Candida albicans

Carbohydr Res, 1989 Apr 15, 187(2), 239 - 53
Structural analysis of phospho-D-mannan-protein complexes isolated from yeast and mold form cells of Candida albicans NIH A-207 serotype A strain; Shibata N et al.; The immunochemical properties between phospho-D-mannan-protein complexes of yeast (Y) and mycelial (M) forms of Candida albicans NIH A-207 (serotype A) strain were compared . Hydrolysis of the Y-form complex gave a mixture of beta-(1----2)-linked D-mannooligosaccharides consisting mainly of tri- and tetra-ose, whereas the M-form complex gave preponderantly D-mannose . The antiserum against Y-form cells exhibited a lower reactivity with the M-form than with the Y-form complex, whereas the antiserum to M-form cells could not distinguish significantly between both complexes . Moreover, these acid-modified complexes showed lower antibody-precipitating effect than each corresponding intact complex against antisera of Y- and M-form cells . Digestion of the acid-modified Y- and M-form complexes with the Arthrobacter GJM-1 strain alpha-D-mannosidase yielded 35- and 40-% degradation products, respectively . Acetolysis of each modified complex under mild conditions gave the same D-mannohexaose, beta-D-Manp-(1----2)-beta-D-Manp-(1----2)-alpha-D-Manp -(1----2)-alpha-D-Manp- (1----2)-alpha-D-Manp-(1----2)-D-Man . Because the complexes of Y- and M-form cells of C . albicans NIH B-792 (serotype B) strain did not give any hexaose fraction containing beta-(1----2) linkages, the presence of this hexaose can be regarded as one of the dominant characteristics of the serotype-A specificity of C . albicans spp.

J Fla Med Assoc, 1989 Apr, 76(4), 386 - 7
Primary cutaneous infections with candida species associated with percutaneous intravenous catheters in patients with cancer; Spiers AS; Long-term percutaneous intravenous catheters have added greatly to the comfort of cancer patients who receive intensive therapy, but the resulting breach in body defenses contributes to infection . Staphylococcus epidermidis has been a prominent infecting organism, and recently aspergillus species have been reported in association with Hickman lines . Two patients are reported with yeast infection: Candida parapsilosis with a Groshong catheter and Candida albicans with a Hickman catheter . In immunocompromised patients such infections are potentially life-threatening and may reinforce the case for totally implanted venous access devices overlaid by intact skin.

Nebr Med J, 1989 Apr, 74(4), 73 - 5
Co-infection with Legionella pneumophila and Pneumocystis carinii in a patient with chronic lymphocytic leukemia; Dworzack DL et al.; A patient with chronic lymphocytic leukemia was found to have pneumonitis caused by a simultaneous Pneumocystis carinii and Legionella pneumophila infection . Although both microorganisms frequently cause pulmonary infections in immunocompromised patients, co-infection has not been reported . This patient responded to antimicrobial therapy, but superinfection with Candida albicans led to his death . As there are numerous infective and noninfective causes of pneumonia in such patients, this case illustrates that the identification of a single etiologic agent does not obviate the search for other potential causes.

Yeast, 1989 Apr, 5 Spec No, S465 - 70
Long-chain alcohol production by yeasts; White MJ et al.; Fourteen yeast strains from six genera were analysed for the presence of long-chain alcohols, the highest levels being found in Candida albicans . The major alcohols synthesized were saturated, primary alcohols with C14, C16 or C18 chain length with relative proportions of C16 greater than C18 greater than C14 . In C . albicans synthesis of long-chain alcohols occurred only after the end of exponential growth . Long-chain alcohol contents were lower in organisms grown aerobically as compared with anaerobically and contents of all three classes increased as the concentration of glucose was raised from 1.0 to 30.0% (w/v) . In anaerobic cultures greatest alcohol contents were obtained using medium containing 10% (w/v) glucose . Substituting glucose (10%, w/v) with the same concentration of galactose in aerobic cultures greatly decreased contents of long-chain alcohols, while inclusion of 10% (w/v) glycerol virtually abolished their synthesis . Supplementing anaerobic cultures with odd-chain fatty acids induced synthesis of odd-chain alcohols, Nitrogen limitation induced long-chain alcohol synthesis in aerobically grown Candida maltosa and quantities were increased with conditions of glucose excess and nitrogen limitation.

FEMS Microbiol Lett, 1989 Apr, 49(2-3), 329 - 33
Rapid identification of medically important yeasts by electrophoretic protein patterns; Bruneau S et al.; A simple electrophoretic method for yeast identification was evaluated . Whole cells were extracted by SDS and the protein profiles obtained in SDS-PAGE after Coomassie blue staining were compared for 52 strains from 9 species of yeast or yeast-like fungi commonly isolated from man (Candida albicans, C . glabrata, C . guilliermondii, C . krusei, C . parapsilosis, C . pseudotropicalis, C . tropicalis, Geotrichum candidum, Saccharomyces cerevisiae) . The corresponding patterns showed 30 to 45 polypeptides in the range 95-20 kDa and were clearly different for the 9 species . No differences could be detected between strains from the same species . The characteristic patterns were obtained within 24 h allowing rapid identification of the most commonly encountered clinical yeast isolates.

Scand J Immunol, 1989 Apr, 29(4), 391 - 8
Opioid peptides modulate the organization of vimentin filaments, phagocytic activity, and expression of surface molecules in monocytes; Prieto J et al.; It is theorized that intermediate filaments are important in the modulation of membrane activity and cell motility; however, their functions are unknown . The assembly and organization of these filaments are under hormonal regulation . We investigated in human monocytes the in vitro effects of Met-enkephalin, Leu-enkephalin, and beta-endorphin on the expression of immunoreactive cytoskeletal vimentin filaments . We simultaneously examined their effect on the phagocytosis of Candida albicans and on the membrane display of surface molecules . The three opioid peptides markedly reduced the expression of vimentin filaments, the phagocytic activity, and the display of HLA-DR molecules at concentrations of 10(-6), 10(-8), and 10(-10) M . On the other hand, the intravenous administration of fentanyl, a synthetic opiate agonist, to patients undergoing surgery induced similar changes in monocytes . In other experiments, 10(-8) M beta-endorphin also decreased the expression of CR3 but did not influence the display of CD13, a surface protein of unknown function . Expression of vimentin filaments correlated directly with the display of HLA-DR antigens and CR3 and with the phagocytic activity . The results of this paper indicate that opiates and opioids, neuropeptides known to be released during stress, can directly depress several monocyte functions . Furthermore, from these data it may be speculated that intermediate filaments may regulate the membrane expression of some surface molecules and the phagocytic process.

Pediatr Pol, 1989 Apr, 64(4), 223 - 8
{Pimafucin in the treatment of mycoses of the oral cavity in children with chronic blood diseases}; Rokicka-Milewska R et al.; 2.5% solution in the form of oral drops (Gist-brocades) has been used in the treatment of Candida albicans infections of the mucous membranes in children with chronic blood diseases . Out of 34 children 28 recovered completely which is 82.3% of all cases . The highest effectiveness of the preparation was found in the group of children with acute infections . In all cases of chronic candidiasis the improvement of the clinical condition was obtained . Only few children have not shown the growth of Candida albicans in the control investigations.

J Gen Microbiol, 1989 Apr, 135 ( Pt 4), 957 - 66
Factors influencing the haematoporphyrin-sensitized photoinactivation of Candida albicans; Bertoloni G et al.; Photosensitizing activity of haematoporphyrin (Hp) on Candida albicans cells is mainly promoted by unbound dye molecules in the bulk aqueous medium . Moreover, the death of photosensitized cells is dependent on the dye concentration, irradiation time, irradiation temperature, and the composition of the growth media . Morphological and biochemical studies indicate that the photoprocess involves an initial limited alteration of the cytoplasmic membrane, which allows the penetration of the dye into the cell with consequent photodamage of intracellular targets . In this respect, the Hp-sensitized photoinactivation of eukaryotic microbial cells differs from that in prokaryotic cells.

Cesk Farm, 1989 Apr, 38(3), 139 - 40
{Inhibition of Candida albicans transformation from the yeast form to the mycelial form by 2-alkylthio-6-amino- and 2-alkylthio-6-formamido- benzothiazoles}; Kuchta T et al.; The inhibitory effectiveness of 2-alkylthio-6-amino- and 2-alkylthio-6-formamidobenzothiazoles (19 derivatives altogether) on the transformation of the yeast-like form of Candida albicans into the mycelial form (1 strain from the collection and 2 clinical isolates) was investigated . Most derivatives tested, similarly as the standard 2-mercaptobenzothiazole (Dermacid), did not exert any difference between the inhibitory effectiveness on filamentation and the inhibition of the growth and reproduction of the yeast-like form . However, the best derivative, 6-amino-2-n-pentylthiobenzothiazole, showed as much as 25-fold higher inhibitory effectiveness on the transformation of the yeast-like form into the mycelial one than MIC.

Mycopathologia, 1989 Apr, 106(1), 1 - 3
Detection of Candida albicans in disseminated candidosis by immunofluorescence staining; Reijula KE; An indirect immunofluorescence (IF) method using rabbit anti-Candida albicans was used to detect C . albicans in blood samples of 12 patients with systemic candidosis defined clinically, histologically and by blood cultures . Positive staining of C . albicans could be detected in all of the patients . The findings suggest that IF-method offers a more rapid method in the diagnosis of disseminated candidosis.

Yeast, 1989 Apr, 5 Spec No, S355 - 60
Restriction endonuclease analysis of mitochondrial DNA from Candida parapsilosis and other Candida species; Su CS et al.; Mitochondrial DNA has been studied in a number of eukaryotic organisms . Differences in inter- and intraspecies mitochondrial DNA restriction patterns have been shown to be due to differences in nucleotide sequences and have been used to study evolutionary relationships and the mode of inheritance of the mitochondrial genome . A relatively rapid and efficient method for the extraction of mitochondrial DNA from Candida parapsilosis and other Candida species was developed . Zymolyase was used to induce yeast protoplasts and mitochondrial DNA was extracted from DNase I-treated mitochondrial preparations . Digestion with the restriction endonucleases Eco RI, Hind III and Bam HI yielded the most definitive restriction patterns . The results of the restriction endonuclease analysis were in agreement with the current identification of these organisms . Candida parapsilosis, Candida albicans and Candida kefyr showed different restriction patterns . Eight Candida parapsilosis strains were compared and all had identical fragment patterns . The molecular size was approximately 30 kilobase pairs and the GC content was 33.2% . The results of these experiments demonstrate the potential of a simple molecular technique for the differentiation of yeast species.

Yeast, 1989 Apr, 5 Spec No, S225 - 9
Isolation and chemical and biological characterization of antigenic mutants of Candida albicans serotype A; Miyakawa Y et al.; Candida albicans serotype A possesses a specific antigen designated antigenic factor 6, that resides in the mannans on the cell surface . To define the molecular structure of antigenic factor 6, as well as to determine the role of cell wall mannan in the ability of C . albicans to adhere to epithelial cells, we isolated antigenic factor 6-deficient mutants by screening with agglutinating monoclonal antibody (MAb) CA4-2 which corresponds to polyclonal antibody (PAb) factor 6 . 1H-NMR spectral analyses of the purified mannans from the parent and the mutants showed loss of the signal at 4.77 ppm, corresponding to the beta-linkage of the side chain, in the mutants . Although the parent whole mannan as well as its mannohexaose fragment (M6) inhibited the agglutination reaction between C . albicans serotype A cells and MAb CA4-2, the mutant mannan showed lower inhibitory activity and a decreased amount of M6 in its acetolyzed products . These results indicate that the mutant mannan is defective in the side chain of M6 which is bound, via beta-linkage, to a branch of the inner side chains, resulting in the loss of reactivity with MAb CA4-2 . Experiments on the adherence of C . albicans showed that the antigenic mutants as well as C . albicans serotype B strains, which lack antigenic factor 6, had significantly (p less than 0.01) less adherence ability than the parent strain . These results suggest that the side chains of M6 specific for C . albicans serotype A mannan are heavily involved in the adherence mechanisms as ligands.

J Antimicrob Chemother, 1989 Apr, 23(4), 557 - 64
The effect of pentamidine salts on the in-vitro responses of neutrophilic granulocytes; Arnott MA et al.; Therapeutic concentrations (0.3-1.5 mg/l) of pentamidine isethionate and pentamidine mesylate, obtained after parenteral administration of the drugs, did not influence neutrophilic granulocyte adherence, random and chemotactic migration or phagocytosis of Candida albicans spores in vitro . At concentrations of 0.7, 1.1 and 1.5 mg/l, the ability of neutrophilic granulocytes to kill C . albicans spores was depressed (P less than 0.001); at all concentrations used, their ability to reduce nitroblue tetrazolium was decreased (P less than 0.001) . There was no significant difference between the drugs with regard to these impairments in neutrophilic granulocyte function . It is likely that pentamidine salts inhibit superoxide radical formation in the stimulated neutrophilic granulocyte and that this dysfunction leads to depressed intracellular killing of C . albicans spores.

