to support growth of microbial contaminants were studied . Solutions of 3.5% crystalline amino acids and 25% dextrose with electrolytes were prepared either by using a commercially available amino acid solution with electrolytes or by adding electrolytes individually to a base TPN solution . Solutions were stored in polyvinyl chloride bags at refrigerated (4 degrees C) or room (25 degrees C) temperature for 30 days . Some bags were inoculated with Candida albicans or Pseudomonas maltophilia before storage to serve as positive controls for evaluation of microbial contamination . At appropriate intervals, bags of each type of solution under each storage condition were analyzed for amino acid content . Microbial growth was evaluated by filtering the contents of each bag and incubating the filter in brain-heart infusion broth . No microbial growth was detected in any of the study solutions, but all solutions inoculated with C . albicans and 2 of 16 solutions inoculated with Ps . maltophilia had evidence of growth . No significant decreases in the concentrations of any of the amino acids were noted for solutions stored at refrigerated temperature, but significant decreases in the concentrations of arginine and methionine were noted for solutions stored at room temperature . Total parenteral nutrient solutions can be stored for up to 30 days if they are kept at refrigerated temperatures and protected from light; however, quality assurance measures for these solutions should include end-product microbiologic testing.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1985 Dec, 260(4), 523 - 38
Identification and partial characterization of two proteinases from the cell envelope of Candida albicans blastospores; Ruchel R et al.; As we have communicated previously, the fungal opportunist Candida albicans produces an angiotensin-1 liberating proteinase and a serine proteinase that acts as a converter of the coagulation factor X in vitro (25) . Both enzymes are attached to delipidated cell fragments of fungal blastospores . They copurify upon ion exchange chromatography and gel filtration . The enzymes could be separated by hydrophobic chromatography on Phenylsepharose . According to their substrate and inhibition pattern, the enzymes have been classified as an aspartyl proteinase and a chymotrypsin-like proteinase . Their partial characterization includes estimates of the molecular weight and isoelectric points.

J Gen Microbiol, 1985 Dec, 131 ( Pt 12), 3303 - 10
Ethanol-induced germ tube formation in Candida albicans; Pollack JH et al.; Ethanol is the first reported compound which can induce germ tube formation in Candida albicans without the addition of any nitrogen-containing nutrients . Conditions controlling induction of germ tubes in C . albicans by ethanol were investigated . Ethanol (17.1 mM) in buffered salts solution containing sodium bicarbonate induced 70 to 80% of yeast phase cells of C . albicans to form germ tubes . Germ tubes could be induced by ethanol (0.08 to 340 mM) at temperatures ranging from 29 to 41 degrees C (optimum 37 degrees C) and at pH values ranging from 3.0 to 8.0 (optimum 5.75) . The germ tubes averaged 11 micron in length after 6 h at 37 degrees C . The percentage of cells forming germ tubes decreased as the concentration of cells in the induction solution was increased above 4 X 10(5) cells ml-1 . Germ tubes first appeared 45 to 60 min after continuous exposure to ethanol at 37 degrees C and all cells which formed germ tubes did so by 2 h . Germ tube length decreased as the pH was increased but was independent of the concentration of ethanol . Oxygen was required for germ tube formation . In addition to ethanol, 1-propanol, 2-propanol, 1-butanol and acetic acid could induce germ tube formation, whereas methanol could not . These results indicate that the cells must mobilize their endogenous nitrogen and probably carbohydrate reserves in order to initiate formation of germ tubes . The evidence is inconclusive as to whether ethanol itself must be metabolized for germ tube induction to occur, although it is not thought to act by a nonspecific interaction with the cell membrane.

Immunol Invest, 1985 Dec, 14(6), 503 - 14
Effects of antigens on mononuclear leukocyte chemiluminescence; Wong LS et al.; Influenza virus and Candida albicans allergenic extract elicit alterations in the oxidative metabolic activity of human mononuclear leukocytes (MNL) . MNL preparations (greater than 96% lymphocytes, less than 4% monocytes) exposed in vitro to inactivated influenza virus displayed significantly enhanced oxidative activity, as demonstrated by luminol-amplified chemiluminescence (CL) . MNL from donors who had received influenza vaccine and unimmunized donors showed similar levels of virus-stimulated CL . In contrast, MNL exposed to Candida (a macrophage dependent lymphocyte stimulator) displayed significant suppression in oxidative activity . Our findings support the hypothesis that oxidative activity holds an important role in the early events of the immune response.

Sabouraudia, 1985 Dec, 23(6), 433 - 41
Effect of oxiconazole and Ro 14-4767/002 on sterol pattern in Candida albicans; Polak-Wyss A et al.; The effect of the imidazole oxiconazole and the morpholine derivative Ro 14-4767/002 on the sterol metabolism of Candida albicans was investigated at different periods of growth . Ergosterol, representing the main sterol component of control cells, was markedly reduced in oxiconazole-treated and Ro 14-4767/002-treated cells . However, the total sterol content of the cells treated with both drugs was increased due to accumulation of other sterols not present in control cells: in oxiconazole-treated cells 24-methenedihydrolanosterol, 4,14-dimethylfecosterol and 14-methylfecosterol accumulated, indicating an inhibition of C14-demethylation . This is in agreement with the mode of action described for other azoles in various pathogen fungi . In Ro 14-4767/002-treated cells the main sterol accumulated was ignosterol, indicating an inhibition of delta 14-sterol reductase and delta 8-delta 7-isomerase . This inhibition has not been described before in human pathogens although it has been previously found in plant pathogenic fungi treated with fenpropimorph.

Sabouraudia, 1985 Dec, 23(6), 415 - 24
Suppression of ATP in Candida albicans by imidazole and derivative antifungal agents; Odds FC et al.; Several antifungal agents, at concentrations of 10 micrograms/ml, were shown to suppress ATP concentrations very rapidly in intact cells and spheroplasts of Candida albicans . The highest ATP-suppressing activity was shown by the highly lipophilic imidazole derivatives difonazole, clotrimazole, econazole, isoconazole, miconazole, oxiconazole and tioconazole, which all caused a reduction of cellular ATP content of more than 50% in 10 min . Relatively hydrophilic imidazole derivatives such as ketoconazole were essentially inactive in the test, as were the triazole derivatives fluconazole, ICI 153066, itraconazole and terconazole, and 5-fluorocytosine . Amphotericin B and terbinafine possessed intermediate ATP-suppressing activity, and the dose-response and pH-response curves for these compounds suggested their mechanism of ATP suppression differed from that of the active imidazole derivatives . ATP suppression by azole antifungals did not involve leakage of ATP from the cells and the effect was entirely abrogated by the presence of serum . Intact cells and spheroplasts of yeast-form and hyphal-form C . albicans were generally equally sensitive to ATP suppression, but stationary-phase cells of both morphological forms were less sensitive than exponential-phase cells . The extent of ATP suppression was significantly reduced in stationary-phase yeast cells of a C . albicans strain with known resistance to azole antifungals, but exponential-phase cells of resistant and susceptible strains were equally sensitive . The effect is tentatively ascribed to membrane damage caused directly by the antifungals.

Sabouraudia, 1985 Dec, 23(6), 403 - 6
Resistogram typing of Candida albicans isolates from oral and cutaneous sites in irradiated patients; McCreight MC et al.; Thirteen resistogram strains of Candida albicans were found among isolates obtained from the mouth and cutaneous sites of irradiation of 27 patients receiving treatment for oral and laryngeal cancer . In all cases the yeast was recovered from the mouth before treatment, but not from the skin site until after treatment had begun . Of the 27 patients, 25 harboured one or more strains with identical resistograms in both sites.

Appl Environ Microbiol, 1985 Dec, 50(6), 1509 - 11
Studies on the sensitivity and specificity of the Limulus amebocyte lysate test and rabbit pyrogen assays; Devleeschouwer MJ et al.; The sensitivity and specificity of the Limulus amebocyte lysate test and rabbit pyrogen assay were studied by means of artificially contaminated parenterals . Various gram-negative and gram-positive bacterial strains were used as was one strain of the yeast Candida albicans . The numbers of organisms needed to elicit positive responses in distilled water and normal saline were recorded and compared . The sensitivity and specificity of the Limulus amebocyte lysate assay for the detection of bacterial endotoxin from gram-negative bacteria were demonstrated . Variable results were recorded with gram-positive bacteria and Candida albicans.

Mycopathologia, 1985 Dec, 92(3), 141 - 7
{Use of a method of lipid extraction from Candida albicans cell walls blastospores . Ultrastructural implications concerning their localization and parietal microfibril organization}; Poulain D et al.; A chemical method for lipid extraction has been applied to Candida albicans blastospores previously to their examination by transmission electron microscopy . The results led to the concept of a superficial location of lipids bounded to the peptidopolysaccharidic matrix of the cell wall . This lipid extraction also allowed us to describe cell wall microfibrillar structures . Two types of microfibrills have been particularly identified: microfibrils of approximately 50 A in diameter, involved in a network of the cell wall intermediate layers and supposed to correspond to beta 1-3 glucans; fibrillar structures of 120 A in diameter, similar to chitin microfibrils, observed in the bud scar septum.

Br J Surg, 1985 Dec, 72(12), 967 - 9
The mycotic flora in proctological patients with and without pruritus ani; Dodi G et al.; The perianal mycotic flora was studied in proctological patients with and without pruritus ani, as well as in control subjects . Four groups of patients underwent perianal mycoculture . In Group 1, 53 patients with anal pruritus were treated for benign anorectal disease . In Group 2, 24 patients with no underlying disease presented with anal pruritus . Both of these groups underwent concomitant chemical and parasitical examination of the faeces and an oral glucose tolerance test . In Group 3, 50 patients without pruritus ani at present or in the past were treated for benign anorectal diseases . In Group 4, 47 surgical patients without pruritus ani were treated for benign (9) and malignant (38) non-proctological diseases . In Group 1 the mycoculture was positive in 24/53 patients (Candida albicans 14, dermatophytes 10) . In Group 2 fungal infections were seen in 16/24 patients (C . albicans 7, dermatophytes 9) . No parasites or diabetes were found in either group . In Group 3 C . albicans was isolated in 14/50 patients . In Group 4 C . albicans was found in 11/47 cases (2 in benign, 9 in malignant diseases) . Infection by C . albicans was observed in all groups studied, independent of the presence of disease or anal pruritus . The presence of dermatophytes was always associated with pruritus ani.

Br J Obstet Gynaecol, 1985 Dec, 92(12), 1267 - 71
The relation between vaginal pH and the microbiological status in vaginitis; Hanna NF et al.; The vaginal pH, microbial flora and presence of clue cells were investigated in 89 women who were seen at a sexually transmitted diseases clinic with a vaginal discharge or because they were contacts of men with gonococcal or non-gonococcal urethritis or because they were seeking a routine examination . None of the women had received antibiotics for at least 4 weeks before examination . A clinically normal vaginal secretion was found in 21 (55%) of 38 women who had a vaginal pH of 5.0-5.5, while such a secretion was found in only 7 (14%) of 51 women who had a pH value of 6.0-7.5 . Clue cells, Chlamydia trachomatis and Mycoplasma hominis were found two to three times more often in women with the higher pH value than in those with the lower value and Ureaplasma urealyticum and Trichomonas vaginalis also occurred more frequently in the former group . Furthermore, large numbers of M . hominis organisms (greater than or equal to 10(6) colour changing units/ml) were associated significantly with the higher pH value . However, there was no appreciable difference in the distribution of Candida albicans between the two groups . C . trachomatis but not the other micro-organisms was isolated most often from women who were taking oral contraceptives . The results indicate that a pH of greater than or equal to 6.0 is strongly predictive of infection and may be more useful than the type of discharge in suggesting a need for confirmatory microbiological tests.

J Med Microbiol, 1985 Dec, 20(3), 283 - 90
Experimental candidosis: paw oedema in the analysis of a local infection; Miller TE et al.; Existing models of Candida albicans infection are semi-quantitative and do not allow continuous observations to be made on individual animals . We have used the inflammatory response in the footpad as an indirect measure of the number of yeast cells in a localised lesion . C . albicans infection of the footpad has been used in series of experiments in which changes in yeast-cell numbers in the local lesion have been compared with the degree of footpad oedema . Studies in animals treated with cyclophosphamide or amphotericin have confirmed that paw oedema parallels yeast-cell numbers in the local lesion . This quantitative approach will be helpful in the study of localised infection with C . albicans and other fungi and in the evaluation of antifungal agents.

J Infect Dis, 1985 Dec, 152(6), 1264 - 74
Adherence of Candida to cultured vascular endothelial cells: mechanisms of attachment and endothelial cell penetration; Rotrosen D et al.; To elucidate the pathogenesis of hematogenous Candida infections, we developed an in vitro model of Candida adherence to and penetration of human endothelial cells . We enhanced or inhibited adherence in order to probe mechanisms of attachment . Adherence of Candida albicans showed a linear relation to Candida inoculum (range, 10(2)-10(5) cfu, r = .99, P less than .01) and exceeded that of less virulent Candida species and that of Saccharomyces cerevisiae (P less than .01) . Candida immune serum blocked attachment (greater than 95% inhibition; P less than .001), however, this activity was abolished by immunoprecipitation of immune serum with C . albicans mannan (P less than .001) and was unaffected by immunoprecipitation with S . cerevisiae mannan or by adsorption with particulate chitin . Adherence was diminished by exposing C . albicans to heat (greater than 99% inhibition; P less than .01), UV light (98% inhibition; P less than .01), or sodium periodate (greater than 72% inhibition; P less than .01) . An extract from heat-exposed C . albicans blocked adherence (greater than 51% inhibition; P less than .001) . Transmission electron microscopy demonstrated that viable or killed Candida organisms were attached to endothelial cells, were enveloped by membrane processes from the endothelial cell surface, and were incorporated into the endothelial cells within phagosomes . Cytochalasin B blocked incorporation without blocking surface attachment.

J Nucl Med, 1985 Dec, 26(12), 1377 - 81
Comparison of bone and gallium-67 imaging in heroin users' arthritis; Bittini A et al.; Nine cases of primary septic arthritis in heroin addicts are reported . Fibrous and cartilaginous joint localizations are prominent (four sternoarticular, three sacroiliac, one sacroccocygeal, and one knee) . In all patients but one, conventional roentgenographic studies were negative . In six cases the causative agent was Staphylococcus aureus and in two cases, Candida albicans . In one case, it could not be determined . Our clinical observations, correlating the radioisotopic studies, suggest that in the first week of evolution the diagnostic procedure of choice is the {67Ga}citrate scintigram . Indeed, during this period the {99Tc}MDP bone scan is usually negative . The early demonstration and localization of the disease, together with the rapid bacteriologic diagnosis, allows for an early and more appropriate antibiotic treatment and better results.

Arch Biochem Biophys, 1985 Dec, 243(2), 338 - 48
Immunochemical study on the mannans of Candida albicans NIH A-207, NIH B-792, and J-1012 strains prepared by fractional precipitation with cetyltrimethylammonium bromide; Shibata N et al.; The mannans of Candida albicans NIH A-207 (A strain, serotype A), C . albicans NIH B-792 (B strain, serotype B), and C . albicans J-1012 (J strain, serotype C) prepared by fractional precipitation with cetyltrimethylammonium bromide (Cetavlon) were investigated for their immunochemical properties . Upon treatment with 10 mM HCl at 100 degrees C for 60 min, the mannans of A and B strains each released a mixture of manno-oligosaccharides ranging from hexaose to mannose together with (for each one) an acid-modified mannan, while J-strain mannan released lower oligosaccharides, tetraose to mannose . The acid-modified mannan of B strain did not show antibody-precipitating activity against homologous antiserum, whereas acid-modified A- and J-strain mannans retained most of this activity . The acid-released oligosaccharides were assumed to consist of beta-1,2-linked D-mannopyranosyl residues from the results of specific rotation and proton magnetic resonance studies.

Antimicrob Agents Chemother, 1985 Dec, 28(6), 815 - 8
Efficacy of UK-49,858 (fluconazole) against Candida albicans experimental infections in mice; Troke PF et al.; UK-49,858 (fluconazole), a new, orally absorbed bis-triazole derivative, has been evaluated against systemic infections with Candida albicans in normal and immunosuppressed mice and against an intestinal infection with C . albicans in immunosuppressed mice . Orally administered ketoconazole was used as a comparison agent throughout, and orally administered amphotericin B was included for comparative in the experimental intestinal infection . In a 10-day dosage regimen, UK-49,858 was far more active than ketoconazole against systemic infections with C . albicans in normal and immunosuppressed mice . In normal mice, extension of UK-49,858 dosing to 30 days resulted in prolongation of survival to over 90 days, and up to 60% of treated animals had no detectable C . albicans in their kidneys . In addition, over 90% of mice with intestinal candidiasis had culture-negative feces after a 3-day treatment with UK-49,858, but only 62 and 23% of mice gave this response after amphotericin B and ketoconazole therapy, respectively . These data suggest that UK-49,858 may be of value in the treatment of systemic and gastrointestinal infections due to C . albicans in humans.

