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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 ce |