J Clin Microbiol, 1989 Apr, 27(4), 681 - 90
Switching of Candida albicans during successive episodes of recurrent vaginitis; Soll DR et al.; Strain relatedness and switching were monitored in Candida albicans strains isolated from different body locations through three episodes of recurrent vulvovaginal candidiasis separated by two treatment-latency periods in a single patient . Strain relatedness was assessed by comparing Southern blot hybridization patterns with the relatively immobile mid-repeat sequence Ca3 . The following conclusions are demonstrated . (i) Three different strains of C . albicans colonized the mouth, the area under the breasts, and the vulvovaginal, anal, and rectal regions, respectively, at the time of the first infection . (ii) The same strain of C . albicans was responsible for the three vaginal infections . (iii) Switching of colony phenotype occurred with each new vaginal infection . (iv) Enrichment of drug-resistant switch phenotypes (assessed in vitro) was unlikely the basis for the changes in the switch phenotypes of the strain found in the vulvovaginal, anal, and rectal areas after treatment of the first infection with clotrimazole . (v) The same strain of C . albicans was responsible for the recurrent increases in mouth colonization and was distinct from the recurrent vaginal strain . The results of this case study demonstrate the need for further detailed analyses of full-body mycofloras, strain relatedness, switching repertoires, and changes in drug susceptibility during successive episodes of recurrent vulvovaginal candidiasis.

Eur J Haematol, 1989 Apr, 42(4), 375 - 81
Biological properties in vitro of a combination of recombinant murine interleukin-3 and granulocyte-macrophage colony-stimulating factor; Riklis I et al.; The effect of recombinant murine interleukin-3 (rIL-3) and recombinant murine granulocyte-macrophage colony-stimulating factor (rGM-CSF) on in vitro murine myeloid progenitor cell (CFU-C) growth and on the function of murine resident peritoneal macrophages was investigated . Both rIL-3 and rGM-CSF are known to support the growth of CFU-C and, when combined, were found to act synergistically to induce the development of an increased number of CFU-C . The distribution pattern of myeloid colonies in the presence of these two growth factors was in general similar to that in the presence of rGM-CSF alone . Both rGM-CSF and rIL-3 enhanced the phagocytosis of Candida albicans (CA) by mature macrophages producing an increase in the percentage of phagocytosing cells as well as an increase in the number of yeast particles ingested per cell . No additive effect on the phagocytosis was observed when the two growth factors were added concurrently . rGM-CSF, but not rIL-3, enhanced the killing of CA by macrophages . This killing was inhibited by scavengers of oxygen radicals.

Ann Plast Surg, 1989 Apr, 22(4), 337 - 42
Adherence of microorganisms to breast prostheses: an in vitro study; Sanger JR et al.; The quantitative and morphological characteristics of microbial adherence of four organisms--Staphylococcus epidermidis, S . aureus, Escherichia coli and Candida albicans--to the surfaces of different breast prostheses were observed . Semiquantitative adherence studies based on a modification of Maki's roll culture technique even after short contact times showed (1) increased microbial adherence at higher concentrations of the organisms and (2) differences in adherence properties between gram-positive bacteria and other organisms tested, noted also at lower organism concentrations . Scanning electron microscopy (SEM) to identify microorganisms on foam-covered prostheses, however, revealed organisms in the interstitial spaces that were not recovered by the plating technique . Other features on SEM were extracellular "slime" produced by S . epidermidis, which appears to act as a cement by which bacteria are held against prosthetic surfaces . These in-vitro findings suggest that brief exposure of the prostheses to a few organisms, particularly gram-positive bacteria, at the time of implantation would be sufficient inoculum for bacterial adherence to prosthetic surfaces.

Endocrinology, 1989 Apr, 124(4), 1965 - 72
Characterization of an estrogen-binding protein in the yeast Candida albicans; Skowronski R et al.; An estrogen-binding protein (EBP) has been identified and characterized in the cytosol of the pathogenic yeast Candida albicans . Binding of {3H}estradiol was found to be optimal at pH 7.4 in the presence of 0.3 M KCl and was linearly related to protein concentration . Binding was very rapid, reaching maximal levels in about 30 min, and was reversible with a dissociation rate constant of 13.2 +/- 1.7 x 10(-4) sec-1 . EBP binding was destroyed by treatment with proteolytic enzymes and by high temperatures . Scatchard analysis of the {3H}estradiol equilibrium binding data of C . albicans (strain stn-1) yielded an apparent dissociation constant of 12.3 +/- 2.1 nM and a maximal binding capacity of 753 +/- 145 fmol/mg protein . Binding competition experiments showed very high specificity and stereoselectivity of EBP, demonstrating the following order of potency in displacing {3H}estradiol: 17 beta-estradiol greater than estrone greater than estriol greater than 17 alpha-estradiol . Negligible competitive potency was found for other mammalian steroid hormones, diethylstilbestrol, tamoxifen, or fungal hormones . The abundance of EBP was 4- to 10-fold higher during the early logarithmic growth phase of yeast cells than during the stationary phase . The molecular size of EBP, measured by Sephacryl S-200 gel exclusion chromatography, yielded a Stokes radius of approximately 29 A . Sucrose density gradient sedimentation showed a sedimentation coefficient (S2020,W) of 4, with no ionic dependent aggregation of the {3H}estradiol-EBP complex . The apparent mol wt of the EBP is approximately 46,000, with an axial ratio of 1, indicating the symmetrical shape of the molecule . In summary, in addition to the previously described corticosterone-binding protein, a separate high affinity, stereospecific, estrogen-selective binder has been demonstrated in the cytosol of C . albicans.

J Biol Regul Homeost Agents, 1989 Apr-Jun, 3(2), 71 - 8
Potential use of tuftsin in treatment of candida peritonitis in a murine model; Levy R et al.; A major complication of continuous ambulatory peritoneal dialysis (CAPD) is peritonitis caused by Candida albicans . Increasing the activity of the peritoneal macrophages, the predominant cell type found in the peritoneal cavity, may be a promising treatment for this infection . Tuftsin was found to increase thioglycollate-elicited mouse peritoneal macrophage activity . 2x10(-7) M tuftsin enhanced two-fold cell association with radiolabelled candida, superoxide aniom production, and killing activity . Thus, a model consisting of mice undergoing peritoneal dialysis was developed in order to study the use of tuftsin as a therapeutic drug against peritoneal candidiasis . Administration of tuftsin (50 micrograms/mouse) before candidiasis induction with a lethal dose of candida (7x10(8) candida per mouse) improved mouse survival up to 70%, compared with 10% in the control group . The potential of tuftsin as a treatment for candidiasis was shown when the infection was induced with a sublethal dose of candida . Daily intraperitoneal injections of tuftsin (50 micrograms) to the sublethally infected mice caused a significant decrease in the number of candida recovered from the peritoneal cavity and from the blood (from 700 +/- 190 to 110 +/- 26 CFU/ml and from 100 +/- 26 CFU/ml to 17 +/- 8 CFU/ml, respectively) . In addition, a larger number of peritoneal macrophages with greater phagocytic and killing activity were found in the tuftsin-treated mice . The effect of tuftsin may promote its potential use in the therapy of peritonitis in patients undergoing chronic peritoneal dialysis.

Rev Chir Oncol Radiol O R L Oftalmol Stomatol Ser Stomatol, 1989 Apr-Jun, 36(2), 91 - 8
{Apiphytotherapeutic original preparations in the treatment of chronic marginal parodontopathies . A clinical and microbiological study}; Gafar M et al.; The paper presents results obtained by the treatment of chronic marginal parodontopathies with natural products of apiarian derivatives and vegetal extracts . These are original preparations such as Proparodont, sage extracts, watercress extracts, etc., by comparison with other similar existing products, and with zinc chloride . The clinical study evaluated the "inflammation status of the marginal prodontium" on the basis of variations in the PMA index . The microbiological study has established the bacteriostatic and the bactericidal activities of the products employed . The results obtained stress the high antimicrobial activity of the original products called Proparodont, and stress its antimycotic effects, especially against Candida albicans . The blackwort (Symphytum off.) extracts have a good repair effect, especially after surgical procedures . The complex original products based on propolis and vegetal extracts are indicated in the treatment of inflammatory lesions of the gingivo-parodontal tissues, and of the buccal mucosa . They also have antimicrobial effects, as well as antimycotic, antiinflammatory and antiscar effects . They de not have side effects which are characteristic for other medicinal drugs employed in the treatment of chronic marginal parodontopathies.

Arch Intern Med, 1989 Apr, 149(4), 962 - 4
Candidal sinusitis and diabetic ketoacidosis . A brief report; Dooley DP et al.; A 55-year-old man presented with diabetic ketoacidosis and pansinusitis due to infection with Candida albicans . The infection responded to local drainage procedures, the administration of amphotericin B (2 g), and aggressive medical therapy of the ketoacidosis . Sinusitis due to C albicans is rare but may be more frequently seen in the immunocompromised host . Unlike those infections caused by Mucor or Aspergillus species, sinusitis due to C albicans may respond to local drainage and amphotericin B therapy.

Scand J Dent Res, 1989 Apr, 97(2), 178 - 85
Phenotypic characterization of mononuclear cells and class II antigen expression in angular cheilitis infected by Candida albicans or Staphylococcus aureus; Ohman SC et al.; In the present study we characterized the phenotypes of infiltrating mononuclear cells in angular cheilitis lesions to further explore the pathogenesis of this disorder . Frozen sections from lesions infected by Candida albicans and/or Staphylococcus aureus were subjected to immunohistochemical analysis utilizing monoclonal antibodies directed to subsets of T-lymphocytes, B-lymphocytes, and macrophages . In addition, the expression of Class II antigens (HLA-DP, -DQ, -DR), the interleukin 2- and transferrin-receptors was studied on resident and infiltrating cells . An intense infiltration of T-lymphocytes was accompanied by expression of Class II antigens on the epidermal keratinocytes in lesion infected by Candida albicans . The Staphylococcus aureus infected lesions displayed a diffuse infiltration of T-lymphocytes but virtually no expression of Class II antigen by epidermal keratinocytes . These observations suggest that the cell-mediated arm of the immune system is involved in the inflammatory reaction of lesions infected by Candida albicans . In addition, the present study confirms that epidermal expression of Class II antigens is closely related to the type and magnitude of the infiltrating T-lymphocyte . Finally, these findings indicate that the type of inflammatory reaction in angular cheilitis is primarily dependent on the isolated microorganism, although the clinical pictures of the disorder are virtually identical.

J Immunol, 1989 Mar 15, 142(6), 1874 - 80
HIV-induced immunodeficiency . Relatively preserved phytohemagglutinin as opposed to decreased pokeweed mitogen responses may be due to possibly preserved responses via CD2/phytohemagglutinin pathway; Hofmann B et al.; We studied the proliferative response of PBL to the mitogens PHA and PWM and Candida albicans Ag in 301 HIV seropositive homosexual men, of whom 55 had AIDS . The responses to PHA were reduced only in the clinically ill HIV seropositive subjects . In contrast, the responses to PWM were profoundly reduced in most HIV seropositive subjects including the asymptomatic group . Further analysis of 16 HIV seropositive subjects showed that the proliferative responses were reduced in both CD4 and CD8 T cell subsets . A total of 15 HIV seropositive individuals with low responses to PWM, of whom seven had AIDS and eight controls were chosen for the following studies . Expression of T3, Ti, delta receptors, and CD2 was investigated and showed an increased percentage of CD2 receptors positive cells in HIV seropositive subjects without AIDS . The proliferative responses of PBL to stimulation with PHA, PWM, antibodies to CD3, or antibodies to CD2 were investigated and showed significant correlation in controls, whereas in contrast, only the responses to PHA and CD2ab correlated in patients with AIDS . The proliferative responses to CD2ab and CD3ab in controls were larger than the responses to both PHA and PWM . In patients, these responses were less suppressed than the responses to PWM indicating that stimulation with mitogens is more complex than a simple stimulation of Ti/T3 and CD2 receptors . Further investigations were done on resting T cells, i.e., lymphocytes depleted of macrophages and pre-activated cells . Addition of PHA to these cells resulted in preactivation with expression of IL-2R (CD25) but not in proliferation . In contrast, addition of PHA plus SRBC, which bind to the CD2 receptors caused IL-2R expression, IL-2 production, and proliferation . Addition of PWM + SRBC did not result in proliferation . A comparison of the responses to PHA + SRBC of resting T cells from 26 HIV seropositive individuals, of whom seven had AIDS and 12 seronegative controls, showed that these responses were normal or only slightly decreased in the 19 seropositive men without AIDS whereas it was decreased in AIDS patients . Nevertheless, all AIDS patients showed clear-cut responses in this assay . Thus, the discrepancy between responses to PHA and PWM may be explained by an at least partially preserved function of the PHA/CD2-dependent pathway . We suggest that the defect induced by the HIV infection primarily concerns T3/Ti-induced responses.