Transplantation, 1985 Dec, 40(6), 694 - 7
Dietary nucleotides, a requirement for helper/inducer T lymphocytes; Van Buren CT et al.; Previous investigations have revealed that dietary nucleotide restriction delays the onset of primary murine cardiac allograft rejection and acute graft-versus-host disease followed H-2-incompatible bone marrow transplantation, suppresses sensitization to intradermally injected antigens and suppresses in vivo and in vitro lymphocyte proliferation to alloantigen or lectin stimulation . To determine the mechanisms responsible for these phenomena, BALB/c mice were placed on chow (F), nucleotide free (NF) diet, or NF diet supplemented with 0.25% RNA (NFR), with 0.6% adenine (NFA), or with 0.06% uracil (NFU) . Following four weeks of dietary equilibrium, splenic lymphocytes harvested from naive or immunostimulated mice in the various dietary groups were stained with monoclonal antibodies directed Lyt 1, Lyt 2, 3, or surface mouse immunoglobulin (IgG) surface markers . While naive animals demonstrated no differences in lymphocyte subpopulations between groups, following complete Freund's adjuvant (CFA) stimulation, splenic lymphocytes for NF mice demonstrated 27.3 +/- 1.7% Lyt 1+ cells compared with F (32.6 +/- .04%) and NFR mice (33.2 +/- 1.2%) (P less than 0.02) . Restriction of dietary nucleotides affected not only phenotypes of T lymphocytes, but also T cell function . Following conconavalin A stimulation of irradiated splenic lymphocytes, IL-2 production was decreased in NF mice compared with the F control group (P less than 0.01) . The RNA-repleted diet maintained normal IL-2 production, while addition of adenine or uracil alone did not . Finally, NF diets adversely affected host resistance to the opportunistic pathogen Candida albicans . Following inoculation with 0.25 X 10(6) organisms NF or NFA-fed hosts succumbed more rapidly than F, NFR, or NFU fed hosts (P less than 0.001) . These data suggest that helper/inducer T lymphocytes require exogenous nucleotides to respond normally following immune stimulation . Uracil may be the critical substrate, based upon the studies of Candida resistance . By understanding the metabolic basis of NFD-induced immunosuppression, the role of dietary nucleotides in combatting infection and alloantigen rejection can be more clearly defined.

J Hosp Infect, 1985 Dec, 6(4), 398 - 405
Adhesive tapes in the special care baby unit; Marples RR et al.; Semi-quantitative sampling of 37 taped sites and 37 matching control sites in 30 babies in a special care baby unit showed a tendency for bacterial growth under the cardiac monitors or the occlusive plastic adhesive tape to be greater than at the control site . This tendency was demonstrable even when potential pathogens were considered . During the study, an outbreak due to Candida albicans occurred . Antibiotic resistance of coagulase-negative staphylococci was marked and this, and other evidence, suggested that part of the skin flora was acquired from the unit.

Acta Med Okayama, 1985 Dec, 39(6), 441 - 6
Comparison of basophil histamine release induced by the cross-linking of IgE receptors; Tanizaki Y et al.; Basophil histamine release induced by allergens (house dust and Candida albicans) and anti-IgE was examined in 31 patients with bronchial asthma in relation to patient age, age at onset of the disease and serum IgE levels . Basophils from patients under 40 years of age generally released a significantly large amount of histamine by stimulation with house dust and anti-IgE . On the other hand, histamine release from patients over 41 years of age was generally not marked when the cells were incubated with house dust and anti-IgE, although, in some cases, the release induced by C . albicans was fairly marked . Basophils from patients under 30 years of age at onset were reactive to house dust and anti-IgE, while the cells from patients over 41 years of age at onset tended to be reactive only to C . albicans . Basophils from patients with low serum IgE levels were less reactive than the cells from patients with high levels of IgE to house dust and anti-IgE . C . albicans-induced release of histamine did not correlate with serum IgE levels.

Am J Ophthalmol, 1985 Nov 15, 100(5), 719 - 23
Calcofluor and ink-potassium hydroxide preparations for identifying fungi; Arffa RC et al.; Calcofluor and ink-potassium hydroxide preparations identified Fusarium solani, Aspergillus fumigatus, and Candida albicans, the three most common ocular fungal pathogens, in scrapings, biopsy specimens, and tissue sections of corneal mycotic infections in rabbits . These stains also identified fungal organisms in specimens from four human patients with keratomycoses . Neither procedure requires more than a few minutes to perform or extensive training or experience to interpret . The specimen stained with calcofluor can be examined immediately, but may not identify all fungi . The more sensitive ink-potassium hydroxide preparation should be examined after 18 to 24 hours, and is less likely to provide false-positive results than the calcofluor method.

Biochem Biophys Res Commun, 1985 Nov 15, 132(3), 1160 - 5
Effect of temperature on siderophore production by Candida albicans; Ismail A et al.; The purpose of this study was to examine the effect of elevated temperature on growth and siderophore production by Candida albicans . The results showed that an increase in incubation temperature from 37 degrees C to 41 degrees C produced a marked decrease in both the rate and quantity of siderophore production . Elevated temperature was unable to suppress growth of C . albicans in either a control culture medium or a deferrated culture medium . A significant suppression of growth compared to the controls was observed in the deferrated media at both 37 degrees C and 41 degrees C . However with time, the growth of cells in the deferrated media showed partial recovery which was followed by an increase in siderophore production . Thus, elevation of temperature to suppress growth and siderophore production by C . albicans appears to be an ineffective host defense mechanism.

Science, 1985 Nov 8, 230(4726), 666 - 9
High-frequency switching of colony morphology in Candida albicans; Slutsky B et al.; The pathogenic yeast Candida albicans switches heritably and at high frequency between at least seven general phenotypes identified by colony morphology on agar . Spontaneous conversion from the original smooth to variant phenotypes (star, ring, irregular wrinkle, hat, stipple, and fuzzy) occurs at a combined frequency of 1.4 X 10(-4), but is increased 200 times by a low dose of ultraviolet light that kills less than 10 percent of the cells . After the initial conversion, cells switch spontaneously to other phenotypes at a combined frequency of 2 X 10(-2) . Switching is therefore heritable, but also reversible at high frequency . The genetic basis of this newly discovered process and its possible role in Candida pathogenesis are considered.

Am J Clin Pathol, 1985 Nov, 84(5), 598 - 602
Granulomatous inflammation in the acquired immune deficiency syndrome; Jagadha V et al.; Granulomas were found in 16 biopsied specimens from eight patients with the acquired immune deficiency syndrome (AIDS), a disease characterized by a profound suppression of the T-cell arm of immunity . The pathogens were Mycobacterium avium-intracellulare (1), Mycobacterium tuberculosis (3), Histoplasma capsulatum (2), Candida albicans (1), and unidentified in one patient . The sites of granuloma formation included the lung in two, the pleura in one, the liver in three, the bone marrow in six, the skin in one, and the lymph node in three cases . The granulomas were epithelioid in nature, with aggregates of epithelioid histiocytes and macrophages . They were by and large small and loosely formed, with minimal or absent lymphocytic cuffing . Although it is a well-recognized concept that T-cell and macrophage interaction plays an important role in the granulomatous inflammatory response, granulomas have been produced in experimental animals independent of cell-mediated immune mechanisms . Granuloma formation in AIDS patients may well represent a clinical example of such a phenomenon.

Antimicrob Agents Chemother, 1985 Nov, 28(5), 643 - 7
Effect of the imidazole derivative lombazole on the ultrastructure of Staphylococcus epidermidis and Candida albicans; Barug D et al.; Lombazole, an antimicrobial agent of the imidazole class, induced profound ultrastructural changes in Staphylococcus epidermidis and Candida albicans, as observed by freeze fracture electron microscopy . In S . epidermidis cells, the primary effect on ultrastructure was characterized by a distinct change in the morphology of the plasma membrane . Secondary effects of lombazole were cell wall thickening, accumulations of lipidlike material, abnormal cell division, severe change of shape, separation of the plasma membrane from the cell wall, and disruption of cells . The alterations in C . albicans were characterized by the deformation of and a decrease in the number of invaginations in the protoplasmic fracture face and corresponding ridges on the exoplasmic fracture face and by separation of the plasma membrane from the cell wall, leaving a gap which frequently contained small vesicles . Moreover, a considerable thickening of the cell wall occurred at localized regions . These structural alterations are discussed in relation to biochemical changes which may correlate with these phenomena.

Farmaco {Sci}, 1985 Nov, 40(11), 803 - 7
Antimycotic 2-alkyldithio, 2-aralkyldithio, 2-aryldithiobenzamides; Modena T et al.; Some 2-alkyldithio, 2-aralkyldithio, 2-aryldithio benzoic acids, their methyl esters and N-monosubstituted amides were prepared and tested in vitro against Candida albicans and Trichophyton mentagrophytes . Some N-monosubstituted amides displayed activities similar to those of clotrimazole and pyrrolnitrin . Against Candida albicans, N-monosubstituted amides exhibited a generally higher activity than the corresponding N-monosubstituted amides of 2,2'-dicarboxydiphenyldisulfide.

Vet Immunol Immunopathol, 1985 Nov, 10(2-3), 131 - 46
Monocyte function in rhesus monkeys with simian acquired immune deficiency syndrome; Legrand EK et al.; Monocyte function in rhesus monkeys with simian acquired immune deficiency syndrome (SAIDS) was compared with that in age-matched normal juvenile rhesus monkeys . The functional tests were 1) chemotaxis, 2) phagocytosis of opsonized Candida albicans, 3) killing and/or growth inhibition of Candida albicans, 4) generation of respiratory burst, and 5) monocyte-derived macrophage response (morphology and/or respiratory burst) to stimulating agents such as lymphokines, gamma interferon, endotoxin, and phorbol myristate acetate . The monkeys tested had either clinical SAIDS (alive with lymphadenopathy, splenomegaly, and lymphopenia or neutropenia) or had terminal SAIDS (moribund due to the disease) . Responses of monocytes from 14 monkeys with clinical SAIDS were indistinguishable from those of 9 normal juvenile rhesus monkeys, whereas monocytes from 3 monkeys with terminal SAIDS had enhanced phagocytosis and respiratory burst capacity . Chemotaxis, candidacidal/stasis activity, and response to stimulating agents were normal in these terminal cases . Plasma from the SAIDS monkeys was as capable of opsonizing yeasts and of being able to generate chemotactic factors by endotoxin as was control plasma . SAIDS retrovirus (SRV) was detected by co-cultivation of pure monocyte-derived macrophage cultures with Raji cells, an indicator cell line which forms syncytia in the presence of SRV . Four terminal SAIDS cases and one late-stage clinical SAIDS case were virus-positive when the number of macrophages in the cultures ranged from less than 50 to about 500 . Terminal SAIDS monocyte-derived macrophages in culture as long as 17 days produced SRV . These data show that in monkeys with SAIDS the major effector functions of monocytes and macrophages involved in host defense are intact (even up until death) . Additionally, some of the monocytes are productively infected, and these infected monocytes are viable and adherent in culture.

Pathol Biol (Paris), 1985 Nov, 33(9), 911 - 3
{Intrathecal synthesis of specific antibodies in Candida albicans meningoencephalitis}; Vilella JM et al.; Titration of IgG, albumin, and specific antibodies, both in serum and CSF, during the course of a Candidal meningoencephalitis allowed to demonstrate intrathecal synthesis of specific IgG antibodies against C . albicans.

Mycopathologia, 1985 Nov, 92(2), 93 - 9
Experimental pulmonary candidiasis in modified rabbits . II . Immunohistochemical evidence of participation of immune complexes in the formation of fungal lesions in C . albicans-sensitized hosts; Nakamura T; Pulmonary lesions induced by an intratracheal inoculation of Candida albicans into rabbits in untreated control, bovine serum albumin (BSA)-sensitized and C . albicans-sensitized groups were examined immunohistochemically to clarify the localization of IgG, IgM and C3 . In the control group no inflammatory cells were immunoreactive for IgG and only a few macrophages for IgM and C3, whereas in the BSA- and C . albicans-sensitized groups there were a small number of IgG-positive polymorphonuclear leukocytes and IgM- and C3-positive macrophages in the lesions, the latter group being more prominent . Furthermore, epithelioid granulomatous lesions at the late stage in the C . albicans-sensitized animals showed scattered epithelioid cells containing IgG as well as abundant IgG- and IgM-positive plasma cells . These immunohistochemical results were considered to support the estimation that immune complexes contributed to the modification of fungal lesions in the C . albicans-sensitized hosts, although non-immunological defense mechanisms seemed to be more important in the elimination of the fungus.

Mycopathologia, 1985 Nov, 92(2), 73 - 6
Candida endophthalmitis after heroin abuse; Malecaze F et al.; Three cases of ocular candidosis involving heroin abusers have been observed in 1983 in Toulouse department of ophthalmology . These three patients had used iranian brown heroin . Twenty similar cases have been published in these last years . This new pathology can be explained on two reasons . The first is that the drug abusers have some immunity pertubation; however, immunity exploration in these patients does not reveal any immunodeficiency . The second reason, certainly more important, is the method of using heroin . The diagnosis of Candida endophthalmitis of course based on clinical context must be proved by biological tests . Candida albicans is never identified in aqueous humor . For this reason, it seems very interesting to detect anti-candida antibodies in aqueous humor . It has been used as methods of dosage laser Nephelemetry for IgG and immunofluorescence for candidosis antibodies . The criterion used is similar to the toxoplasmosis coefficient established by Desmonts (3) . In two cases, this test was the only way that permits us to have certitude of candidosis ocular diagnosis . Otherwise the observations show that anterior chamber punction is more significant when there is an anterior uveitis.

Mycopathologia, 1985 Nov, 92(2), 121 - 3
Nutritional enrichments do not affect growth or stability of heterokaryons of Candida albicans; Sarachek A et al.; Complex nutritional supplements which stimulate growth of monokaryons of Candida albicans have no effect on growth or stability of heterokaryons . This evidence that heterokaryotic growth is characteristically limited by something other than nutritional circumstances is consistent with prior indications of naturally dysfunctional ribosomes in heterokaryons.

J Invest Dermatol, 1985 Nov, 85(5), 438 - 40
A specific inhibitor of keratinolytic proteinase from Candida albicans could inhibit the cell growth of C . albicans; Tsuobi R et al.; The authors investigated the influence of culture medium pH and various kinds of protease inhibitors on the growth of Candida albicans when cultivated in liquid medium containing human stratum corneum (HSC) as the nitrogen source . Rapid growth of C . albicans was observed with weakly acidic media, particularly at pH 4.0 . From among the various kinds of protease inhibitors added to the media at pH 4.0, pepstatin, a carboxyl protease inhibitor, most strongly inhibited the growth of C . albicans dependent upon its concentration . The antifungal effect of pepstatin was not fungicidal, but was nevertheless effective even at a very low concentration of 0.01 microgram/ml . This inhibitory effect of pepstatin was considerably stronger than that of the well-known antifungal agent, clotrimazole . Pepstatin is a specific inhibitor of keratinolytic proteinase (KPase) from C . albicans; it belongs to the carboxyl proteinases group and has an optimum pH at 4.0 . Pepstatin showed a strong antifungal effect, possibly through KPase inhibition, in biologic (HSC) medium that was similar to that encountered in vivo . Our results suggest that KPase may play an important role in the growth of C . albicans and that pepstatin has the possibility of being used as a new type of antifungal agent.

J Invest Dermatol, 1985 Nov, 85(5), 434 - 7
Effects of antifungal agents on ergosterol biosynthesis in Candida albicans and Trichophyton mentagrophytes: differential inhibitory sites of naphthiomate and miconazole; Morita T et al.; The effects of naphthiomate and miconazole showing ergosterol biosynthesis inhibition on Candida albicans and Trichophyton mentagrophytes were investigated by measuring {14C}acetate incorporation into sterols and its precursors . Naphthiomate, like allylamine compounds, was found to interfere with fungal ergosterol biosynthesis by preventing the conversion of squalene into squalene epoxide which is mediated by squalene epoxidase . This metabolic inhibition resulted in a considerable decrease of ergosterol with a corresponding increase of squalene, which is more distinct in T . mentagrophytes than in C . albicans . This indicates that naphthiomate blocks the utilization of squalene by inhibition of squalene epoxidation; unlike N-substituted imidazole, miconazole has been known to inhibit ergosterol formation by inhibiting C14-demethylation . In addition, it is of interest to note that miconazole causes a great accumulation of lanosterol in C . albicans cells, while in T . mentagrophytes cells there was instead a drastic increase of 24-methylenedihydrolanosterol but not lanosterol . The results obtained from this study indicate that repression of ergosterol synthesis by naphthiomate and miconazole is due to inhibition of squalene epoxidation for the former and C14-demethylation for the latter.

J Clin Microbiol, 1985 Nov, 22(5), 861 - 2
New germ tube induction medium for the identification of Candida albicans; Berardinelli S et al.; A new germ tube induction medium, composed of three parts Rabbit Coagulase Plasma with EDTA (BBL Microbiology Systems) and two parts Tryp-Soy broth (Scott Laboratories, Inc.), was effective for the presumptive identification of Candida albicans . This medium was safer to use, more accurate, and less expensive than other commercial germ tube induction media.

J Clin Microbiol, 1985 Nov, 22(5), 745 - 7
Quantification of medically important Candida species and Torulopsis glabrata by a spiral inoculation system: correlation with pour plate and spread plate methods; Walsh TJ et al.; A new method of quantifying Candida spp . and Torulopsis glabrata suspensions, the spiral inoculation system, was studied to compare its accuracy, efficiency, and cost with the standard pour plating and spread plating methods . Concentrations of yeast suspensions ranging from 10(2) to 10(5) CFU were quantified simultaneously by the three methods . Linear regression analysis was used to determine the correlation between the spiral inoculation system and pour plating and between the spiral system and spread plating for Candida albicans, C . tropicalis, C . krusei, and T . glabrata . Spiral system and pour plating techniques correlated very well for all species, as did the spiral system and spread plating techniques (r greater than 0.95; P greater than 0.001).

Infect Immun, 1985 Nov, 50(2), 541 - 4
Pathogenicity of morphological and auxotrophic mutants of Candida albicans in experimental infections; Shepherd MG; The relative pathogenicities of yeast and mycelial forms of Candida albicans were determined after intravenous injection of the two forms into mice . Yeast and mycelial forms of C . albicans CMI45348 were prepared in chemostat culture . Both morphological forms were pathogenic, but the histology of kidney sections always showed a mixture of the yeast and mycelial elements of the organism . Similarly, infection of mice with prototrophic strains produced a mixture of morphological forms at the site of infection . The yeast (CA2) and mycelial (hOG301) morphological mutants of C . albicans were pathogenic, and sections from the kidneys of the infected mice showed that the mutants retained their original morphological forms . These data indicate that both the yeast and mycelial forms of C . albicans can adhere, invade, and proliferate in an infected host . Auxotrophic diploid mutants were nonpathogenic . However, construction of a prototrophic tetraploid strain from two auxotrophs restored the pathogenicity of the organism.