Infect Immun, 1989 Mar, 57(3), 693 - 700
Mannan as an antigen in cell-mediated immunity (CMI) assays and as a modulator of mannan-specific CMI; Domer JE et al.; Mannan (MAN) extracted from Candida albicans 20A was investigated for its potential as an antigen in the detection of cell-mediated immunity (CMI) in vivo and in vitro and for its ability to modulate CMI when administered intravenously (i.v.) . CBA/J mice were either immunized as adults by the cutaneous inoculation of 10(6) viable blastoconidia or colonized as infants (primed) and then boosted cutaneously as adults . When immunized animals were footpad tested with MAN, highly significant delayed-type hypersensitivity (DH) responses were detected . The DH responses to MAN were of a greater magnitude than those noted with the same quantity of cell wall glycoprotein (GP), an ethylenediamine extract of the cell wall which contains both glucan and MAN . In contrast, GP was a better antigen for the detection of CMI responses in an in vitro lymphoproliferative assay with either spleen or lymph node cell suspensions . Mice treated with MAN i.v . prior to the initiation of immunization or between priming and secondary inoculations developed significantly suppressed DH reactions when tested with either MAN or GP . The lowest effective dose of MAN was 250 micrograms, maximum suppression occurred with 500 micrograms, and either dose given 1 week prior to immunization was suppressive . The suppression by MAN was specific for MAN or the MAN-containing GP . Responses to another unrelated candidal antigen, a membrane extract designated BEX, were relatively unaffected . MAN, therefore, was an effective antigen for the detection of CMI in vivo, and its administration i.v . created what appeared to be a MAN-specific suppression since it could be detected with both MAN and a MAN-containing extract from the cell wall . Caution must be exercised in the interpretation of these data, however, since the protein component of each of these extracts has not been characterized with respect to its potential role in the phenomena observed.

J Nucl Med, 1989 Mar, 30(3), 385 - 9
Radiolabeled, nonspecific, polyclonal human immunoglobulin in the detection of focal inflammation by scintigraphy: comparison with gallium-67 citrate and technetium-99m-labeled albumin; Rubin RH et al.; The accumulation of nonspecific polyclonal human immunoglobulin (IgG) radiolabeled with 125I or 111In was compared to that of {67Ga}citrate and {99mTc}albumin in rats with deep thigh inflammation due to Escherichia coli infection . Serial scintigrams were acquired at 1, 3, 24, and in some cases, 48 hr after injection . As early as 3 hr postinjection, {111In}IgG showed greater accumulation at the lesion than {99mTc}HSA (p less than 0.01) . Both {125I}IgG and {111In}IgG showed greater accumulation than {67Ga}citrate (p less than 0.01) . At 24 hr, IgG image definition increased, while HSA image definition decreased, and the intensity of accumulation of both IgG preparations was greater than that of {67Ga}citrate or {99mTc}HSA (p less than 0.01) . At all imaging times, {67Ga}citrate accumulation was surprisingly low . In inflammation produced by Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, or turpentine, {111In}IgG accumulation was similar to the results obtained with Escherichia coli . These studies suggest that focal sites of inflammation can be detected with radiolabeled nonspecific human polyclonal IgG.

Cah Anesthesiol, 1989 Mar-Apr, 37(2), 77 - 87
{Antibiotic prophylaxis using a combination of pefloxacin and fosfomycin in heart surgery with CEC (extracorporeal circulation) in patients allergic to beta-lactams}; Lebreton P et al.; This study conducted for 15 months, was carried out in 34 patients with beta-lactam allergy scheduled for open heart surgery . In the study, pefloxacin was given orally an hour before the induction of anaesthesia and then as a short infusion following induction . When the bypass was stopped, pefloxacin (400 mg) and fosfomycin (60 mg.kg-1) were given in association by two separate slow intravenous infusions just before sternal closure and repeated in intensive care unit postoperatively . The antibiotic kinetics was observed in blood and cellular concentrations (atria, sternum and mediastinal part of pleura) . The antibiotic level analysis showed a good diffusion during the surgical procedure, particularly during the bypass . The pefloxacin given orally was found to achieve satisfactory plasma levels of 5.4 to 6.9 mg.l-1 during sternotomy and always higher than 3 mg.l-1 during bypass . At the sternal closure, the residual plasma level was about 2.8 mg.l-1 before the reinfusion . The kinetic evaluation of fosfomycin has also shown same effective levels . Hence, the clinical potency of these antibiotics was confirmed as predicted by their excellent tissue diffusion . Thus, clinical evaluation was in favour of this antibiotic-association in most cases, except the two following ones . The first case had a lethal bronchiolar and lung reinfection with Pseudomonas aeruginosa and Candida albicans germs which appeared at the 6th postoperative day . The second patient is a case of antibiotic prophylaxis failure . He had developed an acute suppurating mediastinal infection at the seventh postoperative day with a methicillin resistant Staphylococcus aureus which had become pefloxacin fosfomycin resistant . However, the evolution was ultimately good after surgical disinfection of sternotomy and 30 days of drainage and irrigation with antiseptic solution associated with well adapted antibiotic treatment: vancomycin, pristinamycin and rifamycin . In fact, the choice of pefloxacin and fosfomycin for prophylaxis against staphylococcus in cardiac surgery is the right choice for patients having beta-lactam allergy . Their spectral activity and pharmacokinetics give us satisfactory results . But it is not the absolute solution as the bacteria responsible for nosocomial infection (hospital borne infection) may be found resistant to this association.

J Dent Assoc S Afr, 1989 Mar, Suppl 1, 6 - 10
The causation of oral precancer and cancer; Altini M et al.; Most cases of oral cancer result from the action of exogenic carcinogenic agents, some of which act synergistically in producing their effects . The evidence implicating tobacco and alcohol abuse is overwhelming and cannot be refuted . Other clearly identifiable aetiological agents include betel nut chewing and excessive exposure to sunlight . While there is increasing evidence of a viral causation, this is not yet clearly established . Similarly, the role of Candida albicans remains uncertain . Lichen planus and discoid lupus erythematosus may constitute important predisposing conditions, but the documentation remains inadequate and inconclusive, as does that implicating electrogalvanism . Tertiary syphilis is no longer considered a significant factor in oral cancer . Sideropenic dysphagia and haemoglobin and serum iron deficiencies may be of importance in the development of oral carcinoma, particularly in elderly women with no history of tobacco and alcohol abuse . The roles of poor oral hygiene and sharp edges of teeth and dentures have probably been overemphasized in the past.

Clin Exp Allergy, 1989 Mar, 19(2), 191 - 5
Allergenic components of Candida albicans identified by immunoblot analysis; Shen HD et al.; Allergenic components of Candida albicans fractionated by SDS-polyacrylamide gel electrophoresis (PAGE) and transferred to nitrocellulose membranes were identified using sera from 30 asthmatic patients who showed positive skin test and RAST (radio-allergosorbent test) to C . albicans . The IgE-binding yeast components in the complex antigen preparation were then detected by reaction with enzyme-labelled anti-human IgE antibodies . They were confirmed by Coomassie blue R-250 staining of the membrane to visualize all protein bands after reaction with the enzyme substrate . The IgE-binding patterns of the sera tested were heterogeneous, displaying a total of 16 identifiable components with molecular weights ranging from 20 to 94 kD . A 40 kD component showed the highest IgE-binding frequency, being recognized by 23 (77%) of the 30 sera examined . The other 15 allergenic components identified were recognized by less than 25% of the sera tested . Only two of the 30 serum samples contained IgE antibodies reactive with seven to eight allergenic components . Ten of the 30 sera reacted with only one allergenic component, and the remaining serum samples recognized two to five of the 16 identified allergens . Results described in this study are applicable to allergen standardization work and provide a basis for further study on the role of C . albicans in clinical allergy.

Mycoses, 1989 Mar, 32(3), 119 - 22
Infection of human fetal membranes in vitro with Candida albicans; Hayashi S et al.; The present study was designed to examine whether C . albicans could infect and penetrate through intact human fetal membranes in vitro . Fragments of fresh fetal membranes were obtained from pregnant women undergoing a cesarean section . C . albicans was inoculated onto the surface of the maternal side of the membranes, after which the inoculated tissue were incubated at 31 degrees C . C . albicans was able to infect and penetrate through the membranes into the fetal side within 24 h of incubation.

Can J Microbiol, 1989 Mar, 35(3), 349 - 58
Ultrastructural study of galacturonic acid distribution in some pathogenic fungi using gold-complexed Aplysia depilans gonad lectin; Benhamou N; Aplysia gonad lectin, isolated from the mollusc Aplysia depilans, was successfully conjugated to colloidal gold and used for ultrastructural detection of galacturonic acids in some pathogenic fungi . These sugar residues were found to occur in the fibrillar sheath surrounding hyphal cells of Ascocalyx abietina and in intravacuolar dense inclusions of this fungus spores . In hyphae and spores of Ophiostoma ulmi, galacturonic acids were detected mainly in the outermost wall layers . In contrast, these saccharides appeared associated with the innermost wall layers and especially the plasma membrane of Verticillium albo-atrum cells . Galacturonic acids were found to be absent in cells of Fusarium oxysporum f.sp . radicis-lycopersici and Candida albicans . These cytochemical data indicate therefore that a heterogeneity in wall composition exists between ascomycete fungi . The significance of the presence of galacturonic acids in the cell walls of certain fungi is still open to question.

Antimicrob Agents Chemother, 1989 Mar, 33(3), 362 - 8
Tissue concentrations and bioactivity of amphotericin B in cancer patients treated with amphotericin B-deoxycholate; Collette N et al.; We have studied amphotericin B concentrations in tissues of 13 cancer patients who died after having received 75 to 1,110 mg (total dose) of amphotericin B-deoxycholate for suspected or proven disseminated fungal infection . Amphotericin B concentrations were measured by high-pressure liquid chromatography (HPLC) and by bioassay, the latter being done on tissue homogenates as well as on tissue methanolic extracts . The fungistatic and fungicidal titers of the tissue homogenates were also tested against three strains of Candida albicans and one strain of Aspergillus fumigatus . Tissue concentrations of amphotericin B measured by HPLC varied with the tested tissues as well as with the total dose of amphotericin B-deoxycholate administered and ranged from 0.4 to 147.1 micrograms/g . A mean of 38.3% (range, 23.0 to 51.3%) of the total dose was recovered by HPLC from all of the tested organs . Bioassay of tissue methanolic extracts reached 58 to 81% of the concentration measured by HPLC, whereas only 15 to 41% was recovered from the homogenates . Overall, 27.5% of the total dose was recovered from the liver, 5.2% was recovered from the spleen, 3.2% was recovered from the lungs, and 1.5% was recovered from the kidneys . The median concentration in bile was 7.3 micrograms/ml, suggesting that biliary excretion could contribute to amphotericin B elimination to an estimated range of 0.8 to 14.6% of the daily dose . Fungicidal titers were seldom measured in tissues, but fungistatic titers were observed and were linearly correlated with amphotericin B concentration measured by HPLC . In conclusion, only a small proportion of the amphotericin B administered as amphotericin B-deoxycholate to patients seems diffusible and bioactive.

J Ultrasound Med, 1989 Mar, 8(3), 121 - 4
Sonography of Candida albicans cystitis; Gooding GA; Candida albicans infections are opportunistic and range from asymptomatic infections to life-threatening ones . Noted on sonography in three proven cases, Candida albicans cystitis produced a mildly thickened bladder wall and a discrete, well-defined, dense fluid-fluid interface within the bladder, debris that contained the long threadlike pseudomycelia of the fungus . This fluid-fluid interface shifted with changes in position . The sonographic appearance, although not pathognomonic, was similar in all three cases . Sonography was used to monitor the progress of therapy . In all three cases, conservative treatment successfully cleared the vesical debris without significant sequelae or the formation of concretions analogous to bezoars and the bladder returned to normal except for minimal residual wall thickening.