Infect Immun, 1985 Nov, 50(2), 598 - 600
Candida albicans and Candida stellatoidea, in contrast to other Candida species, bind iC3b and C3d but not C3b; Heidenreich F et al.; It was demonstrated that complement-coated sheep erythrocytes bind to Candida albicans cells grown in serum-free RPMI 1640 medium . Testing of purified complement components proved that iC3b and C3d were responsible for the reaction, whereas C3b and C3b-H reacted only slightly if at all . Binding occurred only to C . albicans and C . stellatoidea, not to other species pathogenic to humans . There was evidence of a lectinlike nature of the effect.

J Infect Dis, 1985 Nov, 152(5), 938 - 45
A rapid colorimetric assay of fungal viability with the tetrazolium salt MTT; Levitz SM et al.; A rapid colorimetric assay for viability of fungi that uses the tetrazolium salt MTT is described . All live species of a wide range of medically important fungi that were tested reduced MTT, with resultant intracellular formation within several hours of clearly visible purple crystals of MTT-formazan . The assay proved particularly useful in measuring viability of individual hyphae; greater than 99% of live Aspergillus fumigatus and Rhizopus oryzae hyphae stained purple when incubated with MTT compared with 0% of hyphae killed by any of a variety of methods . The MTT method for measuring fungal viability closely correlated with a slide-culture technique when killing of A . fumigatus hyphae by graded concentrations of hydrogen peroxide was compared . MTT-formazan was easily extracted from the fungi by alcohol, a procedure allowing spectrophotometric quantification of fungal killing in both cell-free and cellular systems . A linear relation between inocula and MTT reduction of several fungi, including Candida albicans blastospores and A . fumigatus hyphae, was demonstrated . Human leukocytes killed 80.3% of C . albicans blastospores as measured by the MTT assay, compared with 70.5% as measured by dilutions and pour plates . Killing of A . fumigatus hyphae by human leukocytes was also quantitated by using the MTT assay.

J Immunol Methods, 1985 Oct 10, 82(2), 267 - 80
A reverse passive latex agglutination test for the diagnosis of systemic candidosis; Burnie J; A new reverse passive latex agglutination test for the detection of serum antigen in systemic Candida albicans infection is reported . 1700 sera were examined from 91 patients who had either proven or suspected systemic candidosis, 183 patients who were colonized and 636 patients with no evidence of candidal infection . Thirty of the systemically infected patients had lymphoproliferative disorders and the rest a variety of surgical or medical diseases with no underlying neutropenia . The latex particles were sensitised with an antiserum raised in rabbits against a pressate of Candida albicans . The degree of antigenaemia was proportional to the likelihood of invasive disease such that a diagnostic cut-off point of 1 in 8 produced a test for systemic candidosis with a sensitivity of 90% and specificity of 80.4% in patients with lymphoproliferative disorders . In the remaining medical and surgical patients a diagnostic cut-off point of 1 in 10 produced a test with a sensitivity of 96.7% and specificity of 98.8% . The patients with lymphoproliferative disorders tended to produce lower serum antigen levels . The sera were also assayed for antibody using latex particles sensitised with pressate.

Antimicrob Agents Chemother, 1985 Oct, 28(4), 511 - 3
Prophylaxis of murine candidiasis via application of liposome-encapsulated amphotericin B and a muramyl dipeptide analog, alone and in combination; Mehta RT et al.; The present study was conducted to examine the effect of a lipophilic analog of muramyl dipeptide, 6-O-stearoyl-N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine (6-O-S-Abu-MDP), a macrophage activator, on the prophylactic activity of liposomal amphotericin B (L-AmpB) against disseminated candidiasis in mice . Multilamellar vesicles containing AmpB and (6-O-S-Abu)-MDP were prepared by using dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (7:3 molar ratio) . Hale-Stoner mice (6 to 8 weeks old) were injected with 7 X 10(5) CFU of Candida albicans 336 isolated from a patient . Groups of mice were injected intravenously with different doses of L-AmpB and L-(6-O-S-Abu)-MDP, individually or in combination, 2 days before challenge with C . albicans . The mice were injected with a fixed dose of L-AmpB (1.2 mg/kg in 400 mg of lipid per kg) and various doses of L-(6-O-S-Abu)-MDP (0.6, 1.2, 2, and 4 mg/kg in 400 mg of lipid per kg) or vice versa . Other control groups included untreated mice and those receiving empty liposomes (400 mg of lipid per kg), free AmpB (0.6 mg/kg), or free (6-O-S-Abu)-MDP (4 mg/kg) . The mice receiving L-AmpB (1.2 mg/kg) plus L-(6-O-S-Abu)-MDP (0.6 to 4.0 mg/kg) survived up to 25 to 30 days as compared with those injected with L-AmpB alone (15 days) or with L-(6-O-S-Abu)-MDP alone (10 to 15 days) . All the mice in other control groups died within 7 to 11 days . The kidney cultures of the mice that received L-AmpB (4 mg/kg) plus L-(6-O-S-Abu)-MDP (1.2 mg/kg) were free of C . albicans infection, unlike those injected with L-AmpB . Variance analysis of these findings indicates a synergistic activity between L-AmpB and L-(6-O-S-Abu)-MDP in the prophylaxis of candidiasis.

Am Rev Respir Dis, 1985 Oct, 132(4), 752 - 6
Detection of histoplasmal antigens in mice undergoing experimental pulmonary histoplasmosis; Graybill JR et al.; A micro-ELISA assay was developed for the quantitation of Histoplasma capsulatum antigen in lungs, bronchoalveolar lavage fluid (BALF), and serum of intranasally infected mice . As little as 0.2 ng of antigen/ml could be detected . During the course of experimental histoplasmosis, immunologically intact, thymus-containing mice (nu/+) had detectable histoplasmal antigens in their lungs, serum, and BALF within 1 day of challenge . Lung, BALF, and serum antigen concentration rose to a peak 2 wk after challenge; in nu/+ mice, antigen concentration then declined through the next 2 wk . In contrast, athymic nude mice have depressed cell-mediated immunity; their antigen concentration continued to rise throughout the course of progressive, ultimately lethal, illness . Antigen concentrations correlated with quantitative cultures of the lungs and BALF . There was little cross reactivity in mice challenged intranasally with Candida albicans or Blastomyces dermatitidis . The sensitivity of this test, and the apparently minimal cross reactivity, suggest that the micro-ELISA for histoplasmal antigen might have significant clinical application in diagnosing and monitoring the course of histoplasmosis.

South Med J, 1985 Oct, 78(10), 1262 - 3
Septic phlebitis caused by Candida albicans and diagnosed by needle aspiration; Yackee JM et al.; We have described a patient who had Candida albicans suppurative thrombophlebitis at the site of an indwelling intravenous catheter . The microbial etiology was established by needle aspiration of the venipuncture site, affording rapid and accurate identification of the infecting organism and providing prompt institution of therapy . Phlebectomy and a brief course of amphotericin B prevented further dissemination of the infection.

Int J Oral Surg, 1985 Oct, 14(5), 416 - 27
Oral findings in irradiated edentulous patients; Bernhoft CH et al.; 11 edentulous patients (mean age 71.2 years) with oral or oropharyngeal malignancies were examined clinical and microbiologically before, during, and after receiving tumoricidal radiation doses (26.4-74 Gy) towards the head and neck regions . The effect of a supervised oral hygiene program and a saliva substitute (Va-OraLube) was studied . The 9 patients who survived the observation period, showed increased xerostomia and mucositis related to increased radiation . Radionecrosis or oral infections were not observed . The patients wore their dentures throughout the observation period and preferred to use the saliva substitute . The initial number of acidophilic bacteria was high, Candida albicans were present in low numbers and enteric bacteria occurred more frequently than normally . There was a reduction of micro-organisms after introduction of the hygiene program . It is concluded that careful planning of the radiotherapy, pre-radiation oral examination, denture control and instruction and an effective oral hygiene program are essential for the reduction of oral complications in edentulous patients receiving tumoricidal radiotherapy to the head and neck regions.

Infect Immun, 1985 Oct, 50(1), 82 - 90
Effects of carbon dioxide and pH on adhesion of Candida albicans to vaginal epithelial cells; Persi MA et al.; A controlled-environment membrane model for use in vitro was developed and employed in an attempt to mimic the environment of the vagina in order to study yeast-vaginal cell adhesion . Adhesion in vitro of four strains of Candida albicans (NIH 3181A, NIH 526B, ATCC 18804, and MCO 2400) to vaginal epithelial cells (VEC) appeared to be affected by the pH and the level of carbon dioxide that have been found to be present in the vagina in vivo . Strain 3181A had a greater adhesion ability than 526B when the concentration of yeast cells was increased and when the yeast cells were incubated with VEC at pH 5 in sodium phosphate buffer in ambient air supplemented with 10% CO2 . Of the four strains of C . albicans used, 3181A had the greatest adhesion ability, with strains 2400, 18804, and 526B ranked in order of decreasing adhesion ability . Also, an enhanced, electron-dense, matted outer region of the cell walls of the yeasts was observed frequently when they were incubated in ambient air supplemented with 10% CO2 . In addition, of the vaginal cells that had yeast cells attached to them, an average of 94.4% of the total yeast cells were attached to the microridge side of the VEC, whereas an average of only 5.6% of the total were found on the nonmicroridge side of the VEC . The results from this study indicate that adhesion of C . albicans to the VEC surface was affected by the strain of yeast used, by the side of the vaginal cell exposed, and by the pH and CO2 levels present in the adhesion assay.

Antimicrob Agents Chemother, 1985 Oct, 28(4), 494 - 9
Relative rates of transport of peptidyl drugs by Candida albicans; McCarthy PJ et al.; A variety of peptide drugs are known to be active against Candida albicans; however, little is known about the transport of such agents into the target organism . To provide further information concerning transport of this type, we studied the uptake of two classes of small linear peptides: polyoxins which act intact within the cell and the m-fluorophenylalanyl (m-F-Phe) peptides which require peptidase cleavage to release m-F-Phe . Competition studies with a specific dipeptide detector (alanyl-alpha-thiophenylglycine) enabled us to determine Ki values of 2.6 microM for nikkomycin Z and 350 microM for polyoxin D . Rates of uptake of the peptidyl-nucleosides are approximately 30 times lower than those of the m-F-Phe peptides (apparent maximal velocities: nikkomycin Z, 62 pmol min-1 mg (dry weight) of cells-1; M-F-Phe alanine 1.3 nmol min-1 mg (dry weight) of cells-1) . For both the m-F-Phe peptides and the peptidyl-nucleosides, the affinity of the drug for the transport system is an important determinant of its whole-cell activity.

Am J Med Sci, 1985 Oct, 290(4), 135 - 42
Disseminated candidiasis: a comparison of two immunologic techniques in the diagnosis; Fisher JF et al.; Eighty-five subjects were tested for the presence of circulating candidal antigen (CAg) and anti-candidal antibody (CAb) using both an enzyme immunoassay (ELISA) and counterimmunoelectrophoresis (CIE) . The 72 studied controls included laboratory volunteers; hospitalized patients without evidence of infection; febrile hospitalized patients without evidence of candidiasis; and patients with superficial candidiasis and candiduria . The control subjects were compared with 13 patients with proven disseminated candidal infection (disease prevalence = 15%) . The ELISA CAb test was of greater individual sensitivity (92%) in separating patients with systemic candidiasis from all controls combined than the ELISA CAg, CIE CAg, or CIE CAb test (61%, 15%, 69%, respectively) . The CIE CAg test, though specific (100%), was insensitive . Sensitivity, specificity, and predictive values were generally enhanced by employing combinations of tests . Sera from patients with disseminated candidiasis were much more likely to yield a positive result by two or more serologic tests than were control sera (p = less than 0.0004) . The sensitivity of combinations ranged from 15% to 92% . The specificity of combinations ranged from 21% to 100% . The predictive value positive of combinations test ranged from 40% to 100% . Predictive value negative of combinations ranged from 69% to 98% . Patients with a variety of superficial and deep candidal infections apparently have detectable circulating CAb and/or CAg . The ELISA CAb test was superior to the other tests in identifying patients with disseminated candidiasis . Combinations of serologic tests may be superior to individual tests in the diagnosis or exclusion of serious disease due to Candida albicans.

Sabouraudia, 1985 Oct, 23(5), 389 - 93
Changes in surface topography of Candida albicans during morphogenesis; Brawner DL et al.; Temporal studies of germ-tube forming yeast cells of Candida albicans by scanning and transmission electron microscopy indicate that extensive vacuolation and possibly also cell wall changes may cause walls of the parent yeast cell to collapse during specimen preparation . This collapse does not occur in cells which have been grown in conditions that suppress germ tube formation and have undergone the same preparative treatment.

Mycopathologia, 1985 Oct, 92(1), 31 - 5
Effect of cutaneous and digestive colonization in the induction of anti-Candida albicans antibodies: experimental study; Nogueira JM et al.; Candida albicans colonization induces antibodies, which must be taken into account in the serological diagnosis of candidiasis . In order to determine the degree of this effect, an experimental study in rabbits free of specific anti-Candida antibodies by cutaneous and digestive inoculation has been carried out . The evolution of humoral response was studied over 8 weeks by indirect immunofluorescence (IIF), direct agglutination (DA), counterimmunoelectrophoresis (CIE) and double diffusion (DD) . The cutaneous colonization detectable by culture was maintained until the second week in 70% of the animals and the presence of antibodies detectable by IIF and DA was observed after the 2nd week . The highest antibody titre by IFF and DA was 1/64, and was reached in the 5th week, with a tendency to drop in the following weeks . Precipitins were only detected by CIE in 15% of the animals in the 7th week . Elimination of yeast in stools continued only in 20% of the animals in the 2nd week of the experiment . Antibodies were detected by IIF and DA after the 2nd week, with the highest titres detectable by IFF in the 5th week . Precipitant antibodies detectable by CIE appeared in 15% of the animals in the 8th week.

Mycopathologia, 1985 Oct, 92(1), 11 - 8
Cellular and humoral immune responses to Candida albicans in subcutaneously infected mice; Ponton J et al.; Pure mycelial and yeast cultures of Candida albicans were produced in a low sulphate medium . Groups of mice were injected subcutaneously with increasing doses of viable or heat-killed mycelial or yeast cells and the kinetics of delayed-type hypersensitivity (DTH), anti-mycelial and anti-yeast antibodies were studied . Both the dose and the morphological phase of C . albicans showed an influence on the development of the DTH, but the viability is the factor which showed the highest influence on this reaction, since on the one hand mice infected with viable yeast or mycelial cells developed higher DTH levels than mice injected with heat killed cells, and on the other hand this factor seems to play an important role in the kinetics of DTH response . The enzyme-linked immunosorbent assay has been adapted to detect antibodies to yeast and mycelial phase cytoplasmic antigens of C . albicans . In contrast with the DTH reactions, neither dose, morphological phase nor viability played an important role on the antibody titer developed . However, the use of mycelial cytoplasmic antigens seems to be better than the yeasts to detect anti-Candida antibodies over the last days studied.

Br J Dermatol, 1985 Oct, 113(4), 415 - 24
Contact sensitivity to Candida albicans--comparative studies in man and animal (guinea-pig); Tagami H et al.; We studied the elicitation of contact sensitivity to Candida albicans antigen in guinea-pigs with experimental cutaneous candidiasis and in humans, using commercially available potent 1:100 C . albicans antigen (Torii) by patch testing on abraded skin . In guinea-pigs, non-immune animals became patch test-reactive 4-5 days after topical application of viable C . albicans, either under occlusion or without occlusive dressings, concurrently with the demonstrability of delayed responses to intradermally injected 1:10 000 Candida antigen . In humans, all healthy adults who showed delayed hypersensitivity reactions to intradermally injected 1:10 000 C . albicans antigen demonstrated positive patch-test reactions to 1:100 C . albicans antigen . There was a significant correlation between the magnitude of responses to these tests . In contrast, no positive patch test reactions were elicited to the 1:100 C . albicans antigen on neonatal skin, emphasizing the lack of irritability of this test agent . These results also indicate that in humans contact sensitivity to Candida antigen occurs during later life because C . albicans is a ubiquitous organism . The practical value of this Candida patch test for evaluation of patients' immune function was assessed by a prospective study in patients with various skin disorders . The results obtained suggested some potential value of the test for evaluation of cell-mediated immune function of patients with regard to ubiquitous recall antigens.

Immunology, 1985 Oct, 56(2), 373 - 6
Monocyte subsets in the production of inhibitory factor by Candida albicans-activated human T cells; Lombardi G et al.; Macrophages are essential for the proliferative response of human T lymphocytes to a purified polysaccharide extract from Candida albicans (MPPS) . The role of macrophages as antigen-presenting cells in the production of an antigen non-specific inhibitory factor (nsINH) by MPPS-activated T cells was also investigated . Fc receptor positive (FcR+) or negative (FcR-) plastic-adherent mononuclear cells were used as MPPS-presenting cells, and the results show that the FcR- subset is mainly responsible for the release of nsINH from activated T cells.

Arch Ophthalmol, 1985 Oct, 103(10), 1570 - 3
The effects of subconjunctival miconazole in the treatment of experimental Candida keratitis in rabbits; Ishibashi Y et al.; Subconjunctival miconazole (1.2 mg/day for three weeks) produced a marked clinical improvement in the ocular lesions produced by inoculation with Candida albicans in a group of ten rabbits . Clinical scores of affected eyes were significantly lower in this treated group than in a control group of ten untreated rabbits . All cultures of corneal scrapings were negative on the 15th day after inoculation in the treated group, while three cultures were still positive at the end of the experiment (day 21) in the control group . Histopathologic examination showed considerably less-severe inflammatory changes in the eyes of treated animals compared with those of control animals.

Mutat Res, 1985 Oct, 152(1), 15 - 23
Transmission and expression of mutations to nalidixic acid resistance among products of protoplast fusion crosses of Candida albicans; Haught MA et al.; Earlier studies suggested that heritable resistance to nalidixic acid (Nal) induced in the asexual, pathogenic yeast Candida albicans by growth on Nal results from mitochondrial mutation . To determine conclusively whether mutations to Nal resistance are cytoplasmic or nuclear, several stable Nal-resistant (Nalr) mutants exhibiting distinctive differences in degrees of Nal resistance were obtained from each of two doubly auxotrophic strains (Ade-, Thr- and Arg-, His-), both derived from the same wild-type stock . Inheritance of Nal resistance was then assessed in a series of protoplast fusion crosses between complementing auxotrophs . The initial, intact cellular products of a fusion cross are prototrophic heterokaryons which frequently assort single parental nuclei into monokaryotic blastospores containing biparental cytoplasms . Occasional karyogamy within heterokaryons also yields prototrophic hybrid monokaryons which can undergo recombinations for chromosomal markers through spontaneous or induced mitotic crossing-over . Segregation and expression of Nal resistance among non-hybrid, parental-type monokaryons from Nalr X Nals heterokaryons showed that Nalr mutations are nuclear and that their expressions are not noticeably affected by admixture of cytoplasms of sensitive and resistant parental strains . Analyses of heterokaryons and hybrid monokaryons from Nalr X Nals and Nalr X Nalr crosses demonstrated that Nal resistance is recessive to sensitivity, and that independent Nalr mutations arise at one gene in the Ade-, Thr- strain and at a separate, complementing single gene in the Arg-, His- strain . Prior work demonstrated that induction of Nalr mutations in wild-type C . albicans depends profoundly on the (i) carbon and nitrogen, (ii) growth temperature, (iii) contact with particular metabolic inhibitors and (iv) division stage of cells during exposure to Nal . The present observations indicate that the character of cellular auxotrophies can determine the genetic loci at which Nalr mutations can be recovered.

J Infect Dis, 1985 Oct, 152(4), 710 - 5
Yeast adhesion in the pathogenesis of endocarditis due to Candida albicans: studies with adherence-negative mutants; Calderone RA et al.; Two spontaneous cerulenin-resistant mutants of Candida albicans, 4918-2 and 4918-10, were unable to adhere in vitro in fibrin-platelet clots . Because in vitro adherence correlates well with colonization of nonbacterial thrombotic endocarditis on traumatized valvular endocardium, 50% infectious dose studies were performed with a rabbit model of endocarditis . Wild-type C . albicans required 10(3.6) +/- 0.12 cfu in comparison with 10(5.73) +/- 0.31 and 10(7.3) +/- 0.21 cfu for mutants 4918-2 and 4918-10, respectively . The relative avirulence of mutant strains in producing endocarditis was not attributed to accelerated clearance of these strains from the bloodstream . In fact, clearance of wild-type and mutant strains was almost identical . In the same animals renal candidiasis was observed with all strains of C . albicans, although the number of cfu per gram of kidney was higher after infection with wild-type C . albicans . Thus, strains of C . albicans with reduced ability to adhere in vitro to a fibrin-platelet matrix are relatively avirulent in the rabbit endocarditis model.

J Bacteriol, 1985 Oct, 164(1), 7 - 13
Circular mitochondrial genome of Candida albicans contains a large inverted duplication; Wills JW et al.; The mitochondrial DNA (mtDNA) of the dimorphic fungus Candida albicans has a molecular size of 41 kilobase pairs as judged by summation of the fragment sizes produced by digestion with restriction endonucleases EcoRI, PvuII, and a combination of both enzymes . Five of the six EcoRI fragments comprising the mitochondrial genome have been cloned into the plasmid vector, pBR322 . Restriction mapping revealed a circular map as predicted by previous observations with the electron microscope . The use of nick-translated, purified mtDNA to probe digests of mtDNA from other strains of C . albicans revealed a common restriction pattern . Use of nick-translated, cloned EcoRI fragments to probe digests of mtDNA revealed a large (at least 5 kilobase pairs), inverted duplication as well as a smaller (less than 0.4 kilobase pairs) region of related sequences.

Infect Immun, 1985 Oct, 50(1), 97 - 101
Factors governing adherence of Candida species to plastic surfaces; Klotz SA et al.; The ability of Candida albicans and Candida spp . to adhere to inert polymeric surfaces may allow these organisms direct ingress into the human host . Biophysical characterization of this adherence shows that the forces responsible for such adherence are attractive London-van der Waals forces (or hydrophobic forces) and electrostatic forces . The hydrophobic affinity of yeasts was determined by (i) a water-hydrocarbon two-phase assay and by (ii) measurement of the contact angle (theta) of a liquid droplet on a monolayer of yeast cells . The hydrophobicity of the yeasts correlated with the tendency of yeasts to adhere to polystyrene and was reduced in the presence of Tween 20 . The adherence of yeasts to polymers of increasing hydrophobicity (determined by the contact angle method) was directly proportional to theta . Yeast surface charges were altered by selectively blocking amino and carboxyl groups . The more positively charged yeasts adhered in greater numbers . Increasing the molarity of NaCl increased yeast adherence . These forces probably contribute to the negative cooperativity (determined by Scatchard and Hill plot) that characterizes the adherence of yeasts to polymers.

Infect Immun, 1985 Oct, 50(1), 297 - 303
Induction of natural killer cell activity by inactivated Candida albicans in mice; Marconi P et al.; Injection of merthiolate-inactivated yeast form cells of Candida albicans into the peritoneal cavities of mice induced the appearance of a cytolytic effector population against YAC-1 tumor cell lines . This induction was maximally manifested in 5- to 8-week-old animals 3 to 4 days after injection of 2 X 10(7)C . albicans cells, and the peritoneal lytic population exerted its optimum cytotoxic effect after 4 h of incubation . No significant natural cytotoxic activity was generated by C . albicans in the bone marrow or thymus, whereas there was a slight, transient, but significant depression of natural splenic cytotoxicity . Experiments performed to characterize the natural cytotoxic population elicited by the inactivated yeast showed that the effectors were nonadherent, nonphagocytic cells . Moreover, the anti-YAC-1 lytic activity was partially sensitive to anti-Thy1.2 serum and was completely abrogated by treatment of peritoneal nonadherent cells with monoclonal anti-asialo GM1 antibodies . Finally, the peritoneal population of cytotoxic cells induced by C . albicans was fully susceptible to Ly5.1 plus anti-immunoglobulin G2a and complement lysis . Although different cell populations could be induced by inactivated C . albicans, all of our data support the view that the anti-YAC-1 activity was entirely attributable to natural killer lymphocytes.

J Gen Microbiol, 1985 Oct, 131 ( Pt 10), 2581 - 9
Effects of imidazole- and triazole-derivative antifungal compounds on the growth and morphological development of Candida albicans hyphae; Odds FC et al.; Six azole-derivative antifungal compounds affected several aspects of Candida albicans hyphal development with only a relatively small degree of inhibition of growth rate, measured in terms of ATP concentration, whereas amphotericin B and 5-fluorocytosine affected morphology only when they also substantially inhibited fungal growth rate . At 10(-8) M, all the azoles tested inhibited branch formation by C . albicans hyphae . At 10(-7) M and higher concentrations, clotrimazole and miconazole strongly suppressed emergence of new hyphal outgrowths from parent yeast cells, whereas ICI 153066 and itraconazole had little effect on this phenomenon and ketoconazole and tioconazole had intermediate effects . At the highest concentrations tested (10(-5) M) hyphal development was ultimately arrested by the azole compounds and the fungus grew predominantly in the form of budding yeast cells; however, none of the azole antifungals prevented initial emergence of an apparently normal germ tube . The antifungals only exerted their morphological effects when they were present in the culture medium: removal of the compounds after exposure of C . albicans to them led to reversion to normal growth.

Biochem J, 1985 Sep 15, 230(3), 765 - 70
Inhibition of squalene epoxidase by allylamine antimycotic compounds . A comparative study of the fungal and mammalian enzymes; Ryder NS et al.; The inhibition of squalene epoxidase by the allylamine antimycotic agents naftifine and compound SF 86-327 was investigated, with particulate enzyme preparations from the pathogenic yeasts Candida albicans and Candida parapsilosis and from rat liver . Both naftifine and compound SF 86-327 were potent inhibitors of the Candida epoxidases and showed apparently non-competitive kinetics with respect to the substrate squalene . The Ki values for naftifine and compound SF 86-327 in the C . albicans system were 1.1 microM and 0.03 microM respectively . The C . parapsilosis enzyme was slightly more sensitive to inhibition . Varying the concentrations of cofactors or the soluble cytoplasmic fraction (S200) had no effect on the inhibition . The epoxidase from rat liver was much less sensitive (Ki for compound SF 86-327 was 77 microM) . The inhibition was also qualitatively different from that in Candida, being competitive with respect to squalene and also with respect to the S200 fraction . S200 fraction derived from C . albicans also antagonized the inhibition of the epoxidase from liver, but the liver S200 fraction did not affect inhibition of the Candida enzyme by compound SF 86-327 . There was no evidence for an irreversible or mechanism-based inhibition of either the fungal or the mammalian epoxidase . The selective inhibition of squalene epoxidase was sufficient to account for the known antimycotic action of the compounds.

Mycopathologia, 1985 Sep, 91(3), 187 - 92
Pathological observations in experimental candida infection of sensitized guinea pigs; Isoda M; Guinea pigs immunized intramuscularly with heat-killed or viable Candida albicans were infected intracutaneously with C . albicans . Animals with negative delayed hypersensitivity against C . albicans antigen showed similar lesions with non-immunized controls . Delayed hypersensitivity-positive guinea pigs, which were detected in the animals immunized with heat-killed C . albicans in CFA and IFA, demonstrated a delay of the resolution of the inflammatory tissue reaction and, in the animals immunized with C . albicans in CFA, developed a granuloma . These results suggest that both humoral and cell-mediated immunities do not play a significant role for protection against candidiasis and at a late stage of infection, cell-mediated immunity may play a secondary role of the enhancement of resistance to candida infection associated with granuloma formation.

J Hand Surg {Am}, 1985 Sep, 10(5), 719 - 22
Candida albicans tenosynovitis of the hand; Yuan RT et al.; Invasive fungal infections of the hand are extremely rare and usually require an immunocompromised host . We report the first known case of Candida albicans tenosynovitis of the hand presenting as a mass in a boy with Buckley's immunodeficiency . Treatment was successful after radical synovectomy of both the flexor and extensor aspects of the hand after he failed to respond to combined amphotericin B and 5-fluorouracil therapy . Fungal tenosynovitis should be considered when swelling and decreased range of motion occur in the hands or digits of an immunocompromised host, especially if pain is not a prominent symptom.

Infect Immun, 1985 Sep, 49(3), 780 - 4
Experimental candidiasis after thermal injury; Fader RC et al.; The ability of Candida albicans to infect thermally injured mice was studied . Female mice were either left unburned or given a 20% total body surface area 2-s or 7-s scald burn . The wound or skin surface was then inoculated with a human burn wound isolate of C . albicans . At 4 h postburn, approximately 10(2) to 10(3) CFU/g of tissue could be recovered from the skin of burned and unburned animals . Unburned mice cleared the organisms from the skin by 72 h, whereas in 7-s-burned animals, the candida increased in numbers to approximately 10(7) CFU/g of tissue . The ability of the organisms to invade systemically after wound surface inoculation was examined in mice given either a 2-s or a 7-s scald burn . Each injury was histologically confirmed as a full-thickness (third degree) burn, with slightly deeper tissue damage observed with the 7-s burn . At each time period examined (1, 4, 7, and 10 days), there were significantly fewer organisms in the wounds of mice given the 2-s injury than in wounds of mice burned for 7 s (P less than 0.05) . In 3 of 33 mice given a 7-s injury, organisms were recovered from the kidneys at the time of sacrifice, whereas no evidence of invasion into the kidneys was noted in mice given a 2-s thermal injury . This study demonstrated that thermal injury enhances the ability of C . albicans to infect mice and that the depth of burn appears to be an important factor in determining whether the organisms can invade the burn wound to cause systemic infection . This animal model should be valuable in elucidating the virulence factors of C . albicans that play a role in the pathogenesis of candidiasis after thermal injury.

Infect Immun, 1985 Sep, 49(3), 724 - 30
Recombinant and natural gamma-interferon activation of macrophages in vitro: different dose requirements for induction of killing activity against phagocytizable and nonphagocytizable fungi; Brummer E et al.; Recombinant murine gamma-interferon (IFN) and supernatants from concanavalin A (ConA)-stimulated spleen cells were tested for their ability to activate resident peritoneal macrophages (M phi) for fungicidal activity . M phi monolayers pulsed overnight with IFN exhibited significantly enhanced fungicidal activity against Candida albicans (44 +/- 12 versus 0.0%) and Blastomyces dermatitidis (34 +/- 1 versus 3 +/- 3%) . The effect of IFN was dose dependent; however, less IFN (10 U/ml) was required to activate M phi to kill phagocytizable C . albicans than to kill nonphagocytizable B . dermatitidis (1,000 U/ml) . ConA-stimulated spleen cell supernatants were also able to activate M phi for fungicidal activity against both fungi . The capacity of ConA-stimulated spleen cell supernatants to activate M phi for fungicidal activity was neutralized in the presence of antibody to murine IFN . ConA-treated monolayers acquired the ability to kill C . albicans, but not B . dermatitidis, which was shown to be associated with residual (10%) lymphocytes in the monolayers . Lipopolysaccharide (0.001 to 10 micrograms/ml) failed to consistently activate M phi for fungicidal activity . These data show that IFN can exert an immunoregulatory role on M phi defense against these fungal pathogens.

Ann Inst Pasteur Microbiol, 1985 Sep-Oct, 136B(2), 181 - 93
{Changes in the cell wall of Candida albicans cultivated in the presence of sublethal doses of nystatin}; Bonaly R et al.; Subinhibitory doses of nystatin in the culture medium of Candida albicans gave yeasts with altered cell walls . Major alterations chiefly concerned the antigenic peptidomannans . Their amount in wall and their molecular weight were smaller in yeast grown with nystatin than in normal cultured yeast . Glucans and chitin were not seriously modified . Polymers requiring lipidic intermediates such as dolichol phosphate for their biosynthesis seemed to be most affected by the presence of nystatin.

J Biol Buccale, 1985 Sep, 13(3), 227 - 36
Cultivable microflora of plaque from full denture bases and adjacent palatal mucosa; Gusberti FA et al.; Anaerobic cultural techniques and rapid biochemical identification tests normally employed for periodontal plaque were utilized for the analysis of plaque samples taken from denture bases and corresponding adjacent mucosa . Results were compared with those or more comprehensive microbiological investigations . Forty four samples were obtained from the denture bases and adjacent palatal mucosa of 12 patients wearing full upper dentures . The specimens were then collected in Reduced Transport Fluid and processed in the anaerobic glove box . Samples were plated on Enriched Trypticase Soy Agar (ETSA) and cultured under both aerobic and anaerobic conditions . In addition plaque samples were plated on Sabouraud medium . Facultative bacteria predominated in both denture and palatal plaques . Significantly greater numbers of cocci were recovered in the samples from palatal mucosa . More rods were found in denture plaque . Anaerobes were present in both instances . Among the anaerobes, saccharolytic Bacteroides were identified with the highest frequency, while Veillonella species were present in the greatest quantity . Recovery of yeasts was similar for both ETSA and Sabouraud media incubated aerobically . As has been found in other microbiological studies Candida albicans represented only a minor part of the total cultivable flora.

J Gen Microbiol, 1985 Sep, 131 ( Pt 9), 2367 - 75
The involvement of cell wall expansion in the two modes of mycelium formation of Candida albicans; Soll DR et al.; When budding cells of Candida albicans are starved for 20 min and then diluted into fresh nutrient medium at 37 degrees C, pH 6.7, they form mycelia by two alternative modes . For cells with small buds, the bud expands apically, resulting in a transiently tapered daughter cell . With continued growth, the daughter cell tapers into an elongated mycelium . For cells with large buds, the bud completes expansion in the budding form, the mother cell and then the daughter bud evaginate, and the evaginations grow as mycelia . The present study investigates whether the temporal and spatial changes in the zones of wall expansion during bud growth are involved in the two modes of mycelium formation . Data are presented which demonstrate that the transition circumference which determines the two modes of mycelium formation and the transition circumference at which the active apical expansion zone shuts down are both 7 micron . This exact correlation suggests that starved cells with buds with a circumference of less than 7 micron form mycelia in the tapering mode due to the reactivation of the still present apical expansion zone, and that starved cells with buds with a circumference greater than 7 micron complete bud growth by general expansion due to the absence of the apical expansion zone at the time of starvation.

J Gen Microbiol, 1985 Sep, 131 ( Pt 9), 2209 - 16
Dimorphism in Candida albicans: contribution of mannoproteins to the architecture of yeast and mycelial cell walls; Elorza MV et al.; Wall mannoproteins of the two (yeast and mycelial) cellular forms of Candida albicans were solubilized by different agents . Boiling in 2% (w/v) SDS was the best method, as more than 70% of the total mannoprotein was extracted . Over 40 different bands (from 15 to 80 kDal) were detected on SDS-polyacrylamide gel electrophoresis of this material . The residual wall mannoproteins were released after enzymic (Zymolyase and endogenous wall beta-glucanases) degradation of wall glucan, suggesting that they are covalently linked to this structural polymer . Four bands (of 160 kDal, 205 kDal and higher molecular mass) were observed in the material released from yeast walls but only the two smaller components were detected in the material obtained from mycelial walls . Moreover, the mannoproteins of high molecular mass, which are covalently linked in walls of normal cells, were not incorporated into walls of regenerating protoplasts, but non-covalently linked mannoproteins were retained from the beginning of the process.