Radiobiologiia, 1989 Mar-Apr, 29(2), 230 - 4
{Effect of He-Ne laser radiation on the chemiluminescence of mouse spleen cells}; Karu TI et al.; A study was made of He-Ne laser radiation (lambda = 632.8 nm) on spontaneous chemiluminescence of mouse splenic cells and that stimulated by addition of Candida albicans . Irradiation with low-intensity red light was shown to stimulate cell chemiluminescence and to intensify that stimulated by C . albicans within the dose range from 100 to 300 J/m2 with a maximum at about 200 J/m2.

J Burn Care Rehabil, 1989 Mar-Apr, 10(2), 138 - 45
Effect of thermal injury and immunosuppression on the dissemination of Candida albicans from the mouse gastrointestinal tract; Ekenna O et al.; Candida albicans dissemination through the gastrointestinal tract was examined in mice given a thermal injury, immunosuppressive therapy, or both . After gastrointestinal tract colonization with C . albicans, mice were initially subjected to a 20% total body surface area, full-thickness, dorsal scald burn . Only one mouse in the burned group (5%) had evidence of C . albicans in the liver at the time the mice were killed . No dissemination was observed in sham-burned animals . When mice were immunosuppressed with cyclophosphamide, an increased incidence of gastrointestinal tract dissemination was noted in burned (31%) and sham-burned (23%) mice; however, only 3 days after burn was there a significant difference in dissemination between burned and sham-burned mice (p less than 0.02) . This corresponded to the day of severest neutropenia in response to cyclophosphamide treatment . The results of the study indicate that C . albicans can disseminate from the gastrointestinal tract in response to thermal injury, but a significant suppression of the immune response must occur for the event to be commonplace.

Rev Infect Dis, 1989 Mar-Apr, 11(2), 310 - 5
Diagnostic value of serum antibody and antigen detection in heroin addicts with systemic candidiasis; Bisbe J et al.; The diagnostic value of antibody detection by indirect hemagglutination (IHA), indirect immunofluorescence (IFA), and counterimmunoelectrophoresis (CIE) and of Candida albicans mannan antigen detection by latex agglutination was studied in 36 cases of systemic candidiasis in heroin addicts . The IHA and IFA techniques were highly sensitive (97% and 91%, respectively), but their specificity was low (60% and 50%) . When a titer of greater than or equal to 1:2,560 was used as a criterion for IHA positivity, the specificity of the test rose to 87%, with sensitivity at 75% . CIE had a high degree of specificity (96%) but a low degree of sensitivity (58%) . A good correlation was found between clinical evolution of infection and serologic data . Two of 12 patients who could be followed for 9-16 months had a rise in antibody titer detected either by IFA or by IHA and CIE . These two patients had a persistent chondrocostal tumor and C . albicans endocarditis, respectively . All of the other patients, who were cured, had a decrease in titer detected by IHA and IFA and had negative CIE results at the end of follow-up . Serum mannan antigen was not found in any case . The detection of antibody to C . albicans may be useful for diagnosis and follow-up of such patients.

Oral Surg Oral Med Oral Pathol, 1989 Mar, 67(3), 279 - 81
Effect of nystatin and chlorhexidine digluconate on Candida albicans; Barkvoll P et al.; Polyene antibiotics such as nystatin and amphotericin B are among the most widely recommended drugs for use against oral candidiasis . It is also generally accepted that chlorhexidine gluconate is an appropriate adjunct or an alternative to specific antimycotic drugs . The aim of the present study was to examine the effect of the combination of nystatin and chlorhexidine digluconate on Candida albicans in vitro . The minimum inhibitory concentration (MIC) value for the combination of the two drugs was found to be significantly higher than the values for each of the drugs alone, approximately 33 times the MIC value for the nystatin solution and 4 times the value for chlorhexidine digluconate . The results of the MIC study and the presence of a precipitate in all combinations of nystatin and chlorhexidine digluconate showed that the combination of the drugs is not effective in vitro against Candida albicans . The most likely reason is that a low solubility chlorhexidine-nystatin salt is formed, thus rendering the combined drug complex ineffective as an antibiotic agent.

J Med Microbiol, 1989 Mar, 28(3), 223 - 5
Antibodies against Trichosporon beigelii in vaginal washings from asymptomatic women; Quindos G et al.; Trichosporon beigelii was isolated from vaginal washings from three asymptomatic women . All three women had IgG or IgA anti-T . beigelii antibody titres greater than or equal to 20 when tested by an indirect immunofluorescence assay against the three strains isolated . Titres greater than or equal to 160 were found when each patient was tested against her own isolate . Patients with Candida albicans vulvovaginitis, or from whom C . albicans or Toruloposis glabrata was isolated from vaginal washings, or who had negative cultures for yeasts, had titres less than or equal to 20.

J Bacteriol, 1989 Mar, 171(3), 1372 - 8
Cloning, purification, and properties of Candida albicans thymidylate synthase; Singer SC et al.; The thymidylate synthase (TS) gene was isolated from a genomic Candida albicans library by functional complementation of a Saccharomyces cerevisiae strain deficient in TS . The gene was localized on a 4-kilobase HindIII DNA fragment and was shown to be expressed in a Thy- strain of Escherichia coli . The nucleotide sequence of the TS gene predicted a protein of 315 amino acids with a molecular weight of 36,027 . The gene was cloned into a T7 expression vector in E . coli, allowing purification of large amounts of C . albicans TS . It was also purified from a wild-type C . albicans strain . Comparison of several enzyme properties including analysis of amino-terminal amino acid sequences showed the native and cloned C . albicans TS to be the same.

Zhonghua Ya Yi Xue Hui Za Zhi, 1989 Mar, 8(1), 1 - 5
{AIDS and the oral cavity}; Hwang KC et al.; The oral cavity is the site for a number of diseases associated with an infection of the human immunodeficiency virus . Often the oral lesions may appear before the establishment of an AIDS diagnosis; and occasionally, the diagnosis may depend solely on the oral manifestations . The most commonly reported oral infections are those caused by Candida albicans and the herpes simplex virus . Hairy leukoplakia, a newly described lesion, may also be of viral origin . Kaposi's sarcoma is the most frequently reported oral malignancy in patients with AIDS . Oral squamous cell carcinoma and non-Hodgkin's lymphomas have also been reported.

J Infect Dis, 1989 Mar, 159(3), 488 - 94
The use of a DNA probe for epidemiological studies of candidiasis in immunocompromised hosts; Fox BC et al.; Reproducible typing procedures to differentiate isolates of Candida albicans are limited . C . albicans isolates were obtained from immunocompromised patients by using DNA restriction enzyme fragment analysis and hybridization with both a radiolabeled mitochondrial DNA probe and a nonradioactive (biotinylated) DNA probe . There were 110 pathogenic and nonpathogenic C . albicans isolates from 63 immunocompromised patients . EcoRI restriction fragment analysis with the biotinylated probe revealed different "fingerprint" patterns for 60 of 63 patients . Analysis of 57 isolates from 20 patients showed no intrapatient variation regardless of the isolation site . DNA probe "fingerprint" patterns were analyzed for eight patients on serially recovered (range, 2-18 mo) C . albicans isolates . The unique patient profiles persisted over time . The application of this biotinylated C . albicans DNA probe provides a more sensitive means than simple gel restriction fragment analysis to define the epidemiology of C . albicans infection . The use of this biotin-labeled nonradioactive probe has potential application in clinical evaluations of outbreaks of nosocomial candidiasis.

Steroids, 1989 Mar-May, 53(3-5), 567 - 78
Membrane fluidity alterations in a cytochrome P-450-deficient mutant of Candida albicans; Lees ND et al.; A cytochrome P450-deficient mutant of the pathogenic fungus, Candida albicans, which accumulates exclusively 14 alpha-methylsterols in place of the normal end product sterol, ergosterol, was examined for alterations in membrane fluidity by electron paramagnetic resonance . The results using four nitroxyl spin labels indicated that exponential phase cultures of the mutant strain, D10, had a uniformly more rigid membrane than similarly grown wild type . Since D10 shows a sterol spectrum similar to that of wild type cells treated with imidazole and triazole antifungal agents, many of the physiological effects reported as the result of azole application may be the result of alterations in membrane fluidity.

Hua Xi Yi Ke Da Xue Xue Bao, 1989 Mar, 20(1), 39 - 41
{In vitro assessment of candidacidal activity of human leukocyte myeloperoxidase preparation}; Li CL et al.; Myeloperoxidase (MPO), present in the azurophilic granules of human polymorphonuclear neutrophils, is important in the oxygen-dependent microbicidal activity of neutrophils . The purpose of our study was to investigate the therapeutic potency of the MPO preparations . This paper is to present our primary work on MPO isolation and its microbicidal activity assay . White blood cells, isolated freshly from normal donors, were lysed with cetyltrimehylammonium bromide to liberate myeloperoxidase . The enzyme preparation was partially purified by 50% (NH4)2SO4 precipitation followed by 65% (NH4)2SO4 precipitation . A hundred million leukocytes yielded 1.03 mg protein of the MPO preparation with the RZ of 0.31 . The specific activity of the MPO preparation was about 29.25 u/mg . When 0.672 units of the MPO preparation were incubated with about 10(7) clinical isolates of Candida albicans in the presence of 0.2 mmol/L H2O2 and 0.14 mol/L NaCl . It was detected that 95.58 +/- 0.64% of the organisms were killed in the methylene blue staining system.

Pediatr Res, 1989 Mar, 25(3), 276 - 9
Defective leukocyte fungicidal activity in end-organ resistance to 1,25-dihydroxyvitamin D; Etzioni A et al.; Recent studies have shown 1,25(OH)2D3 receptor-mediated modulation of leukocyte proliferation, differentiation, and function . We examined the phagocytosis and killing of microorganisms by neutrophils and monocytes from five patients of three families with hereditary resistance to 1,25(OH)2D3 . Phagocytosis of microorganisms by patients' neutrophils and monocytes was normal . However, defective neutrophil killing activity toward Candida albicans (30-40% of controls) was found in all patients . The killing of Staphylococcus aureus was normal . The neutrophil chemiluminescence, nitroblue tetrazolium (NBT) dye reduction, and the generation of superoxide ions and hydrogen peroxide by neutrophils and monocytes after induction by either soluble stimuli or zymozan particles, did not differ from those in controls . The neutrophil myeloperoxidase activity was also normal . Monocytes obtained from two patients of different families before long-term calcium infusion therapy and after they became normocalcemic, demonstrated a similar impaired fungicidal activity toward Saccharomyces cerevisiae, indicating that hypocalcemia itself was not the cause of the killing defect . However, the addition of the Ca+2 ionophore A23187 (1 microM) to the test medium restored the monocyte fungicidal activity to normal . As patients' neutrophil cytosolic free calcium concentration was similar to that in controls, it is suggested that 1,25-(OH)2D3 exerts its effect on leukocyte function by a putative receptor-mediated regulation of subcellular calcium localization which may be important for fungicidal activity.

Blood, 1989 Mar, 73(4), 1045 - 9
Candidacidal activity of the neutrophil myeloperoxidase system can be protected from excess hydrogen peroxide by the presence of ammonium ion; Beilke MA et al.; Excessive concentrations of hydrogen peroxide inhibit the neutrophil myeloperoxidase system, presumably by inactivating the hypochlorous acid produced by this system . Ammonium ion generated by neutrophils and other cells can react with hypochlorous acid to produce monochloramine, an oxidant with good microbicidal activity, but relative resistance to inactivation by other compounds . In an assay based on the oxidation of 5-thio-2-nitrobenzoic acid, hydrogen peroxide reacted more readily with sodium hypochlorite (used as a source of hypochlorous acid) than with monochloramine . Also, in this assay Candida albicans yeast inactivated the oxidant activity of hypochlorous acid more completely than they did that of monochloramine . The killing of Candida by sodium hypochlorite, as determined in a standard colony count microbicidal assay, was inhibited by equimolar and greater concentrations of hydrogen peroxide; killing of this organism by monochloramine was not affected by a tenfold excess concentration of hydrogen peroxide . In microbicidal assays using 4 mU of myeloperoxidase and optimal or excessive concentrations of hydrogen peroxide or glucose and glucose oxidase to generate hydrogen peroxide, the excessive concentrations inhibited killing of Candida, but not Staphylococcus aureus . The inhibition of Candida killing could be reversed by addition of ammonium ion to convert hypochlorous acid to monochloramine . These results indicate that for certain organisms such as C albicans, conversion of hypochlorous acid to monochloramine by reactions with ammonium ion may extend the range of hydrogen peroxide concentrations under which killing by the myeloperoxidase system can occur by protecting the necessary microbicidal oxidants from inactivation by excess hydrogen peroxide.

Infect Immun, 1989 Mar, 57(3), 689 - 92
Natural inhibitor from Candida albicans blocks release of azurophil and specific granule contents by chemotactic peptide-stimulated human neutrophils; Smail EH et al.; A product released by Candida albicans hyphae which was previously determined to block the neutrophil respiratory burst also inhibited the degranulation response elicited by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) . When neutrophils were incubated with 100 micrograms of this Candida hyphal inhibitory product (CHIP) per ml and stimulated with 1,000 nM FMLP, release of the azurophil granule marker beta-glucuronidase and the specific granule marker lactoferrin was decreased to 31.2 +/- 5.7 and 35.7 +/- 5.3% of control, respectively . Inhibition was concentration dependent, with a half-maximal reduction of beta-glucuronidase and lactoferrin release being induced by 4 and 1 micrograms of CHIP per ml, respectively . In contrast to these striking alterations in response to FMLP, CHIP had no significant effect on lactoferrin release stimulated by phorbol myristate acetate . Moreover, actin polymerization, which has been suggested to be involved in regulation of degranulation, was unaffected by CHIP whether the neutrophils were stimulated by FMLP or phorbol myristate acetate . The selectivity of inhibition of neutrophil degranulation thus provides additional confirmation that CHIP is a useful agent for exploring human neutrophil activation pathways.

Arch Dermatol, 1989 Mar, 125(3), 357 - 61
Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus; Coldiron BM et al.; We examined 100 serial patients who were receiving care in a county outpatient immunodeficiency clinic and whose serum was positive by Western blot test for the human immunodeficiency virus (HIV) . Skin disorders were found in 92% of these HIV-infected patients, with little difference in prevalence or severity in three clinical categories: patients with the acquired immunodeficiency syndrome, patients with acquired immunodeficiency syndrome-related complex, and those who were asymptomatic . Patients positive for HIV antibodies had significantly more skin disease, with the exception of dermatophytosis, than did a historical control population . A strong association was observed between the use of zidovudine and the absence of infection with Candida albicans . We conclude that there is a high prevalence of skin disease in HIV-positive patients who seek medical care, and that specialists in skin disease should be included in these patients' initial evaluation and continuing care.

BMJ, 1989 Feb 11, 298(6670), 354 - 7
Assessment of DNA fingerprinting for rapid identification of outbreaks of systemic candidiasis; Matthews R et al.; DNA fingerprinting was assessed as an improved typing system for Candida albicans aimed at speeding the implementation of cross infection control measures in outbreaks of systemic candidiasis . The study was carried out with 45 previously characterised isolates from five different outbreaks and with 96 unrelated isolates from a mixed control population . Sixteen different genotypes were produced . Results were obtainable within days, reproducibility was high, and there was good discrimination among different outbreaks . Compared with existing typing systems DNA fingerprinting provides a robust system that may be used rapidly to identify outbreaks of nosocomial candidiasis in laboratories with no specialist skill in typing C albicans.

JAMA, 1989 Feb 10, 261(6), 878 - 83
Efficacy of an attachable subcutaneous cuff for the prevention of intravascular catheter-related infection . A randomized, controlled trial; Flowers RH 3rd et al.; We performed a randomized controlled trial of an attachable subcutaneous cuff for the prevention of central vascular catheter-related infection among patients receiving intensive care . Catheters were placed percutaneously into new sites with or without a cuff and were dressed with polyantibiotic ointment containing polymyxin, neomycin, and bacitracin . Microbial colonization developed in 34.5% of 29 control and 7.7% of 26 cuffed catheters . Catheter-related bloodstream infection occurred with 13.8% of control vs 0% of cuffed catheters . The cuff was not associated with adverse effects . An unexpectedly large proportion (75%) of catheter infections were due to Candida albicans . This may have been due, in part, to the use of polyantibiotic ointment, as suggested by a pooled analysis of previous trials that demonstrated increased Candida colonization of catheters with the ointment, which is not fungicidal . These data suggest that the cuff can reduce the incidence of catheter-related infection among high-risk patients receiving catheter site care with an antibacterial ointment.

Postgrad Med J, 1989 Feb, 65(760), 83 - 5
Hypersplenism due to fungal infection of spleen in a successfully treated patient with Hodgkin's disease; Raina V et al.; A 58 year old woman, with dermatitis herpetiformis was found to have Hodgkin's disease following the discovery of an abdominal mass and splenomegaly . Combination chemotherapy was given . Although the abdominal mass and systemic symptoms resolved, the splenomegaly did not and the patient developed severe prolonged anaemia and pancytopaenia . Splenectomy resulted in a complete reversal of the haematological abnormalities . Histopathological examination of the spleen revealed fungal granulomas of Candida albicans . No residual Hodgkin's disease was found . The patient thus had hypersplenism due to fungal granulomas in the spleen . This form of presentation of fungal granuloma is very rare and resulted in delay in diagnosis and considerable morbidity to the patient.

J Gen Microbiol, 1989 Feb, 135 ( Pt 2), 425 - 34
High frequency variation of colony morphology and chromosome reorganization in the pathogenic yeast Candida albicans; Suzuki T et al.; A clinical isolate of the pathogenic yeast Candida albicans varied in its colony morphology from smooth (o-smooth) to semi-rough type (SRT) and concomitantly lost its virulence for mice . In terms of DNA content, the smooth parent was near triploid when Saccharomyces cerevisiae strains of known ploidy were used as references . The SRT variant showed several features characteristic of polyploidy . From the SRT variant, revertant-like smooth (r-smooth) variants with recovered virulence were derived at a frequency of 5 x 10(-3) . The results of pulsed-field gel electrophoresis on chromosomal DNA showed changes in patterns of chromosome-sized DNA bands in the SRT variant as well as in r-smooth variants, which correlated with these variations . Correlations between colony morphology, state of ploidy and virulence of this asporogenous yeast are considered.

Pneumonol Pol, 1989 Feb, 57(2), 104 - 13
{Further studies on the occurrence of mycoses in the bronchial stump and bronchial anastomosis or trachea}; Zajaczkowska J et al.; In the years 1980-1985 sutures were removed endoscopically from stumps and anastomoses in 52 patients operated in the years 1969-1985 . The total number of bronchoscopies was 154, in 88 protruding threads into the airway lumen were removed . Interval between removal of first suture and date of surgery ranged from 0.5 to 192 months . Mycotic infection was diagnosed in 5 cases (9.6%) . The causative agents being Aspergillus fumigatus and Candida albicans . In all cases removal of protruding threads lead to a complete cure . It was found that incidence of such mycotic infections decreased from 20.2% observed during the years 1962-1979 to 9.6% in the years 1980-1985.

Res Microbiol, 1989 Feb, 140(2), 95 - 105
Effects of subinhibitory dose of amphotericin B on cell wall biosynthesis in Candida albicans; Mpona-Minga M et al.; Subinhibitory doses of amphotericin B in the culture medium of Candida albicans modified yeast cell wall synthesis . Analysis of isolated cell walls showed a decrease in mannose and an increase in amino acid and glucosamine levels . After fractionation of the cell wall by ethylenediamine or pronase digestion, study of the fractions corroborated an outer phosphopeptidomannan decrease and an enrichment of matrix constituents . Determination of the amount of chitin showed stimulation of synthesis of this amino polysaccharide in yeasts grown in the presence of amphotericin B . Decrease in phosphopeptidomannans and high production of other cell wall constituents are probably consequences of modification of the lipidic environment of membrane-bound enzymes by the antifungal polyene action.

Riv Eur Sci Med Farmacol, 1989 Feb, 11(1), 17 - 20
{Recent advances in Candida albicans mycoses in children}; Cantani A et al.; Infections with fungi appear to be increasing in frequency . Children who are debilitated, or are receiving prolonged steroid therapy or long-term antibiotic therapy are particularly susceptible to fungal infections . C . albicans causes infections of various organs . It may also form granulomas and produce a disseminated disease . In this paper the clinical manifestations, diagnosis and treatment of candidiasis are discussed.

Indian J Biochem Biophys, 1989 Feb, 26(1), 30 - 3
Influence of lipid composition on the sensitivity of Candida albicans to antifungal agents; Mago N et al.; Cerulenin, a specific inhibitor of fatty acid and sterol biosyntheses, inhibited growth and lipid synthesis in C . albicans, which on supplementing the growth medium with optimum concentrations of fatty acids was reversed . Significant changes in the levels of phospholipids and sterols were observed in fatty acid-supplemented cells . Altered phospholipids and their fatty acid profile rendered cells more resistant to miconazole and thereby more permeable to {3H}proline . Thus it appears that fatty acid composition plays an important role in determining the permeability susceptibility of C . albicans to drugs.

Can J Microbiol, 1989 Feb, 35(2), 260 - 4
Conditions affecting the amphotericin B mediated inhibition of Candida albicans attachment to cell cultures; Merkel GJ et al.; Sublethal amounts of amphotericin B inhibited the attachment of Candida albicans to cultured mammalian cells . The extent of inhibition was influenced by the concentration of serum and the growth phase of the yeasts used to inoculate the cell cultures . Yeasts which were in their exponential phase of growth or had formed germ tubes were the most sensitive to amphotericin B . Equivalent amounts of amphotericin B inhibited yeast-mammalian cell interactions to different degrees depending upon the culture's tissue origin.

Can J Microbiol, 1989 Feb, 35(2), 255 - 9
The effects of amphotericin B on the interaction of Candida albicans with fibroblast cultures; Merkel GJ et al.; Sublethal amounts of amphotericin B inhibited the interaction of Candida albicans with cultured fibroblasts . Different C . albicans clinical isolates exhibited varying degrees of sensitivity to the drug, but those isolates that were the most infective in control cultures appeared to be the most resistant to amphotericin B mediated infection inhibition . Although amphotericin B inhibited germ tube formation at the sublethal concentration of 0.3 microgram/mL, lower concentrations inhibited infection without preventing germination . The extent of this latter activity varied with the isolate and amphotericin B concentration and appeared to be related to sublethal effects on germinated yeasts . While amphotericin B effectively prevented new fibroblast infection, it did not dissociate those yeasts which had established an infection before its addition.

Arzneimittelforschung, 1989 Feb, 39(2), 230 - 3
Ultrastructural findings of Candida albicans blastoconidia submitted to the action of fenticonazole; Costa A et al.; A study has been conducted about ultrastructural changes induced by an imidazole derivative, fenticonazole (Lomexin), on Candida albicans blastoconidia . The structural upset has been progressively exerted starting from coating membrane surfaces throughout cytosol components and nuclear compart, so that the existence can be assumed for a direct dependence of these changes upon activity failure by a few organules . Membrane permeability processes have resulted to be involved, which are the main metabolic paths in the defective ATP synthesis, and enzyme blockades responsible for peroxide accumulation.

Akush Ginekol (Mosk), 1989 Feb, (2), 33 - 5
{Clinico-laboratory diagnosis of chronic candidiasis of the external genital organs in women}; Khachaturian RE et al.; Major clinical characteristics of various forms of recurrent chronic external genital candidiasis in females and remission thereof are considered . Cytologic findings in vaginal smears are reported, as are the results of Candida albicans culture in vaginal discharge of patients with acute and subacute recurrences and those with remissions . Cytologic investigation is shown to be very valuable and capable of differentiating between various forms of the pathology when used in combination with the cultures . It was also valuable in the diagnosis of acute and suacute relapses of chronic candidiasis, the accuracy of diagnosis being 87.8% . High detectability rate of vegetating fungal forms may serve as an indicator of the activity of the pathologic process.

J Antibiot (Tokyo), 1989 Feb, 42(2), 174 - 8
L-671,329, a new antifungal agent . III . In vitro activity, toxicity and efficacy in comparison to aculeacin; Fromtling RA et al.; L-671,329 is a novel, echinocandin-like natural product that possesses potent anti-Candida activity, including activity against Candida parapsilosis . The in vitro MICs of L-671,329 were comparable to aculeacin against 18 yeasts and three filamentous fungi in an agar dilution assay . L-671,329 lysed mouse red blood cells (RBCs) at a concentration of 400 micrograms/ml, but not at 50 or 12.5 micrograms/ml . Aculeacin lysed RBCs at 400 and 50 micrograms/ml . L-671,329 significantly prolonged survival of mice infected with Candida albicans (ED50 3.38 mg/kg) following twice-daily intraperitoneal dosing for five consecutive days . The prolongation observed was greater than that seen with aculeacin therapy (ED50 6.44 mg/kg) . No acute or chronic toxicities of L-671,329 or aculeacin (as measured by mortality) were detected at a concentration of 100 mg/kg following intraperitoneal administration (TD50 greater than 100 mg/kg) . Both L-671,329 and aculeacin eradicated cells of C . albicans from the kidneys of infected mice . L-671,329 eradicated the yeast at therapeutic concentrations of 12.5 to 100 mg/kg . Aculeacin eradicated yeast cells at therapy concentrations of 25 to 100 mg/kg . L-671,329 has potential as an anti-Candida compound.