Ann Clin Lab Sci, 1985 Sep-Oct, 15(5), 406 - 13
Specificity and mechanism of in vitro adherence of Candida albicans; Reinhart H et al.; Adherence of 14C-glucose labeled Candida albicans to vaginal epithelial cells was measured in the presence of 10 potential inhibitory sugars at concentrations of 5 to 150 mg per ml for 90 minutes at 37 degrees C . In competitive inhibition experiments, no inhibition of adherence was seen with any sugar at any concentration . On the contrary, with the exception of the aminosugars glucosamine, galactosamine, and mannosamine, increased attachment of Candida to vaginal epithelial cells was found in the presence of dextrose, galactose, mannose, alpha-methyl-mannoside, N-acetyl-glucosamine, N-acetyl-galactosamine, and N-acetyl-mannosamine . Increased adherence was not associated with recognizable changes in the electron microscopic appearance of Candida cell surface or alterations in fungal cell hydrophobicity as measured by interaction chromatography . Measurement of nonreceptor-specific adherence of Candida to glass beads revealed similar increased attachment in the presence of the test sugars, suggesting that adherence of Candida may not require specific yeast adhesin-cell receptor interaction.

Mycopathologia, 1985 Sep, 91(3), 175 - 9
Use of killer toxins for computer-aided differentiation of Candida albicans strains; Polonelli L et al.; Killer toxins were isolated from eight selected killer yeasts . Their activity on 100 Candida albicans isolates of human and animal origin was studied . A computer aided system for differentiating C . albicans strains was developed . By using this system, it was possible to differentiate 14 biotypes of C . albicans isolates based on their susceptibility to the killer toxins.

Mycopathologia, 1985 Sep, 91(3), 165 - 70
Secretory IgA and secretory component in women affected by recidivant vaginal candidiasis; Romero-Piffiguer MD et al.; Local immunity was evaluated in 47 patients affected by recidivant vaginal candidiasis and 33 control women . IgG, IgA, IgM and secretory component (SC) were determined by single radial immunodiffusion in samples of cervicovaginal secretion . IgG in dosable levels was detected in 17/47 samples (36.2%) and IgA in 15/47 patients (31.9%) whereas in the controls, the incidence was 31/33 (93.9%) for IgG and 24/33 (72.7%) for IgA . The difference was significative (P less than 0.001) for both immunoglobulins . Significant differences were not obtained for IgM . The SC was detected in 4/47 cervicovaginal secretions of patients affected by candidiasis (8.5%) whereas in the control samples the incidence was 21/33 (63.6%) (P less than 0.001) . In only 2/15 patients with dosable levels of IgA (13%) the secretory nature of this immunoglobulin could be shown by its reaction with anti-SC serum . In the control group, secretory IgA was detected in 19/24 cases (79%) (P less than 0.001) . Serum immunoglobulins levels were normal . The lack of secretory IgA and SC in the secretion could be related to the adherence capacity of the Candida albicans to epithelial cells.

J Antimicrob Chemother, 1985 Sep, 16(3), 397 - 9
Influence of growth phase on the susceptibility of Candida albicans to butoconazole, oxiconazole, and sulconazole; Beggs WH; Three topical antifungal imidazoles were examined for fungicidal potential . At 8 X 10(-5) M, butoconazole, oxiconazole, and sulconazole were strictly fungistatic against early stationary phase Candida albicans cells diluted into fresh medium . With early logarithmic phase organisms, oxiconazole again was fungistatic, but sulconazole and butoconazole were highly lethal at only 2 X 10(-5) M.

Exp Hematol, 1985 Sep, 13(8), 791 - 5
Treatment of systemic candidiasis in neutropenic dogs with ketoconazole; Weber MJ et al.; The present study evaluated the activity of ketoconazole in neutropenic dogs with systemic candidiasis . Five dog pairs were made neutropenic by intravenous cyclophosphamide (50 mg/kg) and challenged with either 10(6) or 10(7) colony-forming units (CFU) of Candida albicans . Half of the dogs received ketoconazole (10 mg/kg) daily beginning 24 h after challenge . All were killed at 96 h and liver, spleen, and kidney were cultured . Of four dogs given 10(6) CFU, two untreated dogs had 9 X 10(3) to 1 X 10(5) CFU/g wet tissue, compared to 0 CFU in ketoconazole-treated dogs . With inoculum increased to 10(7) CFU, three untreated dogs had 2 X 10(4) to 3 X 10(5) CFU/g wet tissue, while three ketoconazole dogs had 0-5 X 10(3) CFU/g wet tissue . The effect of ketoconazole on autologous marrow reconstitution in dogs with systemic candidiasis was examined by infusing autologous cryopreserved marrow into four dogs one day after lethal whole body irradiation (800 rad) . Once neutropenic, they were challenged with 10(7) CFU of C . albicans . Two dogs received no ketoconazole and died of disseminated candidiasis, without marrow reconstitution . Two dogs received ketoconazole for 25 days . Prompt marrow recovery occurred and they remained healthy . There was no evidence of infection at death . These studies quantitatively demonstrate the in vivo effectiveness of ketoconazole in reducing tissue infection with C . albicans in neutropenic dogs . They provide in vivo evidence that ketoconazole can prevent or cure systemic candidiasis in the bone marrow transplant setting without significant inhibition of marrow recovery.

J Infect Dis, 1985 Sep, 152(3), 577 - 91
Cutaneous, ocular, and osteoarticular candidiasis in heroin addicts: new clinical and therapeutic aspects in 38 patients; Dupont B et al.; Of 38 heroin addicts treated for systemic candidal infections, 36 had metastatic cutaneous lesions (deep-seated scalp nodules and pustulosis in hairy zones), 15 had ocular localizations (mainly chorioretinitis), and 10 had osteoarticular involvement (vertebrae, costal cartilage, knees, and sacroiliac) . Such cutaneous lesions have not previously been described in classical systemic candidiasis; we also observed hair invasion by candidal hyphae . Candida albicans was the exclusive species isolated, in contrast to other visceral candidiases in heroin addicts . All isolates were sensitive to amphotericin B, flucytosine, and ketoconazole . Thirty-one visceral localizations were treated only with ketoconazole . Results were favorable in 15 of 18 cutaneous, 6 of 6 ocular, and 4 of 7 osteoarticular cases of involvement . This outbreak coincided with introduction of a new heroin on the drug market in the Paris area . C . albicans was not isolated from the drug . Pathogenesis of this syndrome is unclear.

Infect Immun, 1985 Sep, 49(3), 654 - 63
Ecology of Candida albicans gut colonization: inhibition of Candida adhesion, colonization, and dissemination from the gastrointestinal tract by bacterial antagonism; Kennedy MJ et al.; Antibiotic-treated and untreated Syrian hamsters were inoculated intragastrically with Candida albicans to determine whether C . albicans could opportunistically colonize the gastrointestinal tract and disseminate to visceral organs . Antibiotic treatment decreased the total population levels of the indigenous bacterial flora and predisposed hamsters to gastrointestinal overgrowth and subsequent systemic dissemination by C . albicans in 86% of the animals . Both control hamsters not given antibiotics and antibiotic-treated animals reconventionalized with an indigenous microflora showed significantly lower gut populations of C . albicans, and C . albicans organisms were cultured from the visceral organs of 0 and 10% of the animals, respectively . Conversely, non-antibiotic-treated hamsters inoculated repeatedly with C . albicans had high numbers of C . albicans in the gut, and viable C . albicans was recovered from the visceral organs of 53% of the animals . Examination of the mucosal surfaces from test and control animals indicated further that animals which contained a complex indigenous microflora had significantly lower numbers of C . albicans associated with their gut walls than did antibiotic-treated animals . The ability of C . albicans to associate with intestinal mucosal surfaces also was tested by an in vitro adhesion assay . The results indicate that the indigenous microflora reduced the mucosal association of C . albicans by forming a dense layer of bacteria in the mucus gel, out-competing yeast cells for adhesion sites, and producing inhibitor substances (possibly volatile fatty acids, secondary bile acids, or both) that reduced C . albicans adhesion . It is suggested, therefore, that the indigenous intestinal microflora suppresses C . albicans colonization and dissemination from the gut by inhibiting Candida-mucosal association and reducing C . albicans population levels in the gut.

Infect Immun, 1985 Sep, 49(3), 609 - 14
Enzymatic release of germ tube-specific antigens from cell walls of Candida albicans; Sundstrom PM et al.; The differences between blastospores and germ tubes of Candida albicans, as previously shown by immunofluorescence, were further studied by comparing digests of cell walls of both growth forms . Organisms were surface labeled with 125I, and cell walls were digested enzymatically . When Zymolase digests were treated with polyclonal, polyspecific antiserum to C . albicans 441B, which stains only germ tubes in immunofluorescence assays, components of molecular weights 200,000 and 155,000 were immunoprecipitated from digests of germ tubes of strain B311, but nothing was recovered from blastospores . Whereas the 200,000-molecular-weight component was found in the three strains tested, the 155,000-molecular-weight component was found only in strain B311 . When Zymolase digests were treated with unadsorbed antiserum, which stains both blastospores and germ tubes in immunofluorescence assays, an additional component was precipitated from digests of both growth forms with a molecular weight greater than the 200,000-molecular-weight marker . All three antigens were mannoproteins, as was shown by their abilities to bind concanavalin A and to be labeled by 125I . Also, all antigens were located on the cell surface, as was shown by the following criteria: adsorption of antisera with live organisms removed antibody to these components, and antibody eluted from surfaces of whole organisms precipitated all components . Components common to both growth forms, as well as germ tube-specific components, were detected in trypsin and chymotrypsin digests, but their molecular weights differed from those of Zymolase digests . Thus, germ tube-specific surface determinants as well as determinants common to both growth forms were detected on enzymatically released cell wall components.

Infect Immun, 1985 Sep, 49(3), 571 - 5
Genetic evidence for role of extracellular proteinase in virulence of Candida albicans; Kwon-Chung KJ et al.; The relationship between extracellular proteinase and the virulence for mice in Candida albicans was studied by using a set of three isolates . The set included a proteinase-producing parent (C9), a proteinase-deficient mutant derived from C9 by nitrous acid treatment (C9M1), and a spontaneous revertant (C9M1M) obtained by mouse passage of C9M1 . The morphological markers and the carbon assimilation pattern were identical in these isolates . Isolate C9 produced a high level of proteinase in vitro and caused fatal infection (100%) within 21 days . The mutant produced no detectable enzymes in vitro, and all mice survived until day 22 . Only 30% of the mice infected with C9M1 died between day 23 and 30 . The isolates recovered from the dead mice were found to be proteinase sufficient, indicating that the mice died after the organism in tissue had reverted . The C9M1M isolate produced proteinase in vitro at 44% the level of C9 and induced fatal infection in 90% of the mice within 30 days . The number of CFU recovered from the kidneys correlated with the level of proteinase produced in vitro and, in turn, the rate of fatal infection produced by the isolates . These results support a previous observation indicating that proteinase activity is one of the virulence factors associated with C . albicans.

J Antibiot (Tokyo), 1985 Sep, 38(9), 1182 - 203
Structure activity relationships of synthetic antibiotic analogues of chryscandin; Komori T et al.; Anti-yeast activity with a series of chryscandin derivatives showed that the O-methyl-L-tyrosyl moiety is not always required for activity at the target site . On the other hand, the adenyl-3'-aminoribofuranuronic acid moiety seems to be essential for biological activity . Therefore, the various acyl derivatives on the amino group of the sugar part of the nucleoside were synthesized . 1-(6-Amino-9H-purin-9-yl)-3-(S-benzyl-L-cysteinylamino)- 1,3-dideoxy-beta-D-ribofuranuronic acid (16) showed the highest efficacy among them against Candida albicans . It exhibited sixteen-fold enhanced activity in vitro compared with that of native chryscandin . The in vivo activity of 16 against experimental infection of C . albicans showed the almost same as that of 5-fluorocytosine and a superior to that of ketoconazole.

Microbiologia, 1985 Sep, 1(1-2), 5 - 17
Preliminary characterization of two glucan synthetase preparations and their reaction products from Candida albicans; Andaluz E et al.; Two glucan synthetase preparations from Candida albicans were obtained by lysis of regenerating protoplasts (enzyme A) or mechanical breakage of yeast cells (enzyme B) . Enzyme A was insensitive to EDTA or GTP but it was stimulated by a combination of both agents . Enzyme B was inhibited by EDTA, this inhibition being released by increasing the concentration of the chelating agent or by addition of GTP to the assay mixtures . Enzyme A was further activated by glycerol and sodium fluoride . The reaction products were characterized as linear beta-1,3-linked glucans on the basis of their resistance to periodate and susceptibility to beta-glucanases . In both cases the "in vitro" synthesized radioactive chains were added to the non-reducing end of cold, performed glucan or to and acceptor other than glucan . At least, part of the preformerd glucan chains of enzyme A, but no those of enzyme B, showed a free reducing terminal . On the basis of the origin of both enzyme preparations it is suggested that glucan molecules are synthesized while bound to an acceptor of a different nature which is subsequently excised.

Diagn Microbiol Infect Dis, 1985 Sep, 3(5), 419 - 32
Serologic analysis of antigen-specific reactivity in patients with systemic candidiasis; Au-Young JK et al.; Antibody responses to candidal polypeptides and mannans were studied in patients with systemic candidiasis, candiduria, and other fungal and bacterial infections, and in healthy laboratory personnel to determine the diagnostic value of these immunologic responses . When tested by immunoblot analysis, sera from 15 patients with systemic candidiasis frequently contained antibodies to three antigens: 15 of 15 sera from patients with invasive disease reacted to a molecular species having a molecular weight (Mr of 90-200 kd, 13 of 15 reacted with a 45-kd polypeptide, and 12 of 15 reacted with a 17-kd polypeptide . Lesser reactivity was observed in 11 of 15 sera with a 28-kd candidal antigen and in 9 of 15 to a 57-kd candidal antigen . Quantitation of antibody titers against the 45-kd candidal polypeptide demonstrated much higher immunoreactivity in patients with systemic candidiasis than in patients with superficial candidal infections, bacterial infections, other systemic mycoses, and healthy individuals . Antimannan antibody titers were measured by an enzyme-linked immunosorbent assay (ELISA) and these titers were also higher in patients with systemic candidiasis than in patients in the other categories . These differences, however, were less than those observed with the anti-45-kd polypeptide antibody . Therefore, the ability to detect systemic candidiasis is improved by testing sera for immunoreactivity to polypeptide and to mannan antigens from Candida albicans . Detection of polypeptide antibodies improves the serodiagnosis of systemic candidiasis.

Biochim Biophys Acta, 1985 Aug 16, 841(2), 215 - 22
Effect of papulacandin B and calcofluor white on the incorporation of mannoproteins in the wall of Candida albicans blastospores; Murgui A et al.; Incorporation of mannoproteins into the walls of Candida albicans blastospores (yeast phase) was followed by continuous labelling and pulse-chase experiments . The effect in the process of compounds that interfere with synthesis (papulacandin B) or assembly (calcofluor white) of structural polymers was also assessed . Mannoproteins which are kept in place by non-covalent bonds (mainly hydrogen bonds) were incorporated rapidly after their release into the periplasmic space, this process being blocked by calcofluor white . The stain had no effect on the incorporation of covalently linked mannoproteins . Papulacandin B inhibited formation of beta-glucans and incorporation of covalently linked mannoprotein molecules, whereas incorporation of hydrogen-bonded species took place normally . The results suggest that the formation of the non-covalent bonds between the mannoproteins occurs once they are secreted into the periplasmic space, whereas the formation of covalent connections between mannoproteins and wall glucan takes place at the level of the plasma membrane.

J Am Acad Dermatol, 1985 Aug, 13(2 Pt 2), 337 - 42
Chédiak-Higashi syndrome in a Venezuelan black child; Leal I et al.; One case of Chediak-Higashi syndrome (CHS) in a black male child, born to a consanguineous couple from a rural village in the State of Falcon, is described . At birth the child had marked skin depigmentation and ash-gray hair . A few months later he developed an almost normal black skin color . The diagnosis of CHS was established by the presence of large peroxidase-positive granules in his leukocytes . Neutrophils showed decreased chemotaxis and lack of digestive capacity against Candida albicans . Unusual features included extreme rarity of CHS in blacks, progressive repigmentation of the skin, and an early benign evolution . A high consanguinity index in the village from which this patient originated raised the possibility of the presence of a new cluster of this disease in Venezuela.

Am J Clin Nutr, 1985 Aug, 42(2), 252 - 62
Studies of marginal zinc deprivation in rhesus monkeys: VI . Influence on the immunohematology of infants in the first year; Haynes DC et al.; Rhesus monkey infants fed a marginally zinc-deficient diet (4 ppm) from conception through 12 mo of postnatal life were monitored for changes in hematological, biochemical, and immunological parameters . These zinc-deprived (ZD) infants were compared to control infants whose mothers were fed a zinc-replete (100 ppm) diet either ad libitum (AL) or pair-fed (PF) throughout gestation and lactation . Blast transformation of peripheral blood lymphocytes to phytohemagglutinin (PHA-P), concanavalin A (Con A), and pokeweed mitogen (PWM), was dramatically depressed in the zinc-deficient (ZD) group . Similarly, ZD infants had reduced polymorphonuclear leukocyte function as measured by chemotaxis to endotoxin-activated plasma and phagocytosis of Candida albicans . Levels of serum IgM were significantly altered in zinc-deficient infants compared to controls . Serum concentrations of IgG and IgA were similar in zinc-deficient and control infants . ZD infants also manifested a hypochromic microcytic anemia at one month of age, reduced activity of the zinc metalloenzyme alkaline phosphatase, and lower activity of SGPT.

Microbiol Sci, 1985 Aug, 2(8), 243 - 7
Adhesion of pathogenic Candida species to host surfaces; Douglas LJ; Candida infections are becoming increasingly important in compromised hosts . The pathogenic Candida species vary in their ability to adhere to mucosal and other surfaces and there is a clear correlation between adhesion and virulence . Adhesion mechanisms of the most pathogenic species, Candida albicans, are being studied in detail.

Can J Microbiol, 1985 Aug, 31(8), 696 - 701
Morphological studies of N-acetylglucosamine induced germ tube formation by Candida albicans; Hubbard MJ et al.; In N-acetylglucosamine induced germ tube formation by Candida albicans, multiple (up to five) protuberances appeared within 90 min at 37 degrees C on each yeast cell . The protuberances were extensions of the cytosol and contained vesiclelike structures . Usually only one protuberance subsequently developed into a germ tube . The germ tubes emanated from all aspects of the cell surface but seldom from the budding (long axis) poles . Pseudohyphae, which originated from the budding pole, exhibited a marked constriction at the site of emergence and were 0.6-2.5 microns in diameter compared with a diameter of 0.6-0.8 micron for germ tubes . The presence of septa confirmed that germ tubes are precursors of septate mycelia . Ultrathin-section transmission electron microscopy of aldehyde plus osmium fixed cells revealed electron-lucent walls with a thin electron-dense outer layer . A fibrillar border was also routinely associated with germ tubes . Poststaining with potassium permanganate revealed, in addition, a previously invisible fuzzy layer on the outer region of the cell wall which extended over bud scars and germ tubes and which coalesced at sites of contact between cells.

J Antimicrob Chemother, 1985 Aug, 16(2), 169 - 77
A comparison of the activity of mepartricin and amphotericin B against yeasts; Petrou MA et al.; An in-vitro comparison was made of the activity of mepartricin and amphotericin B against yeasts both in the presence and absence of pooled human plasma . The methods used included minimum inhibitory concentrations (MICs), liquid cultures and scanning electron microscopy (SEM) . Mepartricin was found to be consistently more active than amphotericin B and to exhibit a partial inhibitory action over a wider range of concentrations below the MIC . In the presence of plasma, amphotericin B had increased activity but there was a slight reduction for mepartricin . By electron microscopy both drugs exhibited a rapid effect on Candida albicans and the cell membrane was found to be their primary target . Mepartricin was found to have the additional effect of causing a delayed separation of dividing cells and damage on both sides of the septum between mother and daughter cells . This suggests interference with the enzymatic mechanism of septum formation or chitin synthesis.

J Gen Microbiol, 1985 Aug, 131 ( Pt 8), 2107 - 13
Genetic analysis of Candida albicans morphological mutants; Pomes R et al.; In contrast to some other strains, Candida albicans 1001 gave rise, upon UV irradiation, to mutants displaying a 'rough colony' morphology associated with a permanent alteration in morphogenesis which determined growth of the cells mostly as pseudohyphae . One of these mutants, C . albicans 1001FR, could form sectored (rough/smooth) colonies spontaneously, and with increasing frequency by treatment with mild UV doses (32-64 microJ mm-2) . Rough sectors corresponded to stable 'rough-filamentous' strains which never segregated smooth strains . On the other hand, smooth sectors consisted mainly of yeast cells which could occasionally revert to a rough-filamentous phenotype . We suggest that C . albicans 1001 is heterozygous for some gene involved in the control of morphogenesis, and that the described mutants should be of help in the characterization of the genetic control of dimorphism in C . albicans.

J Gen Microbiol, 1985 Aug, 131 ( Pt 8), 1853 - 61
Effect of tunicamycin on germ tube and yeast bud formation in Candida albicans; Chaffin WL; Tunicamycin is an antimicrobial agent which inhibits the first reaction of the dolichol pathway leading to N-glycosylation of proteins . The effect of tunicamycin on the growth of the dimorphic fungus Candida albicans differed depending on the growth phase of the organism . Addition of tunicamycin to stationary phase yeast cells inhibited the resumption of growth of those cells in either morphology, as cultures failed to initiate either yeast bud or germ tube formation . When tunicamycin was added to growing cells, growth was inhibited but not immediately . When it was added to germ tube cultures, nuclear division and septum formation continued for some time before ceasing . Addition of the drug to exponential phase yeast cultures resulted in an approximately 45% increase in cell number before cell division ceased and yeast accumulated in both budded and unbudded stages of the cell cycle . Accumulation of trichloroacetic acid precipitable radiolabelled protein and nucleic acid continued unchanged for some time following addition of tunicamycin; however, after a while a reduced rate of accumulation was noted.

Sabouraudia, 1985 Aug, 23(4), 313 - 5
Growth of Candida albicans in dexamethasone-supplemented media; Ghannoum M et al.; Candida albicans grown in dexamethasone (DXM) shows an apparent increase in dry weight . This increase, however, represents an artefact due to entrapment and incorporation of DXM by the yeast . Thus opportunistic infections by C . albicans which are promoted by DXM must be due entirely to effects other than growth enhancement of the organism.

Sabouraudia, 1985 Aug, 23(4), 275 - 85
Protection against systemic infections with various Candida species elicited by vaccination with Candida albicans ribosomes; Segal E et al.; This study investigated whether subcutaneous vaccination of mice with ribosomes from Candida albicans strain CBS 562 would also provide protection against infections by other isolates of Candida . Experiments with a total of 628 mice demonstrated that vaccination induced significant protection against heterologous C . albicans (serotypes A and B) and C . tropicalis isolates in terms of their 30 day survival rates . In all instances, however, protection was lower than that obtained against the homologous strain . In addition, a significant decrease in fungal colonization of the kidneys was found in immunized animals as compared to the non immunized controls . Cell-mediated immune responses against cytoplasmic extracts of the various fungi, as detected in vivo by the foot pad swelling test and in vitro by the lymphocyte transformation assay, were induced by the C . albicans ribosomal vaccination . The results show it is possible to induce cross protection to various Candida species by immunization with C . albicans ribosomes.

Sabouraudia, 1985 Aug, 23(4), 265 - 73
Effect of various antibiotics on gastrointestinal colonization and dissemination by Candida albicans; Kennedy MJ et al.; Mice were treated orally with various antibiotics to determine which members of the indigenous intestinal microflora normally suppress Candida albicans colonization and dissemination from the gastrointestinal (GI) tract . The mice were given penicillin, clindamycin, vancomycin, erythromycin, or gentamicin for 3 days, and then challenged orally with C . albicans . Penicillin, clindamycin, and vancomycin, but not gentamicin or erythromycin, decreased the total anaerobic bacterial populations in the animals ceca, and increased the enteric bacilli population levels . All three of the former antibiotics allowed C . albicans to proliferate in the gut and, subsequently, disseminate from the GI tract to visceral organs . The ability of C . albicans to associate with intestinal mucosal surfaces was also tested . It was found that antibiotics which reduced anaerobic population levels, but not enteric bacilli or aerobes, also predisposed animals to mucosal association by C . albicans . It is suggested that the strictly anaerobic bacterial populations which predominate in the gut ecosystem are responsible for the inhibition of C . albicans adhesion, colonization and dissemination from the GI tract.

Mycopathologia, 1985 Aug, 91(2), 79 - 85
Role of antibodies and effect of BCG vaccination in experimental candidiasis in mice; Maiti PK et al.; The role of humoral antibodies and the effect of BCG vaccination were studied in the experimental candidiasis in mice . The antibody suppressed, B-cell deficient animals were prepared by repeated administration of rabbit anti-mouse-mu-antiserum to the new born mice from birth onwards . Such immunodeficient animals along with controls were infected intravenously with Candida albicans, to study the course of candidal infection . It was observed that B-cell-deficient animals were found to be more susceptible to candidal infection than the controls, as indicated by their steady loss of body weight, longer mean time to death and higher viable counts of candidal cells in different organs . The anti-candidal antibodies were absent in all B-cell-deficient animals but present in the controls . These results suggest that antibodies make a contribution in protection against candidal infection in mice . The BCG vaccinated animals were prepared by repeated intravenous administration of BCG to mice and these vaccinated animals along with unvaccinated controls were challenged intravenously with C . albicans, to study the course of candidal infection . It was observed that BCG vaccination prolonged meantime to death and reduced the number of candidal cells in their kidneys.

Eur J Obstet Gynecol Reprod Biol, 1985 Aug, 20(2), 113 - 9
The influence of antibiotics on the growth of Candida albicans in the vagina: an experiment with vaginal fluid; Bisschop MP et al.; The growth of Candida albicans in fluid aspirated from the vagina of 18 women was studied . The growth of C . albicans in the aspirated vaginal fluid to which antibiotics were added proved to be enhanced in 16 out of 18 samples . The growth of C . albicans in Sabouraud medium proved not to be enhanced by the addition of antibiotics . Dilution of the Sabouraud broth and the reduction of the amount of added antibiotics did not change the outcome . It is concluded that enhancement of the growth of C . albicans in the vagina is not due to a direct growth-promoting effect of the antibiotics on the yeast . It is concluded that most probably the growth-promoting effect of antibiotics is obtained by way of an eradication of the bacterial flora harboured in the vagina.

Eur J Obstet Gynecol Reprod Biol, 1985 Aug, 20(2), 107 - 12
The growth-promoting activity of vaginal fluid for Candida albicans (and the problem of enhanced susceptibility to vaginal candidosis); Bisschop MP et al.; Fluid aspirated from the vagina of pregnant or non-pregnant women, either normally menstruating or using hormonal contraceptives, proved to be an adequate culture medium for Candida albicans . The growth-promoting activity did not differ between groups . A medical history of vaginal candidosis did not influence this growth-promoting activity . It is concluded that an enhanced susceptibility to this manifestation with C . albicans is not related to this capacity of the fluid contained in the vaginal cavity to serve as a growth-promoting medium.

Curr Eye Res, 1985 Aug, 4(8), 851 - 6
Adherence of Candida to corneal surface; Rao NA et al.; In the pathogenesis of mycotic infections, adherence of the microbes to surface structures prior to invasion appears to be the initial and essential step in a susceptible host . Adherence and inhibition of adherence of Candida albicans to rabbit corneal surface was investigated in vitro by light and scanning electron microscopic examinations . The results indicate that blastospores of Candida albicans rarely bind to intact corneal epithelium, but consistently adhere to stroma denuded of epithelium . Such adherence was inhibited by concanavalin A . With its strong affinity for the yeast cell wall carbohydrate mannan, concanavalin A may block the site of attachment of yeast cells to the corneal surface.

Am J Obstet Gynecol, 1985 Aug 1, 152(7 Pt 2), 939 - 44
Mode of action of clotrimazole: implications for therapy; Haller I; Ergosterol is an essential constituent of the fungal cytoplasmic membrane . Clotrimazole and other azoles interfere with the ergosterol biosynthesis in a concentration-dependent fashion . Although low concentrations exhibit only a partially inhibitory effect, high concentrations may completely block ergosterol synthesis . Reduction of fungal growth and inhibition of growth and fungicidal action during prolonged incubation are the corresponding effects at the cellular level that are a consequence of ergosterol depletion . The inoculum effect, the influence of the incubation period, and the influence of nutrient media, three factors that often complicate susceptibility testing in vitro, can also be explained by the mode of action of azole compounds . Another interesting characteristic of azole antifungals was revealed by the observation that hyphae and pseudomycelia of Candida albicans are much more susceptible to azoles than are yeast cells . Even 1% of the minimum inhibitory concentration of clotrimazole may totally inhibit mycelial growth in vitro . This may be of clinical importance, since germination was reported to enhance adherence of C . albicans to buccal and vaginal epithelial cells.

Obstet Gynecol, 1985 Aug, 66(2), 248 - 54
Recurrent and persistent vulvovaginal candidiasis: treatment with ketoconazole; Eschenbach DA et al.; Forty-two women were administered ketoconazole, an orally absorbed antifungal agent . The symptoms of vulvar pruritus, burning, pain, and dysuria and the signs of vulvar erythema and fissures and vaginal erythema were associated with Candida albicans . Although ketoconazole relieved symptoms and signs seven days after therapy, a high recurrence rate occurred by 28 days after therapy.

J Med Microbiol, 1985 Aug, 20(1), 97 - 104
Effect of chlorhexidine gluconate on the adherence of Candida species to denture acrylic; McCourtie J et al.; The effect of pretreatment of denture acrylic with chlorhexidine gluconate on the subsequent adherence of Candida albicans GDH 2346 was measured in vitro . Adherence was significantly reduced by pretreatment with chlorhexidine; maximal inhibition was achieved by incubation at room temperature for 30 min in 2% chlorhexidine . Inhibition of adherence was greatest when the organisms were grown in conditions that enhanced adherence the most, i.e., growth to stationary phase in high concentrations of galactose and sucrose . Yeasts grown in high concentrations of galactose, which were the most adherent to acrylic, were also the most sensitive to the fungicidal action of chlorhexidine gluconate, whereas those grown in a low concentration of glucose were the least adherent and also the most resistant . Adherence to acrylic of seven strains of C . albicans isolated from active infections (I strains) and grown in medium containing 500 mM sucrose was significantly higher than that of four strains obtained from asymptomatic carriers (C strains) . A spectrum of adherence values was obtained when various yeasts other than C . albicans were tested.

Infect Immun, 1985 Aug, 49(2), 396 - 401
Enhanced oxidative burst in immunologically activated but not elicited polymorphonuclear leukocytes correlates with fungicidal activity; Brummer E et al.; Polymorphonuclear neutrophils (PMN) induced locally in immune mice by intraperitoneal injection of antigen exhibit enhanced fungicidal activity compared with PMN elicited with thioglycolate . The mechanism of the differences in these PMN populations was studied . Sublethal infection was used to produce immunity to Blastomyces dermatitidis . A correlation was sought between the ability of PMN to kill, or not kill, B . dermatitidis and the production of the oxidative burst, as measured by luminol-enhanced chemiluminescence (CL) . Although elicited PMN cocultured with Candida albicans produced a burst of CL and were candidacidal, killing did not occur when PMN were cocultured with B . dermatitidis . Lack of killing of B . dermatitidis by elicited PMN correlated with lack of stimulation of a brisk oxidative burst . In contrast to elicited PMN, PMN induced by B . dermatitidis antigen responded to this fungus with a burst of CL and a significant reduction of inoculum CFU (80%) . Furthermore, these PMN when cocultured with C . albicans produced an enhanced burst of CL, and killing was enhanced compared with that by elicited PMN, e.g., 86 versus 58% . The CL burst and killing of B . dermatitidis by antigen-induced PMN was abrogated in the presence of catalase, implying a critical role for hydrogen peroxide . Partial but significant depression of CL and killing in the presence of dimethyl sulfoxide, a hydroxyl radical scavenger, identified hydroxyl radical, or its metabolites, as a toxic product(s) responsible for a significant fraction of fungicidal activity . These results indicate that the metabolic activity and microbicidal activity of PMN can be altered (enhanced) at the site of an immunological reaction and thus could constitute an important factor in resistance.

Infect Immun, 1985 Aug, 49(2), 298 - 304
Dissociation between interleukin-1 and interleukin-2 production in proliferative response to microbial antigens: restorative effect of exogenous interleukin-2; Vismara D et al.; The relationship between the production of interleukin-1 (IL-1) and interleukin-2 (IL-2) after stimulation of human mononuclear cells within an antigenic extract from Candida albicans was analyzed in both responder and nonresponder donors . Culture supernatants from responders contained both IL-1 and IL-2 activity, whereas the supernatants from nonresponders contained only IL-1 and no appreciable IL-2 . However, the addition of exogenous IL-2 to nonresponder cultures restored the normal proliferative response . Similar observations were made when cells from mice infected intravenously with high doses of Mycobacterium bovis BCG were cultured; these cells showed a marked impairment of the proliferative response to purified protein derivative . Spleen cells from BCG-induced unresponsive mice failed to produce IL-2 despite the fact that normal IL-1 activity was present in the culture . Again, the addition of exogenous IL-2 fully reversed the proliferative unresponsiveness . Thus, the presence of IL-1 does not necessarily induce production of IL-2, and the proliferative unresponsiveness is therefore due to a primary lack of IL-2.

Am J Obstet Gynecol, 1985 Aug 1, 152(7 Pt 2), 921 - 3
Importance of differential diagnosis in acute vaginitis; Sweet RL; Acute vaginitis is one of the most common diseases seen in the practice of office gynecology . Large survey studies of women with lower genital tract symptoms suggestive of vaginitis have demonstrated the presence of three major etiologic categories in acute vaginitis: (1) nonspecific vaginosis (Gardnerella vaginalis), (2) vulvovaginal candidiasis (Candida albicans), and (3) trichomoniasis (Trichomonas vaginalis) . Effective treatment of acute vaginitis requires that an accurate diagnosis be established and etiologic microorganism(s) be identified . In general, the differential diagnosis of acute vaginitis does not rely on elaborate technology but, rather, requires inexpensive and readily available office equipment and supplies, a detailed history, and an adequate examination of the external genitalia, vagina, and cervix . Only after the etiology of vaginitis has been identified can appropriate therapeutic intervention(s) be utilized.

Clin Exp Immunol, 1985 Aug, 61(2), 425 - 32
Age-dependent alterations of Fc gamma receptor-mediated effector functions of human polymorphonuclear leucocytes; Fulop T Jr et al.; Changes in the effector functions in polymorphonuclear leucocytes (PMNL), harvested from blood of young and aged healthy subjects of both sexes, were studied . FC gamma-receptor (Fc gamma R)-mediated incorporation of IgG coated 51Cr-HRBC significantly increased in the aged male group, while the phagocytosis of pre-opsonized fungi (Saccharomyces cerevisiae and Candida albicans) was independent of both the age and sex . However, the intracellular killing capacity of neutrophils obtained from aged male subjects significantly decreased toward 51Cr-labelled c . albicans . The antibody-dependent cellular cytotoxicity (ADCC) was also impaired with ageing in both sexes . The age-dependent decrease in the effector functions of PMNL may be explained, among others, by the fact that during yeast cell incorporation the increased cAMP level does not return to the basic level in the old group . On the other hand, the cGMP level which increased in PMNL of aged subjects does not show any progressive increase as in the young subjects, but remains unchanged . The oxidative metabolism producing free radicals being necessary for the effective intracellular killing and ADCC diminished in PMNL of aged subjects of both sexes . The above findings indicate that the adaptation of cyclic nucleotide system and the oxidative burst to the cell activation becomes impaired with ageing.