Oral Surg Oral Med Oral Pathol, 1989 Feb, 67(2), 177 - 80
Are postmortem studies of glossal candidal infection useful? An experimental study; Peters E et al.; Autopsy studies have suggested that candidal pseudohyphae may be found in dorsal glossal epithelium in 38% to 42% of cases . Candidal yeast forms, and occasionally free pseudohyphae, are found as oral commensals in about 44% of the population . This study examined the possible distorting influence in autopsy studies that could be caused by postmortem hyphal transformation of candidal yeast forms followed by saprophytic infestation . Candida albicans yeast forms were topically applied to the middorsal glossal mucosa of five healthy pigs, immediately after killing . Biopsy specimens from this mucosa were subsequently maintained, in vitro, for periods of 12 and 24 hours in humid conditions at different temperature regression rates chosen to approximate those of the oral cavity after death . Biopsy specimens subjected to a temperature regression of 35 degrees C (oral temperature) to 23 degrees C (room temperature) over 11 hours showed infestation of epithelium by pseudohyphae in all cases . Biopsy specimens subjected to a similar temperature regression over 5 hours showed infestation in two of five cases . Control biopsy specimens showed that there was no candidal infection at the time of killing . The results indicate that in vitro saprophytic candidal infestation is possible in the time intervals and the declining oral temperatures preceding autopsy . It suggests that postmortem saprophytic candidal infestation may distort results from autopsy studies that do not anticipate this problem.

J Med Microbiol, 1989 Feb, 28(2), 93 - 100
Effect of iron depletion on cell-wall antigens of Candida albicans; Paul TR et al.; Cell walls were isolated from stationary-phase cultures of Candida albicans grown at 25 degrees C or 37 degrees C, in iron-depleted and iron-sufficient conditions . Proteins solubilised from cell-wall fractions were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis . Approximately 40 protein bands were detected by Coomassie blue staining in all wall extracts, regardless of temperature or other growth condition . Sera from patients with oral or systemic candidosis, from whom the isolates were obtained, and pooled normal human serum were examined for the presence of IgG and IgM antibodies to cell-wall proteins by Western blotting . Patient sera recognised more antigens than pooled normal human serum . In particular, an antigen of 44 kda was detected by IgG antibodies in the sera of patients and two antigens of 41 and 14 kda were detected by their IgM antibodies when the sera were used as probes against walls from iron-depleted cells, but not from iron-sufficient cells, grown at 25 degrees C . Two antigens of 45 and 40 kda were detected by IgM antibodies in the sera of patients tested against walls from iron-depleted but not from iron-sufficient cells grown at 37 degrees C . IgG antibodies did not distinguish between these wall preparations from cells grown at 37 degrees C . These results suggest that the specific cell-wall proteins induced during growth in iron-depleted conditions, as well as other proteins, were immunogenic and were recognised by the patients' antibodies.

J Med Microbiol, 1989 Feb, 28(2), 85 - 91
Morphotype markers of virulence in human candidal infections; Hunter PR et al.; A study of the morphotypes of 446 strains of Candida albicans, isolated from a variety of clinical specimens, is reported . The method was based on a morphotyping scheme that has recently been described, but not all of the potential characters were used in this analysis . By this limited code, 50 different morphotypes were distinguished, the largest group comprising 23% of the population . The simplicity and good discrimination of the method make it a useful typing scheme for C . albicans . Discontinuous colonial fringes were associated with strains from oral sites and deep infections . Significantly, 67% of strains from fatal infections were of the discontinuous fringe type, compared to only 11% of strains from other infections . Further associations between morphotype and anatomical source included narrow-coarse fringes in genitourinary isolates.

Am J Hematol, 1989 Feb, 30(2), 86 - 90
Diffuse panbronchiolitis as a pulmonary complication in patients with adult T-cell leukemia; Ono K et al.; Forty-three cases of adult T-cell leukemia (ATL) admitted to our hospital between 1982 and 1987 were studied . Three of those were found to be complicated with diffuse panbronchiolitis (DPB) . The incidence of DPB is considered to be significantly higher in patients with ATL . The three DPB-complicated cases composed one case each of the smoldering, chronic, and acute type of ATL . In each type, DPB preceded overt ATL and Candida albicans was found in sputa following detection for bacteria . The DPB complication apparently worsened the prognosis of the ATL patients . We have discussed a possible relationship between ATL and DPB.

Infect Immun, 1989 Feb, 57(2), 527 - 32
Genetic differences between type I and type II Candida stellatoidea; Kwon-Chung KJ et al.; Genetic similarities and differences between type I and type II Candida stellatoidea were studied . The electrophoretic karyotype, mitochondrial DNA (mtDNA) restriction patterns, and midrepeat sequence of nuclear DNA in type I C . stellatoidea were clearly distinguishable from those of a reference culture of Candida albicans . The karyotype and the major bands of the midrepeat sequence of type II C . stellatoidea were indistinguishable from those of the reference C . albicans . The mtDNA restriction patterns of four type I isolates were homogeneous regardless of the endonucleases and probes used . The mtDNA restriction patterns of type II C . stellatoidea varied from strain to strain . Some of them were identical to that of C . albicans, while others were the same as that of type I C . stellatoidea . Immunofluorescence with C . albicans serotype A-specific monoclonal antibody indicated that the four isolates of type I C . stellatoidea were serotype B (non-A), whereas all three type II isolates studied were serotype A . Taken together, these results support the hypothesis that the isolates of C . stellatoidea type II studied are sucrose-negative mutants of serotype A C . albicans . Since C . stellatoidea type I differs from C . albicans in several major genetic characteristics, it cannot be viewed as a simple mutant derived from C . albicans . Hybrids produced by protoplast fusion of type I and type II cells were capable of assimilating sucrose, indicating that the sucrose-negative phenotypes of the parents are due to different mutations.

Infect Immun, 1989 Feb, 57(2), 458 - 67
Hypha formation in the white-opaque transition of Candida albicans; Anderson J et al.; Cells of Candida albicans strain WO-1 and related strains switch frequently and reversibly between a white-colony-forming unit (white phase) and a gray-colony-forming unit (opaque phase) . Cells in the budding white phase exhibit the usual smooth round phenotype observed in other C . albicans strains, but cells in the budding opaque phase exhibit a unique elongate shape with surface pimples or protrusions . In this study, it was demonstrated that opaque cells formed hyphae at low to negligible levels in suspension cultures but could be induced to form hyphae at high levels when anchored to the chamber wall of a perfusion chamber or to a monolayer of human skin epithelial cells . Variability in the proportion of hyphae formed between experiments appeared to be due to variability between individual opaque clones . The hyphae formed by opaque cells were morphologically identical to hyphae formed by white cells (i.e., they were devoid of pimples or protrusions and exhibited the same shape and septal locations) . They also did not stain with an opaque-specific antiserum which differentially stained opaque budding cells in a punctate fashion . However, when stimulated to form buds, opaque hyphae formed opaque-shaped daughter buds, demonstrating that although they are morphologically similar to hyphae formed by white cells, they are genetically opaque.

Infect Immun, 1989 Feb, 57(2), 413 - 9
Analysis of mannans of two relatively avirulent mutant strains of Candida albicans; Saxena A et al.; We previously reported the isolation of two cerulenin-resistant mutant strains of Candida albicans 4918 that differ in adherence properties and are less virulent than the parental strain . In addition, biochemical characterization demonstrated significant differences in both protein and polysaccharide composition of cell wall material between the mutant and wild-type strains . These observations prompted studies concerning the chemical structure of mannans in these strains . After extraction and subsequent purification by ion-exchange chromatography, mannan fractions were subjected to either mild acid hydrolysis, alkali hydrolysis, or acetylation followed by acetolysis . Acid- and alkali-modified mannans were studied by proton magnetic resonance spectroscopy, and released products were analyzed by high-performance liquid chromatography on an Aminex HPX-42A column . The results demonstrated quantitative and qualitative differences between mannooligosaccharides of the wild-type and mutant strains in the identity of released oligosaccharides as well as in linkage of the oligosaccharides to the protein backbone.

Nor Tannlaegeforen Tid, 1989 Feb, 99(4), 116 - 9
{Conventional treatment of oral candidiasis--new aspects}; Barkvoll P et al.; Polyene antibiotics such as nystatin and amphotericin B are among the most widely recommended drugs for use in the treatment of oral candidiasis . It is also generally accepted that chlorhexidine gluconate is an appropriate adjunct or an alternative to specific antimycotic drugs . The aim of the present paper was to discuss the conventional treatment against Candida albicans infections . It has previously been shown in an vitro study that combination of chlorhexidine and nystatin reduced the effect against Candida albicans . The most likely reason is that a low solubility chlorhexidine-nystatin salt is formed, thus rendering the combined drug complex ineffective as an antibiotic agent . Other pharmacologic interactions are also discussed . In the treatment of denture related candidiasis one should keep in mind that some tissue conditioners will inhibit the antifungal activity of amphotericin B . A more restrictive use of combinations of drugs against oral candidiasis is suggested.

Antimicrob Agents Chemother, 1989 Feb, 33(2), 147 - 51
Comparison of the efficacies of amphotericin B, fluconazole, and itraconazole against a systemic Candida albicans infection in normal and neutropenic mice; Van t Wout JW et al.; We compared the efficacies of the new triazole antifungal drugs fluconazole and itraconazole with that of amphotericin B in vitro and in an animal model of systemic candidiasis in normal and neutropenic mice . Antifungal treatment with fluconazole (2.5 to 20 mg/kg orally twice daily), itraconazole (10 to 40 mg/kg orally twice daily), or amphotericin B (0.1 to 4 mg/kg intraperitoneally once daily) was started 1 day after intravenous injection of 10(4) Candida albicans into normal mice or 10(3) C . albicans into neutropenic mice; the drugs were administered for 2 days . In normal mice the efficacy of treatment, which was assessed on the basis of the number of C . albicans cultured from the kidney, was greater for amphotericin B than for the triazoles . Fluconazole was more potent than itraconazole on the basis of equivalent doses, although itraconazole was more potent on the basis of the amount of free drug that was available . In neutropenic mice amphotericin B was less effective than it was in normal mice, whereas the triazoles were equally effective in normal and neutropenic mice . This was not expected, since in vitro data showed that amphotericin B was highly fungicidal, whereas both fluconazole and itraconazole had only a minimal effect on the growth of C . albicans in vitro.

Immunology, 1989 Feb, 66(2), 278 - 83
Suppression of monocyte functions by human cytomegalovirus; Buchmeier NA et al.; The role of the monocyte in human cytomegalovirus (HCMV)-induced immunosuppression was examined by assessing the ability of the virus to directly suppress various monocyte accessory cell functions . Both patient-derived and laboratory-adapted strains of HCMV were capable of impairing antigen-presenting functions of purified human monocytes . In seven of 12 virus-infected samples, there was a significant decrease (P less than 0.05) in the ability of HCMV-infected monocytes to present tetanus toxoid to autologous lymphocytes compared with mock-infected controls; similar results were obtained with Candida albicans and mumps . In contrast, the response to PHA was impaired in only one of eight HCMV-infected samples . The increased expression of MHC class II Ia antigens (HLA-DQ and HLA-DR) by monocytes after stimulation by interferon-gamma was impaired in approximately one-third of the 43 virus-infected samples tested . Interleukin-1 (IL-1) production after incubation with the stimulating antigens, however, was unaffected . Attempts to augment immuno-suppression by co-stimulation of monocytes with lipopolysaccharide (LPS), heat-killed Escherichia coli or Listeria monocytogenes were not successful; however, dramatically increased levels of immunosuppression was obtained with HCMV preparations containing mycoplasma . Thus, although HCMV is capable of directly perturbing monocyte accessory cell functions, the variability and partial suppression observed suggests that infection of monocytes by HCMV alone is not sufficient to produce the levels of immune hyporesponsiveness observed in HCMV-infected patients.