Infect Immun, 1985 Aug, 49(2), 435 - 9
Oxidative metabolic response and microbicidal activity of human milk macrophages: effect of lipopolysaccharide and muramyl dipeptide; Cummings NP et al.; Mouse macrophages can be primed by exposure in vitro to the bacterial products lipopolysaccharide and muramyl dipeptide (MDP) or in vivo by injection of MDP, so that they produce more of the bactericidal agent superoxide anion (O2-) when stimulated by phagocytosis or by contact with phorbol myristate acetate (PMA) . Because little is known about the physiology of human tissue macrophages, we examined release of O2- by milk macrophages obtained from 45 normal women for the ability to undergo priming for greater O2- release . In samples from the same individuals, PMA-stimulated O2- release was similar from colostrum (0 to 3 days postpartum) or from transitional milk (5 to 8 days) . Release of O2- by milk macrophages was almost identical to that by blood monocytes from the same women . Milk macrophages phagocytized and killed Candida albicans relatively effectively . Incubation with lipopolysaccharide activated the macrophages in that they were primed for greater PMA-stimulated O2- release . Incubation with the adjuvant MDP or its analog 6-O-(2-tetradecylhexadecanoyl)-MDP did not prime, but incubation with a second analog, 6-O-(stearoyl)-MDP, primed the macrophage for greater O2- release . These results indicated that human tissue macrophages can be primed for greater oxidative response by exposure to bacterial products . Potential exists for the therapeutic use of such immunomodulating agents in the enhancement of host defense.

Biochem Int, 1985 Aug, 11(2), 171 - 6
Steroid binding protein(s) in yeasts; Das M et al.; A progesterone binding protein has been detected in the cytosol prepared from glucose grown cells of both Candida albicans and Saccharomyces cerevisiae . The specific activity of this binding protein is much higher in C . albicans, a pathogenic yeast as compared to the non-pathogenic yeast S . cerevisiae.

Biochem Biophys Res Commun, 1985 Jul 31, 130(2), 885 - 91
Siderophore production by the pathogenic yeast, Candida albicans; Ismail A et al.; Biochemical assays were used to determine that some strains of Candida albicans were capable of simultaneous secretion of both the hydroxamate and phenolate-type siderophores when grown in a deferrated medium at 37 degrees C . All isolants of C . albicans released hydroxamate-type siderophores into the culture medium; whereas, approximately 40% of the strains simultaneously secreted phenolate-type siderophores . The presence of phenolate and hydroxamate-type siderophores in the culture medium was further confirmed by assaying the culture media with type specific siderophore-dependent bacterial auxotrophs . This is the first report showing production of both classes of siderophores by a pathogenic yeast.

Infect Immun, 1985 Jul, 49(1), 172 - 81
Immunoregulation in experimental murine candidiasis: specific suppression induced by Candida albicans cell wall glycoprotein; Carrow EW et al.; Immune regulation in candidiasis is inferred from studies of both human and animal infection, with a suppressive role suggested for cell wall polysaccharide . To study the immunosuppressive potential of Candida albicans in a murine model, whole blastoconidia or purified cell wall components of C . albicans were tested for their effects on the development of acquired immune responses by superimposing a pretreatment regimen upon an established immunization protocol . CBA/J or BALB/cByJ mice were pretreated twice intravenously with 100 micrograms of mannan (MAN), 100 or 200 micrograms of glycoprotein (GP), or 5 X 10(7) heat-killed C . albicans blastoconidia, followed 1 week later by an immunization protocol of two cutaneous inoculations of viable C . albicans blastoconidia given 2 weeks apart . Delayed hypersensitivity (DTH) to GP or to a membrane-derived antigen, B-HEX, was tested 7 days after the second inoculation, and lymphocyte stimulation was tested with mitogens and Candida antigens after 12 days . To assess protection, mice were challenged intravenously with viable C . albicans blastoconidia 14 days after the second cutaneous inoculation and sacrificed 28 days later for quantitative culture of kidneys and brains . Sera were obtained for enzyme-linked immunosorbent assays at selected intervals . Pretreatment with GP resulted in specific in vivo suppression of DTH to GP but not to B-HEX antigen and specific in vitro suppression of lymphocyte stimulation to GP but not to other Candida antigens or mitogens . MAN and heat-killed C . albicans blastoconidia had no such effects . GP pretreatment also diminished the protective effect of immunization against challenge, demonstrable in the brain, while not altering significantly the production of antibody in response to infection . Contrary to clinical evidence, MAN was not immunosuppressive in this model, and in fact, the immunosuppressive potential of GP, which is composed largely of MAN, was found to be dependent upon the presence of its heat-labile protein moiety.

Ann Inst Pasteur Immunol, 1985 Jul-Aug, 136D(1), 29 - 36
Dissociation between cell-mediated immunity and acquired resistance in systemic murine candidiasis; Hurtrel B et al.; Mice immunized with 10(7) heat-killed (HK) Candida albicans injected subcutaneously with or without BCG, used as an immunoadjuvant, were able to develop strong significant delayed-type hypersensitivity (DTH) against C . albicans but without any increase in specific resistance, as measured by median survival time and enumeration of yeasts inside target organ such as lungs, liver, spleen and kidneys after an intravenous (i . v.) challenge of 1 X 10(6) live C . albicans . Concomitant activation of the mononuclear phagocytic system, measured in vivo by increased resistance to L . monocytogenes, was shown to be induced in immune mice challenged i . v . with 1 X 10(6) HK C . albicans . These results are in favour of a clear distinction between DTH and acquired resistance to systemic candidiasis, even in the presence of specific activation of macrophages.

Antimicrob Agents Chemother, 1985 Jul, 28(1), 118 - 22
Chemical parameters, antimicrobial activities, and tissue toxicity of 0.1 and 0.5% sodium hypochlorite solutions; Cotter JL et al.; ffe chemical parameters, antimicrobial activity, and tissue toxicity of two sodium hypochlorite (NaOCl) solutions buffered to a physiologic pH were studied . Initially, a 0.5% NaOCl solution buffered with 3 g of NaH2PO4 per liter was examined . The solution had a pH of 7.49 and an osmolality of 352 mOsmol/liter . When compared with unbuffered and NaHCO3-buffered 0.5% NaOCl solutions, the NaH2PO4-buffered solution was significantly more effective in killing Staphylococcus aureus in vitro . However, the pH of the NaH2PO4-buffered solution decreased over time with a concomitant decrease in antibacterial activity . A freshly prepared solution decontaminated human cadaveric skin colonized by S . aureus, Pseudomonas aeruginosa, or Candida albicans in vitro within 10 min of exposure, whereas a 24-h-old solution cleared the skin of organisms within 15 min . When gauze soaked with 0.5% NaOCl was applied to guinea pig skin for 2 weeks, a 15% decrease in basal cell viabilities was noted . Because of the pH instability and basal cell toxicity, a 0.1% NaOCl solution buffered with NaH2PO4-Na2HPO4 was evaluated . This solution had an osmolality of 386 mOsmol/liter and a pH of 7.4 that was stable over 1 week . A freshly prepared 0.1% NaOCl solution decontaminated skin colonized with S . aureus, C . albicans, and P . aeruginosa within 10, 20, and 30 min, respectively . A 24-h-old solution did not completely decontaminate the colonized skin but significantly reduced the number of microorganisms on the skin surface (P less than 0.001) . Application of this solution of guinea pig skin for 2 weeks produced no significant effect on basal cell viabilities . These solutions may serve as alternative topical agents for use in burn therapy.

Z Naturforsch {C}, 1985 Jul-Aug, 40(7-8), 539 - 50
{Comparison of various immune surface labeling methods for scanning electron microscopy with the example of a surface antigen protein of the yeast Candida albicans}; Borg M; The labeling of immunocomplexes for scanning electron microscopy (SEM) is a fairly new technique, and the various procedures, that have been proposed, have not yet been compared . Such comparative evaluation was performed with Candida protease as a target antigen . This secretory enzyme of the opportunistic yeast Candida albicans can be localized on the surface of fungal blastopores and mycelia, both after growth in proteinaceous medium and upon infection of murine peritoneal macrophages . The presence of the protease antigen was confirmed by immunofluorescence and by immunoperoxidase-light microscopy . The decoration of protease - anti protease complexes for SEM was attempted with colloids derived from the immunoperoxidase reaction, by the immunogold technique, and by antibodies linked to beads of synthetic polymers (polystyrene, polymethacrylate, polyacrolein) . In addition, inactivated Staphylococcus aureus was used, which binds to antibodies through its protein-A . The high resolution by SEM of surface structures was matched only by the colloid based decoration techniques . All conjugates with beads suffered from inconsistent binding, which did not correspond with the distribution of the surface antigen . The comparatively best result with beads was obtained with polystyrene (Latex) . Colloid based techniques in addition allow for critical point drying, which cannot be applied to synthetic beads in the usual manner.

Mycopathologia, 1985 Jul, 91(1), 3 - 15
The programs of protein synthesis accompanying the establishment of alternative phenotypes in Candida albicans; Finney R et al.; Under the regime of pH-regulated dimorphism, stationary phase cells of the dimorphic yeast Candida albicans can be induced to form exclusively and synchronously ellipsoidal buds or elongate mycelia at the same temperature and in the same nutrient medium, the sole determinant of phenotype in this case being pH . Employing pH-regulated dimorphism, cells were pulse-labeled with {35S}-methionine during three consecutive intervals encompassing the preevagination period, the period including evagination and phenotypic commitment, and the post-evagination period . Labeled polypeptides were analyzed by 2D-PAGE . Of the 374 polypeptides examined, the majority (237) did not differ significantly in relative incorporation between the three pulse periods and were similar between budding and mycelium-forming populations . Sixty polypeptides were labeled at negligible or relatively low levels during the first pulse period, but at significantly higher levels during the second and third or third pulse periods . All but one were similar between budding and mycelium-forming populations . Seventeen polypeptides were synthesized at relatively high levels during the first pulse period, but at reduced or negligible levels during the second and third or third pulse periods . All but one were similar between budding and mycelium-forming populations . Only two polypeptides were found to be associated exclusively with mycelium-forming cultures, two associated exclusively with budding cultures, and two enriched significantly in budding cultures of wild-type cells . Employing a variant, MD20, which forms buds at both low and high pH, it was demonstrated that only one mycelium-associated polypeptide and only one bud-associated polypeptide are phenotype rather than pH-specific . Limits to this method of phenotype comparison are outlined, and the unusual similarity rather than dissimilarity in the programs of gene expression between the diverging populations considered in terms of phenotypic regulation.

Mycopathologia, 1985 Jul, 91(1), 17 - 22
Systemic candidiasis in mice immunized with Candida albicans ribosomes; Levy R et al.; In view of our previous findings that vaccination of mice with Candida albicans ribosomes protects them against experimental systemic candidiasis, the aim of this study was to investigate the effect of this vaccination on the course of infection in immunized animals . Since the kidney is the major target in systemic candidal infection, we concentrated in this research on studying the histopathology and determining quantitatively the candidal colonization of this organ . The experiments were carried out at various time intervals after intravenous inoculation with live C . albicans . The colonization of kidneys in immunized mice was markedly lower than that in controls . The maximal difference in renal colonization between immunized and non immunized animals was observed when relatively low challenge doses were used . The inhibition of candidal multiplication in immunized mice seemed to be correlated to their increased resistance against lethal challenge, as expressed by a significantly higher survival rate . Histopathological changes and fungal elements were found in kidneys of control mice as early as 20 h post infection, while the kidneys of immunized mice did not seem affected by the disease . Moreover, even 3 days post infection, the kidneys of vaccinated animals still seemed normal . In conclusion, apparently the ribosomal vaccination leads to diminished colonization of the major site of infection in candidiasis, thus affording protection to the immunized animals against these infections.

J Gen Microbiol, 1985 Jul, 131 ( Pt 7), 1595 - 602
Effect of allylamine antimycotic agents on fungal sterol biosynthesis measured by sterol side-chain methylation; Ryder NS; Sterol side-chain (C-24) methylation was assayed by incorporation of radioactivity from {Me-14C}methionine into the ergosterol fraction in cells of the pathogenic fungi Candida albicans, Candida parapsilosis and Trichophyton mentagrophytes . Methylation at C-24 occurred after nuclear demethylation in all cases . The method was used to measure ergosterol biosynthesis inhibition by the allylamine antimycotics naftifine and SF 86-327, which are known to block squalene epoxidation . In C . albicans cells treated with SF 86-327 (1 mg l-1) to fully inhibit squalene epoxidation, C-24 methylation continued for several hours at about 40% of the control rate . This residual biosynthesis was probably due to methylation of endogenous sterol precursors . The degree of residual biosynthesis in the three fungi correlated well with their susceptibility to SF 86-327 . The highly susceptible dermatophyte T . mentagrophytes had negligible residual sterol biosynthesis . These differences were not due to inhibition of methionine uptake . For naftifine (100 mg l-1) there was evidence of a second inhibitory action in C . albicans . A cell-free assay indicated that this was due to direct inhibition of the C-24 methyltransferase.

Infect Immun, 1985 Jul, 49(1), 207 - 11
Correlation of binding of rabbit granulocyte peptides to Candida albicans with candidacidal activity; Lehrer RI et al.; NP-1, a candidacidal peptide purified from rabbit granulocytes, bound extensively and with biphasic kinetics to Candida albicans . The primary phase of binding was temperature independent and occurred even at 0 degrees C . This primary binding was relatively specific, reversible, saturable, and of high capacity . It was inhibited by increased salt concentrations in the incubation medium, but was relatively unaffected by increasing the calcium ion concentration or by lowering the incubation temperature to 0 degrees C . The secondary phase of binding was only noted under conditions that supported candidacidal activity . Secondary binding was inhibited by millimolar concentrations of calcium, but not magnesium, ions and did not occur at 0 degrees C or when subtoxic concentrations of NP-1 were tested . NP-2 and NP-3a, other potent candidacidal peptides from rabbit granulocytes, also bound directly and extensively to C . albicans and competed for binding with NP-1 . NP-4 and NP-5, less candidacidally active homologs of the aforementioned peptides, showed relatively little direct binding activity and competed poorly for binding with NP-1 or NP-2 . NP-3b, another less candidacidal homolog, bound extensively to C . albicans, but did not compete effectively with NP-1 or NP-2 . By comparing candidacidal and binding activity of the peptides, we conclude that the candidacidal activity of NP-1 involves primary binding to C . albicans followed by postbinding events that are temperature dependent and inhibitable by calcium ions.

Infect Immun, 1985 Jul, 49(1), 202 - 6
Activity of rabbit leukocyte peptides against Candida albicans; Selsted ME et al.; Six related cysteine-rich, low-molecular-weight peptides were purified from rabbit peritoneal granulocytes and tested in vitro for fungicidal activity against Candida albicans . Two peptides (NP-1 and NP-2) were highly effective, one (NP-3a) was moderately active, and three (NP-3b greater than NP-4 much greater than NP-5) had substantially less potency . There was a general, but imperfect, correlation between the candidacidal potency of each peptide and its net cationic charge . Candidacidal activity by NP-1 was concentration and time dependent and occurred rapidly under optimal low-ionic-strength conditions . It was inhibited by increasing either the ionic strength or Ca2+ concentration of the incubation mixtures, but was relatively unaffected by Mg2+ . Candidacidal activity was independent of H+ concentrations between pH 5 and 8, but decreased below pH 5 . Candidacidal activity was temperature sensitive and was virtually abolished when NP-1 was incubated with C . albicans at 0 degrees C . Cysteine-rich antimicrobial peptides such as NP-1 and NP-2 may equip leukocytes to deal with infections caused by C . albicans and other fungi that are susceptible to their microbicidal effects.

Oral Surg Oral Med Oral Pathol, 1985 Jul, 60(1), 30 - 4
A prospective follow-up study of 570 patients with oral lichen planus: persistence, remission, and malignant association; Silverman S Jr et al.; Five hundred seventy patients with oral lichen planus were followed for periods ranging from 6 months to more than 10 years (mean, 5.6 years) . The mean age was 52 years, and 67% of the patients were women . Erosive lichen planus was the most frequent clinical form, and the buccal mucosa was the most common site . Of the 75% patients treated with corticosteroids, 29% experienced complete remission and 63% had partial remission while maintained on medication . Fewer than 3% experienced spontaneous remission . Malignant transformation occurred in 7 patients (1.2%) in a mean time of 3.4 years after the onset of lichen planus . The onset of lichen planus could not be associated with any evident factors, such as family history, Candida albicans, glucose intolerance, and smoking.

J Infect Dis, 1985 Jul, 152(1), 33 - 42
Mechanisms of resistance of Aspergillus fumigatus Conidia to killing by neutrophils in vitro; Levitz SM et al.; Despite the critical role for neutrophils in host defenses against invasive aspergillosis, previous studies have established that neutrophils are unable to kill resting conidia of Aspergillus fumigatus . The mechanisms of resistance of the conidia were therefore investigated . Electron microscopy studies showed the fusion of phagosomes containing A . fumigatus conidia with lysosomes of the neutrophil . Resting conidia of A . fumigatus were then compared with those that had been preincubated in broth until swollen, but not germinated, as well as with blastospores of Candida albicans (two fungal forms that are killed by neutrophils) and zymosan particles . Despite comparable susceptibility to phagocytosis, resting conidia of A . fumigatus stimulated production of significantly less superoxide anion, hydrogen peroxide, and hypochlorous acid and induced less myeloperoxidase-dependent iodination by neutrophils than did the preincubated conidia of A . fumigatus, blastospores of C . albicans, or zymosan particles . In addition, resting conidia of A . fumigatus were relatively resistant to cell-free killing by oxidants presumed to be generated by neutrophils . Thus, resistance of resting conidia of A . fumigatus to neutrophil fungicidal mechanisms appears to be secondary to both failure of the conidia to stimulate an optimal respiratory burst as well as resistance of the conidia to neutrophil oxidants . However, the reversal of this resistance by preincubation of the conidia suggests that neutrophils still may form an important host defense against the conidia of A . fumigatus.