Bratisl Lek Listy, 1989 Feb, 90(2), 125 - 8
{Evaluation of the antimicrobial effect and toxicity of glutaraldehyde}; Volna F et al.; The antimicrobial efficacy and toxicity of a solution containing 20 g.l-1 glutaraldehyde was evaluated . All the tested germs of gram-negative microorganisms and of the strain Staphylococcus aureus were killed within 5 minutes, those of mycobacteria within 120 minutes, and bacterial spores in the course of 240 minutes . The fungicidal effect of the solution upon the strain Candida albicans became manifest after 10 minute exposure and upon the tested genera of dermatophytes after 30 minute exposure . The bacteriophage phi X 174 was inactivated within 60 minutes . In the view of the obtained values of its antimicrobial efficacy and toxicity, glutaraldehyde is recommended as a chemosterilizing substance.

Infect Immun, 1989 Feb, 57(2), 616 - 22
C3bi-binding protein on Candida albicans: temperature-dependent expression and relationship to human complement receptor type 3; Eigentler A et al.; We investigated in detail the previously described capacity of pseudohyphae of Candida albicans to bind C3-coated particles . We show that the expression of the C3bi receptor of C . albicans was dependent upon the growth temperature of the fungi . C . albicans grown at 30 degrees C bound strongly to EAC1423bi, whereas those cells grown at 38.5 degrees C were completely devoid of this capacity . The molecule responsible for the attachment of EAC1423bi was heat labile and trypsin sensitive . Several, but not all, monoclonal antibodies to the alpha-chain of human complement receptor type 3 (CR3) stained C . albicans, and this reactivity was expressed in parallel with the capacity of C . albicans to bind EAC1423bi, i.e., both were dependent on the growth temperature of the fungi and were trypsin sensitive . In contrast to CR3, the binding of EAC1423bi to C . albicans did not require the presence of divalent cations . Rabbit immunoglobulin G antibodies directed against C . albicans inhibited the binding of EAC1423bi to C . albicans but not to human CR3 . These inhibiting IgG antibodies recognized antigens expressed on the surface of pseudohyphae but not those of yeast cells . OKM-1, a monoclonal antibody to human CR3 inhibited the attachment of EAC1423bi to CR3 and also to C . albicans . OKM-1 precipitated a 130-kilodalton band from solubilized 125I-labeled C . albicans . We conclude that the complement receptors on C . albicans and human CR3 were antigenically related but not identical and that they differed in their functional characteristics.

J Gen Microbiol, 1989 Feb, 135 ( Pt 2), 309 - 14
Purification and some properties of Candida albicans exo-1,3-beta-glucanase; Molina M et al.; An exo-1,3-beta-glucanase was purified from blastoconidia of Candida albicans 1001 . The purified enzyme appeared as a single protein band by PAGE, and split into two subunits (Mr approximately 63,000 and 44,000) when analysed by SDS-PAGE . The pI of the enzyme was 4 and a Km of 1.7 mg ml-1 was estimated for laminarin as substrate . Despite its very reduced activity on the synthetic substrate p-nitrophenyl beta-D-glucoside, C . albicans exo-1,3-beta-glucanase hydrolysed 1,3-beta-glucan by an exo-splitting mechanism and was inhibited by glucono-delta-lactone and by Hg2+ and Ag+ cations . The active exo-glucanase was mainly located in the periplasm, but it was also present inside the cytoplasmic membrane in small amounts and was secreted into the culture medium . The electrophoretic mobility of the enzyme from all three locations was the same.

Mycopathologia, 1989 Feb, 105(2), 87 - 92
Mannan and D-arabinitol concentrations in serum from a patient with Candida albicans endocarditis; Fujita S et al.; In an attempt to clarify the comparative values of serological and microbiological examinations for the early diagnosis of systemic candidiasis, antibodies against Candida albicans, serum mannan, and the D-arabinitol creatinine ratio were investigated in a patient with aortic valve endocarditis associated with carcinoma of the bile duct . Candida precipitins and the antibody titer against Candida cell wall mannan were examined by an immunodiffusion technique and hemagglutination test, respectively . Serum mannan was tested by enzyme-linked immunosorbent assay (ELISA) using the biotin-streptavidin procedure . The upper limit of negativity of the assay was determined by adding 0.06 to the absorbance of pooled serum from healthy laboratory workers . This value was about 0.8 ng/ml with ELISA . The D-arabinitol concentration in serum was examined by an enzymatic fluorometric method . Rising antibody titers against C . albicans, mannan antigenemia, and an elevated D-arabinitol creatinine ratio were first observed between the 11th and 12th hospital days . Blood cultures obtained on 8th, 9th, and 11th hospital days grew C . albicans after 3 to 4 days of incubation . Of 11 serum samples, 5 were positive for mannan, whereas D-arabinitol creatinine ratio was positive in 7 of 9 samples . Blood cultures was the earliest evidence of Candida infections in our cases . However, because of saprophytic nature of Candida species, tests for antibodies, antigenemia, and the D-arabinitol creatinine ratio in combination with blood cultures are necessary to confirm systemic candidiasis at an early stage of infection.

Antimicrob Agents Chemother, 1989 Feb, 33(2), 152 - 5
Effects of free and liposomal amphotericin B and gramicidin S alone and in combination on potassium leakage from human erythrocytes and Candida albicans; Midez JA et al.; We studied the toxic effects of amphotericin B and gramicidin S, alone and in combination, using free and liposome-encapsulated drugs . In vitro toxic effects of the drugs on human erythrocytes and Candida albicans were determined by measuring leakage of intracellular potassium ions (K+) . Liposomal formulations of both drugs greatly reduced K+ leakage from human erythrocytes, whereas liposomal gramicidin S, but not liposomal amphotericin B, prevented K+ leakage from C . albicans . In both free and liposomal forms, the combinations of drugs produced decreased toxicity to erythrocytes compared with the drugs alone . This protective effect was more apparent with liposomal combinations than with free drug combinations . A significant increase in fungal cell toxicity was observed, however, when free and liposomal drug combinations were tested against C . albicans . The results suggest that optimal concentrations of liposomal drug combinations (amphotericin B and gramicidin S) may provide increased toxicity against fungal cells and simultaneously protect mammalian cells.

Tidsskr Nor Laegeforen, 1989 Jan 30, 109(3), 357 - 60
{Candida albicans--is it causing a new national disease?}; Sandven P; A hypothesis concerning a chronic candida hypersensitivity syndrome caused by the presence of Candida albicans in the gut was put forward in the USA a decade ago . Lately this theory has gained much publicity in Norway through articles in the press and programs on the national radio and television . The purpose of this article is to give a presentation and critical evaluation of this syndrome . It is concluded that the theory of a chronic Candida hypersensitivity syndrome is speculative and devoid of experimental support.

J Immunol Methods, 1989 Jan 17, 116(2), 213 - 9
Development of a microsphere-based fluorescent immunoassay and its comparison to an enzyme immunoassay for the detection of antibodies to three antigen preparations from Candida albicans; McHugh TM et al.; A sensitive assay for the simultaneous detection of multiple serum antibodies by flow cytometry was developed . Polystyrene microspheres of 5, 7 and 9.3 micron in diameter were used as solid supports for the attachment of three different antigen preparations from Candida albicans . These antigens were a whole cell extract; a cytoplasmic protein extract and a cell wall polysaccharide . Microsphere-associated fluorescence was quantitated by flow cytometry, with the different sized microspheres analyzed separately using electronic volume gating . This procedure allowed for different antigen-coated microspheres with discrete sizes to be analyzed independently for immunofluorescence . The assay detected antibody levels in human serum at dilutions up to 10(-6) and provided complete discrimination, using all three antigen preparations, between antibody levels seen in healthy subjects and those seen in patients suspected of having a systemic Candida infection . A standard enzyme immunoassay (EIA) failed to provide complete discrimination between healthy subjects and patient samples: at least 17% of patient values fell within the healthy subject range using all three antigen preparations . The microsphere assay which allowed for the simultaneous detection of multiple antibodies, has increased dynamic range over EIA and provides for better discrimination of patients from healthy subjects in comparison to EIA . Precise quantitation of antibodies is possible and the rapid analysis of thousands of microspheres markedly enhances the statistical accuracy of the assay . We suggest this assay is likely to have many other important applications in immunologic testing.

FEMS Microbiol Lett, 1989 Jan 15, 48(2), 167 - 71
Isolation of hydrophobic and hydrophilic variants of Candida albicans; Hazen BW et al.; We have previously demonstrated that most isolates of C . albicans are hydrophobic when grown at room temperature (RT, ca . 22-24 degrees C) and hydrophilic when grown at 37 degrees C . Variants of our standard strain LGH1095 were isolated that are hydrophobic at 37 degrees C and hydrophilic at RT . After repeated phase partitioning with cyclohexane-water cell populations that were 6-16% hydrophobic at RT and 66-80% hydrophobic at 37 degrees C were obtained . Subsequent limiting dilution experiments provided clones which were more hydrophobic at RT or hydrophilic at 37 degrees C . These were then recloned until the resultant populations were consistently under 5% cell surface hydrophobicity (CSH) at RT or over 95% at 37 degrees C . Treatment with several detergents as well as sugars did not decrease the CSH of these cells . Lipase and several proteases also had no effect . When treated with trypsin at a concentration twice that used to lower CSH of normal cells to less than 5%, the hydrophobic variant only decreased in CSH by 50% . Both variants were capable of germinating, although at different levels depending on prior growth temperature . Sensitivity to the germination inhibitor morphogenic autoregulatory substance (MARS) was similar to that of the parent strain.

J Biol Chem, 1989 Jan 15, 264(2), 1100 - 7
Characterization of Candida albicans dihydrofolate reductase; Baccanari DP et al.; Dihydrofolate reductase from Candida albicans was purified 31,000-fold and characterized . In addition, the C . albicans dihydrofolate reductase gene was cloned into a plasmid vector and expressed in Escherichia coli, and the enzyme was purified from this source . Both preparations showed a single protein-staining band with a molecular weight of about 25,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis . The enzymes were stable and had an isoelectric point of pH 7.1 on gel isoelectric focusing . Kinetic characterization showed that the enzymes from each source had similar turnover numbers (about 11,000 min-1) and Km values for NADPH and dihydrofolate of 3-4 microM . Like other eukaryotic dihydrofolate reductases, the C . albicans enzyme exhibited weak binding affinity for the antibacterial agent trimethoprim (Ki = 4 microM), but further characterization showed that the inhibitor binding profile of the yeast and mammalian enzymes differed . Methotrexate was a tight binding inhibitor of human but not C . albicans dihydrofolate reductase; the latter had a relatively high methotrexate Ki of 150 pM . The yeast and vertebrate enzymes also differed in their interactions with KCl and urea . These two agents activate vertebrate dihydrofolate reductases but inhibited the C . albicans enzyme . The sequence of the first 36 amino-terminal amino acids of the yeast enzyme was also determined . This portion of the C . albicans enzyme was more similar to human than to E . coli dihydrofolate reductases (50% and 30% identity, respectively) . Some key amino acid residues in the C . albicans sequence, such as E-30 (human enzyme numbering), were "vertebrate-like" whereas others, such as I-31, were not . These results indicate that there are physical and kinetic differences between the eukaryotic mammalian and yeast enzymes.

Rev Fr Gynecol Obstet, 1989 Jan, 84(1), 15 - 7
{Advantages of single-dose treatment of vaginal Candida albicans infection}; Blum M et al.; One-hundred forty women (60 pregnant and 80 non-pregnant women) with a history of Candida albicans infection were examined one month before treatment and were reexamined one month after treatment . Administration of a single agent consisting of 2,300 mg tablets of GynoTragoven (isoconazole nitrate, Schering, AG) resulted in immediate clinical improvement . One month after treatment, the success rate was 85-100 p . cent for non-pregnant women, and 83-100 p . cent for pregnant women . No side-effects were observed following therapy . According to studies published, a high percentage of infections develop during pregnancy, especially during the second (35 p . cent) and third (31.5 p . cent) trimesters . Because of the high rate of infections during pregnancy, preventive therapy should be considered during the final weeks of pregnancy, to prevent intrauterine infection during parturition.