Cell Immunol, 1985 Jul, 93(2), 532 - 40
Antigen-dependent heterogeneity of human migration inhibitory factor; Weiser WY et al.; Human migration inhibitory factor (MIF) produced by peripheral blood mononuclear cells stimulated with purified protein derivative, tetanus toxoid, streptokinase-streptodornase, or Candida albicans antigen was analyzed by gel filtration and isoelectrofocusing . In all cases, supernatants harvested after a 24-hr exposure of the mononuclear cells to the antigen yielded only one MIF species with an isoelectric point of 5 . In contrast, isoelectrofocusing of supernatants obtained from cells exposed to the antigen for an additional 24 hr demonstrated that different antigens induce the elaboration of different MIF species . Streptokinase-streptodornase and tetanus toxoid induced the production of one MIF species with an isoelectric point of 5 (pH 5-MIF) . Stimulation of cells with Candida antigen elaborated a MIF species with an isoelectric point of 3 (pH 3-MIF) . In contrast, stimulation of cells with purified protein derivative induced the production of both pH 3-MIF and pH 5-MIF.

S Afr Med J, 1985 Jun 29, 67(26), 1044 - 5
Ketoconazole prophylaxis in patients with solid tumours receiving aggressive immunosuppressive therapy . An open randomized comparison between 200 mg/d and 400 mg/d doses; Scrimgeour E et al.; Forty-three patients, most with solid tumours, were included in a study comparing the antifungal prophylactic effect of ketoconazole (Nizoral; Janssen) 200 mg/d and 400 mg/d during the period of immunosuppressive therapy . Seven patients were not seen for follow-up and 6 died of their underlying disease without clinical evidence of mycosis . Twelve of the patients who could be evaluated received ketoconazole 200 mg/d and 18 received 400 mg/d . No infections occurred during the period of prophylactic treatment . In the group receiving 200 mg/d 10 of 36 cultures (28%) were positive for Candida albicans before prophylaxis . During prophylaxis 5 of 18 cultures (28%) were positive and at the end of the prophylactic regimen 1 out of 37 cultures (3%) was positive . In the 400 mg/d group, 13 of 47 cultures (28%) were positive at the start, 2 out of 20 (10%) were positive during prophylaxis and 1 out of 45 (2%) was still positive at the end . The drug was clinically well tolerated . Twenty of the 30 evaluable patients had no significant biochemical abnormalities, 5 had an increased serum transaminase level, 2 had an increased alkaline phosphatase level, and 3 had combined increases of serum transaminase and alkaline phosphatase levels . These abnormalities are regularly seen in patients with metastatic malignant disease, and are not necessarily related to the ketoconazole prophylaxis.

J Biol Chem, 1985 Jun 10, 260(11), 6782 - 7
The kinetics and divalent cation inhibition of plasma membrane ATPase in the yeast Candida albicans; Hubbard MJ et al.; The kinetics of ATP hydrolysis and cation effects on ATPase activity in plasma membrane from Candida albicans ATCC 10261 yeast cells were investigated . The ATPase showed classical Michaelis-Menten kinetics for the hydrolysis of Mg X ATP, with Km = 4.8 mM Mg X ATP . Na+ and K+ stimulated the ATPase slightly (9% at 20 mM) . Divalent cations in combination with ATP gave lower ATPase activity than Mg X ATP (Mg greater than Mn greater than Co greater than Zn greater than Ni greater than Ca) . Divalent cations inhibited the Mg X ATPase (Zn greater than Ni greater than Co greater than Ca greater than Mn) . Free Mg2+ inhibited Mg X ATPase weakly (20% inhibition at 10 mM) . Computed analyses of substrate concentrations showed that free Zn2+ inhibited Zn X ATPase, mixed (Zn2+ + Mg2+) X ATPase, and Mg X ATPase activities . Zn X ATP showed high affinity for ATPase (Km = 1.0 mM Zn X ATP) but lower turnover (52%) relative to Mg X ATP . Inhibition of Mg X ATPase by (free) Zn2+ was noncompetitive, Ki = 90 microM Zn2+ . The existence of a divalent cation inhibitory site on the plasma membrane Mg X ATPase is proposed.

Sabouraudia, 1985 Jun, 23(3), 199 - 206
Experimental chronic vaginal candidosis in rats; Sobel JD et al.; In the past, the rat model of experimental vaginal candidosis has been used to study the efficacy of antifungal agents in eradicating acute vaginitis . In the present study, chronic vaginal candidosis was induced to study the natural history of the infection . Results indicate that chronic infection is readily achieved and is strictly dependent on oophorectomy and hormonal maintenance of pseudoestrous . Histologic studies confirm that rats so infected and with long term vaginal carriage of Candida albicans have true chronic infection with extensive mycelial formation and superficial mucosal invasion.

Sabouraudia, 1985 Jun, 23(3), 189 - 98
Oral treatment with ketoconazole in systemic candidosis of guinea-pigs: microbiology, hematology and histopathology; Van Cutsem J et al.; Non-pretreated Albino guinea-pigs were infected intravenously with Candida albicans and treated orally either with placebo or ketoconazole . The 17-day follow-up of the fungal dissemination was based upon hematology, on gross and microscopic lesions and on the demonstration of the fungus by culture techniques . The efficacy of ketoconazole, both with regard to the quantity and the morphology of fungi in various organs and the tissue-healing process are discussed . The treatment of human systemic candidosis will also be considered . No side-effects due to the therapy were observed in these experiments.

Eur J Clin Microbiol, 1985 Jun, 4(3), 340 - 2
Disseminated candidiasis with extensive folliculitis in abusers of brown Iranian heroin; Calandra T et al.; Two cases of heroin abusers who developed disseminated candidiasis are reported . Cultures of skin lesions revealed Candida albicans, which on histology were shown to be located in and around hair shafts . Both patients recovered after treatment with amphotericin B combined with 5-fluorocytosine and either ketoconazole or dexamethasone . This unusual cutaneous syndrome of candidal infection associated with extensive folliculitis seems to be related to the use of a particular type of heroin, the so-called brown Iranian heroin.

Ann Allergy, 1985 Jun, 54(6), 538 - 40
Irritable bowel syndrome and hypersensitivity to food; Petitpierre M et al.; Food hypersensitivity as a cause of irritable bowel syndrome was investigated by means of exclusion diet and blind provocation . Twelve atopic and twelve non-atopic individuals entered into the study . Skin prick testing with 20 foods and food additives and RAST specific for food only, were done in all cases . Serum IgE level was also measured . In 14 patients one or several food or additives were shown to induce the typical symptoms of IBS . In at least nine cases of atopy, an IgE-mediated mechanism could be incriminated . Among other potential pathogenetic mechanisms, the presence in the intestinal tract of yeast (Candida albicans, Geotrichum candidum) seems to be of major importance . Yeast apparently favor the development of allergic as well as pseudo-allergic reactions, at least in some patients . Finally, at least in atopic patients complaining of IBS, it is of importance to search for a food component . Dramatic clinical improvements can result from the introduction of an adequate exclusion diet.

J Clin Lab Immunol, 1985 Jun, 17(2), 69 - 73
Inflammatory polymorphonuclear neutrophil leukocytes; orientation, chemotactic, locomotor and phagocytic capabilities of neutrophils from the human gingival crevice; Scully C et al.; The chemotactic, chemokinetic and phagocytic capacity of neutrophils from blood and from gingival crevicular washings of the same subjects were compared in visual assays, i.e . time-lapse cinematography and an orientation assay . A high proportion of the cells in both populations was motile, but the mean speed of locomotion of the crevicular cells was lower than that of the blood cells, indicating a relative impairment of chemokinesis . The differences between blood and crevicular cells in their capacity to migrate towards and phagocytose blastospores of Candida albicans in fresh serum were not significant, though crevicular cells were slightly less efficient in orienting towards sources of chemotactic gradients of various factors . Thus there is not a major defect of chemotaxis or phagocytosis of crevicular neutrophils.

J Gen Microbiol, 1985 Jun, 131 ( Pt 6), 1467 - 80
Temporal and spatial differences in cell wall expansion during bud and mycelium formation in Candida albicans; Staebell M et al.; The infectious yeast Candida albicans is capable of growing in either a budding or mycelium form, depending upon the pH of the supporting medium . By monitoring the position of polylysine-coated beads firmly attached to the wall of growing cells, the zones of expansion for the surface of the cell wall have been mapped for the alternative growth forms . Both spatial and temporal differences are demonstrated to exist . During roughly the first two-thirds of bud growth, a very small, highly active apical zone accounts for roughly 70% of surface expansion . The remaining 30% is due to general expansion . When a bud reaches approximately two-thirds of its final surface area, the apical zone shuts down, and subsequent expansion is completed by the general mechanism . During mycelial growth, at least 90% of expansion is due to a small, highly active apical growth zone, and less than 10% is due to the general mechanism . In contrast to budding cells, the apical zone of the growing mycelium never shuts down as long as growth continues in the mycelial form . These distinct temporal and spatial differences in expansion are considered in terms of the regulation of alternative phenotypes in Candida.

J Biol Buccale, 1985 Jun, 13(2), 145 - 66
Ultrastructural relationship of denture surfaces, plaque and oral mucosa in denture stomatitis; Walter B et al.; Denture plaque has been studied by transmission electron microscopy in glycolmethacrylate-embedded specimens from six patients presenting with typical denture stomatitis . Different types of thin and thick pellicles were found applied to the denture surface . These were in contact with a denture plaque made up predominantly of loosely packed Gram- positive and Gram- negative bacteria . Rounded, rod-shaped and filamentous micro-organisms were all evident . Group of Candida albicans with normal ultrastructure were noted in some limited zones . When surrounded by bacteria, especially by bacteria in corn-cob configurations the Candida showed cytological signs of degeneration . In one case out of six a bacterial penetration of the acrylic denture base was observed, through narrow and straight channels and subsurface cavities filled with micro-organisms . Bacterial penetration was also seen in the most superficial cell layers of the palatal mucous membrane.

Immunopharmacology, 1985 Jun, 9(3), 181 - 7
Effect of oral administration of different combinations of killed bacteria on some depressed macrophage functions in tumor-bearing rats; Iannello D et al.; In the present study, we compared the ability of different bacterial species administered orally in various combinations to restore some depressed peritoneal macrophage functions in tumor-bearing rats . Phagocytosis, killing of Candida albicans and chemotactic response of resident peritoneal cells from treated tumor-bearing rats were influenced by different associations of bacteria . In particular, when Staphylococcus aureus was administered together with other bacterial species, the phagocytic activity of peritoneal cells was restored to normal values, and intracellular killing of C . albicans was enhanced . The results are discussed in relation to the possible influence of mucosal bacterial flora on the level of activation of peritoneal macrophages . The possibility that bacterial species can influence in various ways immunocompetent cells in relation to the different chemical composition of some common structures is also discussed.

Z Hautkr, 1985 Jun 1, 60(11), 884 - 96
{Plasmoacanthoma . A contribution to the diagnosis, etiopathogenesis and nosology}; Goring HD et al.; We report on a patient suffering from plasmoacanthoma which started from the right angle of the mouth and extended to the oral mucosa . The clinical tentative diagnosis of a malignant tumor was histologically supported by an immediate frozen section under surgery . Only histological examination of tumor material embedded in paraffin settled the diagnosis of plasmoacanthoma . On the base of mycological demonstration of Candida albicans on the tumor tissue, we discuss etiopathogenetic aspects of plasmoacanthoma as well as its nosologic position.

J Clin Pathol, 1985 Jun, 38(6), 701 - 6
Use of immunoblotting to identify antigenic differences between the yeast and mycelial phases of Candida albicans; Burnie JP et al.; Western blotting was applied to the analysis of Candida albicans in the yeast and mycelial phases in an attempt to recognise mycelial specific antigens which might be of serodiagnostic value . The antisera were prepared in rabbits by immunising them with pressates of C albicans type A NCTC 3153 in the yeast phase or the mycelial phase . These were blotted against C albicans in the yeast and mycelial phases and the yeast phase of C parapsilosis, C krusei, C tropicalis, and Torulopsis glabrata . Cross reactivity was greatest against C parapsilosis . One yeast specific mannoprotein was identified with a molecular weight of 49 000 . No mycelial specific antigens could be identified.

J Bacteriol, 1985 Jun, 162(3), 1024 - 9
Multiplicity of peptide permeases in Candida albicans: evidence from novel chromophoric peptides; McCarthy PJ et al.; Evidence is presented for the presence of multiple peptide permeases in the eucaryotic organism Candida albicans . Instrumental in these studies were the peptides L-alanyl-L-2-thiophenylglycine (Ala-alpha-TPG) and L-alanyl-L-2-thiophenylglycyl-L-alanine (Ala-alpha-TPG-Ala), which contain thiophenol attached to the alpha-carbon of glycine . Subsequent to transport into the fungal cell, enzymatic hydrolysis of these peptides resulted in the release of free thiophenol, which was quantified by using Ellman reagent . Thiophenol release was shown to be directly correlated to peptide transport and hydrolysis, with transport being the rate-limiting step in intact cells . These peptides, whose uptake showed Michaelis-Menten kinetics, have been used to determine peptide uptake in C . albicans . In addition, we found that the intracellular peptidases can readily be assayed in permeabilized cells and that bestatin, an aminopeptidase inhibitor, inhibits all detectable peptidase activity . C . albicans 124 was able to transport and hydrolyze both Ala-alpha-TPG and Ala-alpha-TPG-Ala, whereas the mutant (124NIK5) was able to transport only the tripeptide . The intracellular peptidases of this mutant were unaffected . In wild-type C . albicans 124, oligopeptides were able to compete with uptake of Ala-alpha-TPG-Ala to a far greater extent than with that of Ala-alpha-TPG; dipeptides inhibited uptake of both Ala-alpha-TPG and Ala-alpha-TPG-Ala . These results provide complementary evidence for the existence of distinct transport systems.

Infect Immun, 1985 Jun, 48(3), 806 - 12
Cross-reacting human and rabbit antibodies to antigens of Histoplasma capsulatum, Candida albicans, and Saccharomyces cerevisiae; Kumar BV et al.; Using Western blots of electrophoretically separated antigens, we show that human antibodies react most frequently to antigens shared by three fungi (Histoplasma capsulatum, Candida albicans, and Saccharomyces cerevisiae) . Reactivity to antigens specific for individual fungi was relatively uncommon . The pattern of reactivity could not distinguish infected patients from uninfected controls . Rabbits immunized with extracts of each fungus also produced antibodies to cross-reactive or shared antigens of the other two fungi . Furthermore, preimmune sera showed similar but lower reactivity with the same fungal antigens . We believe that the preimmunization antibodies, which probably resulted from earlier fungal colonization or inapparent infections, predisposed the immune responses elicited by the vaccinations . A similar mechanism likely explains the results with human sera.

Schweiz Med Wochenschr, 1985 Jun 1, 115(22), 764 - 7
{Importance of early retinal fluorescein angiography in candidiasis in drug addicts}; Mersch MH et al.; Three cases of Candida albicans endophthalmia in drug addicts are reported . Three important signs suggestive of a fungal etiology for choroiditis are discussed: location of the granuloma at the end of a macular arteriole, early leak of fluorescein to the vitreous body, and solitary papillitis.

J Hosp Infect, 1985 Jun, 6(2), 154 - 7
The growth of micro-organisms in intravenous fluids; Garcia-Caballero J et al.; The growth of four micro-organisms in 12 different intravenous fluids at room temperature was studied . Gram-negative organisms grew better than Gram-positive, and lipid solutions were most favourable to microbial growth . Microbial growth was inhibited in solutions with osmolalities over 500 mosmol/l; Staphylococcus epidermidis was inhibited by inocula with Gram-negative bacilli, while the growth of Gram-negative bacilli generally was not affected . Candida albicans was inhibited by Gram-negative bacilli in lipid and 5% dextrose solutions.

Acta Med Okayama, 1985 Jun, 39(3), 191 - 7
Candida-induced histamine release from basophils: relationship to house dust- and anti-IgE-induced secretion; Tanizaki Y et al.; Candida albicans-induced histamine release from basophils was studied in 54 patients with bronchial asthma in comparison with the release caused by house dust and anti-IgE . The release of histamine induced by C . albicans and that induced by house dust were closely related to the serum levels of specific IgE antibodies as expressed by RAST scores . A correlation of C . albicans-induced histamine release with the release caused by anti-IgE was not generally observed . On the other hand, a close correlation was found between house dust- and anti-IgE-induced histamine release . It was suggested from these results that the differences between C . albicans- and house dust-induced histamine release might be due to the different antigenicity of the two allergens.

Am J Ophthalmol, 1985 May 15, 99(5), 534 - 8
Excimer laser therapy for experimental Candida keratitis; Serdarevic O et al.; In vivo treatment of experimental Candida albicans keratitis with the excimer laser achieved sterilization on culture and histopathologically in all corneas in which clinically visible infiltration was removed with the laser at the 193-nm wavelength . Treatment at the 248-nm wavelength was not successful in eradicating infection compared with untreated controls . The 193-nm wavelength is highly effective, probably because infected tissue is totally removed by ablative photodecomposition . At the 248-nm wavelength, thermal effects become more dominant and, therefore, fungal elements are incompletely ablated . Light microscopy two days after treatment at the 193-nm wavelength showed healing of ulcerated areas, fine basophilic stippling at the epithelial-stromal interface, and undamaged underlying stroma.

What Is Yeast?, What Is Biofilm?, What Is Genetic Engineering?, What Is Biotechnology?, What Is Nitrification?, i, Bacterium, a, Microbiology, n, Bacteriology, s, Microorganisms, s, Bacteria, i, Antimicrobials, o, Salmonella, e, Escherichia coli, r, Klebsiella, n, Candida albicans, r, Bacteria, r, Escherichia coli, e, Bacteriological, e, Vibriosis, n, Antimicrobials, r, Staphylococcus, s, Biodegradation, s, Bacteriophage, o, Escherichia coli, o, Salmonella, o, Corynebacter, e, Streptococcal, a, Microbiological, e, Staphylococcus, n, Escherichia coli, e, Microbial

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005