Infect Immun, 1989 Jan, 57(1), 186 - 90
Candidacidal activities of proteins partially purified from rat epidermis; Kashima M et al.; Proteins with approximate molecular weights of greater than 300,000 (EP greater than 300K) and 49,000 (EP 49K) were partially purified from terminally differentiated cells of 2-day-old rat epidermis . They were extracted in 0.34 M sucrose containing 0.01 M citric acid and purified by Sephacryl S-300 chromatography followed by reverse-phase column chromatography . The major constituents of EP greater than 300K and EP 49K were focused around pH 10 to 11 by sucrose gradient isoelectric focusing . Both proteins were effective at inhibiting colony formation of Candida albicans and C . tropicalis, but neither inhibited the growth of C . parapsilosis . The effect was maximum below pH 5.0 and reduced considerably above pH 5.0 . The activity of EP greater than 300K on C . albicans TIMM 1623 (group A) was much stronger than that of EP 49K, whereas both proteins similarly inhibited C . albicans TIMM 1604 (group B) . Their effects against C . albicans TIMM 1623 were dose dependent and were activated after a longer preincubation time, and NaCl concentration influenced their potency . At a low salt concentration and a 60-min preincubation at pH 4.5, the 50% effective dose for EP greater than 300K was calculated to be 1.7 x 10(-9) M, whereas that for EP 49K was 1.8 x 10(-7) M.

J Int Med Res, 1989 Jan-Feb, 17(1), 82 - 6
The use of 2.5% natamycin, as orally administered drops, in the treatment of fungal infections of the oral cavity in children with chronic blood diseases; Rokicka-Milewska R et al.; A total of 34 children with oral candidiasis were treated with 2.5% natamycin in the form of orally administered drops; 6-20 drops applied to oral lesions four times daily for up to 8 weeks . A total cure was achieved in 28 (82.3%) cases . No side-effects were observed . This preparation was an effective treatment for Candida albicans infections in children with blood diseases, and was well tolerated.

Nippon Ganka Gakkai Zasshi, 1989 Jan, 93(1), 109 - 17
{Experimental Candida albicans chorioretinitis}; Hirano Y; The long term (12 months) clinical and histopathological features of experimental chorioretinitis induced by intravenous injection of Candida albicans (5-10 x 10(6) spores) in pigmented rabbits were reported . Nine of 26 animals developed bilateral and 11 of 26 animals unilateral chorioretinal lesions . The lesions were round, yellow-white spots initially growing with a fluffy border, and breaking into the vitreous body . Finally, the lesions became chorioretinal scars with bridging strands in the vitreous body . Histologically, the initial lesions were subretinal microabscesses of pseudoeosinophils with PAS-positive spores, then macrophages invaded and typical granuloma with epithelioid and multinucleated giant cells developed . One year after the inoculation, focal chorioretinal scars with vitreous strands were found.

Bull Soc Pathol Exot Filiales, 1989, 82(2), 201 - 7
{Fungal otitis in Libreville . Study of 83 cases}; Kombila M et al.; 83 cases of mycotic otitis of external ear are reported during a period of 27 months from three departments of otorhinolaryngology in Libreville (Gabon, Central Africa) Prevalence is estimated at about 25% among all infectious otitis . The main functional signs are pruritus, otorrhea, pain and hypoacousia . The physical examination shows masse of white, grey, black or creamy caseous debris, invading the external auditory meatus (EAM) which is sometimes inflammatory . Fungal species responsible of otitis are Aspergillus (54%), yeasts (45%) mainly Candida, infrequently Fusarium (1%) . A niger (26%), A . flavus (17%), Candida parapilosis (18%), Candida albicans (9%) are predominant species isolated (70%) among all the 21 species of identified fungi from otomycosis in Gabon . Therapy, done by thorough washing of the ear followed by insertion into the EAM of a wick soaked in Econazole or Amphotericin B, is quickly effective.

Farmaco, 1989 Jan, 44(1), 65 - 76
{Substances with antibacterial and antifungal activity . VII . Synthesis and microbiologic activity of new derivatives of 1,5-diarylpyrrole}; Porretta GC et al.; The synthesis and antifungal activities of new 1,5-diarylpyrrole derivatives are reported . Antimicrobial data in comparison with pyrrolnitrin show that N-methylpiperazinylamides exhibit very poor activity against Candida albicans and Candida sp . while acid and ester derivatives are inactive . Vice-versa many acid or amide derivatives show interesting antibacterial activity . The results obtained are discussed on the basis of structure-activity relationships.

Arch Gynecol Obstet, 1989, 244(3), 175 - 7
Intrauterine fetal death apparently due to Candida chorioamnionitis; Bider D et al.; There is an increasing awareness of the association between Candida albicans chorioamnionitis and preterm labor . We present a case of intrauterine fetal death caused by Candida chorioamnionitis at the 21 weeks gestation in a patient with an intrauterine device (IUD).

J Pediatr Gastroenterol Nutr, 1989 Jan, 8(1), 125 - 8
Blastocystis hominis gastroenteritis in a hemophiliac with acquired immune deficiency syndrome; Narkewicz MR et al.; Blastocystis hominis is an enteric protozoan that has occasionally been associated with gastrointestinal illness in man but is not considered an opportunistic pathogen . We describe a 16-year-old hemophiliac with acquired immune deficiency-related complex in whom upper gastrointestinal symptoms in conjunction with high densities of B . hominis in duodenal secretions and stool developed . Furazolidone treatment was associated with eradication of the organism and improvement in clinical symptoms . One month later, the patient had invasive Candida albicans esophagitis and died 2 weeks later of complications of acute pancreatitis . In immunocompetent individuals surveyed in Colorado the frequency of identification of B . hominis in stool concentrates was not different between asymptomatic and symptomatic persons . We suggest that B . hominis may be an opportunistic pathogen in immunocompromised patients and should be sought in duodenal secretions and feces when gastrointestinal symptoms are present.

Pancreas, 1989, 4(1), 120 - 2
Pancreatic abscess secondary to Candida albicans; Howard JM et al.; A case report is presented of a patient with acute postoperative pancreatitis who developed a pancreatic abscess secondary to Candida albicans . Recovery followed operative drainage and amphotericin B therapy . Because this is the only such patient in the author's career experience, and because only one other report currently addresses the problem, this report is offered.

Clin Exp Rheumatol, 1989 Jan-Feb, 7(1), 43 - 6
Cineradiography identifies esophageal candidiasis in progressive systemic sclerosis; Geirsson AJ et al.; Cineradiography of the esophagus showed signs of esophageal candidiasis in 11 out of 71 patients with progressive systemic sclerosis (PSS) - both in diffuse scleroderma and the CREST syndrome . Culture of esophageal brushings confirmed the presence of Candida albicans in eight of these 11 patients . Antimycotic treatment decreased the cineradiographic signs of candidiasis and the degree of dysphagia . Since impaired esophageal motility and treatment with immunosuppressive drugs may predispose to candida esophagitis, and since dysphagia will decrease after antimycotic treatment esophageal mycosis should always be sought in patients with PSS.

Pediatr Neurosci, 1989, 15(3), 125 - 30
Candida albicans shunt infection; Shapiro S et al.; Seven cases of successfully treated Candida albicans cerebrospinal fluid shunt infections are reported . Treatment consisted of shunt removal and intravenous Amphotericin B in all cases and intraventricular Amphotericin B in 4 cases . Serious underlying medical illness, recent antibiotic therapy, indwelling intravascular and/or Foley catheters, coincident candidiasis and low birth weight prematurity are major risk factors for candida shunt infection . Candida shunt infection appears to occur by either contamination at the time of shunt placement or by hematogenous dissemination.

Biotherapy, 1989, 1(4), 313 - 7
Options for the treatment of serious infections with interleukin-1; van der Meer JW; In this paper, the effects of recombinant human interleukin-1 (IL-1) on non-specific resistance to infection are reviewed . In experiments in neutropenic mice, a single injection of a low dose of IL-1 (8-800 ng) appears to protect against death from lethal Pseudomonas aeruginosa and Candida albicans infections . In non-neutropenic mice protection can also be obtained with such dosages of IL-1 in infection caused by Klebsiella pneumoniae or Listeria monocytogenes . Low dosages of IL-1 are also able to prevent lethal cerebral malaria in mice . No effect has been found in murine cytomegalovirus infection . With the exception of C . albicans infection and malaria, protection is only obtained if IL-1 is given before the infection . The mechanism of protection has not been elucidated; in the Pseudomonas and Klebsiella infection, it could be demonstrated that survival was not due to a direct antibacterial effect of IL-1, not due to the action of granulocytes or increased hematopoietic recovery and not due to activation of macrophages and increased bactericidal mechanisms . In the experimental Listeria infection however, animals treated with IL-1 had lower bacterial counts in their organs . Since the cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF) are much less potent than IL-1 in these protection experiments, it is very unlikely that they are endogenous mediators of the protection induced by IL-1 . The effect is not mediated via the cyclooxygenase pathway, since premedication with ibuprofen does not influence the protective effect of IL-1 . Taking these data together, it is felt that IL-1 holds promise as a therapeutic agent in humans.

Adv Microb Physiol, 1989, 30, 53 - 88
Current trends in Candida albicans research; Datta A et al.; Candida albicans is an opportunistic pathogen of human beings and other mammals . Two other features, besides its pathogenicity, have made it a popular organism of study . It exists in different cellular forms and can change from one form to another, depending on growth conditions . Thus, it is being used as a model system to study cellular differentiation . It can also heritably and reversibly switch its cellular and colony morphologies . The yeast is diploid and lacks a sexual cycle . Thus, it has not been possible to apply the powerful methods of genetic analysis to understand morphogenesis or pathogenesis . Few clinical isolates are haploid, but they do not form hyphae and are not yet well characterized . Recombinant DNA techniques are increasingly being applied to C . albicans to solve many of the unanswered questions of morphogenesis and pathogenesis . Genetic transformation and gene-disruption techniques were recently developed for the yeast . Thus it is possible to study the role of any cloned gene through directed mutagenesis . However, the difficulty is to clone the putative genes involved in morphogenesis or pathogenesis . Candida albicans exists in four different cellular forms, namely blastospores, pseudohyphae, hyphae and chlamydospores . Blastospore-to-hypha conversion is well studied . A variety of conditions can induce this transition . It is not clear how cells sense such varied conditions and respond appropriately . In other systems where differentiation is well understood, regulatory genes which control differentiation have been uncovered . These genes cause differential expression of other genes, and ultimately differentiated phenotypes . Thus, it is likely that differential gene expression is involved in the bud-to-hypha transition in C . albicans . Certain proteins are expressed exclusively on the cell surface of hyphae . It should be possible to clone genes coding for these proteins . A study of the expression of these genes might allow us to identify the regulatory gene which determines differentiation . Another approach to understanding morphogenesis is to study how the difference in the shape of buds and hyphae is generated . This difference appears to be due to the differential activity of apical and general growth zones, which determine growth of the cell wall . Activity of these growth zones is apparently determined by actin localization . It remains a possibility that conditions which induce hyphae formation may directly affect actin localization or cell-wall growth zones and cause differences in cell shape . Candida albicans can also heritably switch its cellular phenotype . This has come to light from a study of colony-morphology switching . Some strains can switch their colony morphology, both heritably and reversibly.(ABSTRACT TRUNCATED AT 400 WORDS)

Braz J Med Biol Res, 1989, 22(10), 1251 - 4
Participation of mannose receptors on the surface of stimulated macrophages in the phagocytosis of glutaraldehyde-fixed Candida albicans, in vitro; Felipe I et al.; We have evaluated the participation of mannose receptors on the surface of stimulated macrophages in the phagocytosis of Candida albicans in vitro . A dose-dependent 8.6 to 88.3% reduction of phagocytosis was observed in the presence of 0.5 to 5.0 mg/ml of the mannose-rich glycoprotein invertase (either native or denatured) in the incubation medium . Macrophages plated onto substrates coated with poly-L-lysine-mannan also showed a 99% reduction of phagocytic activity toward Candida albicans, but phagocytosis of IgG-coated erythrocytes was not inhibited under the same conditions . These results indicate that mannose receptors are involved in one of the initial steps of phagocytosis of Candida albicans by macrophages.

Mycoses, 1989, 32 Suppl 2, 6 - 8
International Workshop on Oral and Gastrointestinal Candidosis: From Pathology to Therapy . Introduction; Braun-Falco O; Oral candidosis is the manifestation of candidosis earliest described . In fact pertinent cases are already to be found in the corpus hippocraticum . Exactly 150 years ago a fungus was found in lesions of orogastrointestinal candidosis by the German surgeon Langenbeck . For a long time, there was much dispute on the proper term for the most important causative organism of thrush and correspondingly for the proper name of the diseases caused . Today, Candida albicans is accepted by virtually everybody and the discussion on the name of the disease only focuses on the terms candidiasis and candidosis of which the latter seems preferable . Facing the scientific progress in the field of Candida and candidosis research and the permanent change of both the causative organism and the corresponding disease in the age of the HIV-infection (AIDS), it seems rewarding to review epidemiology, microbiology, nosology and treatment of oral and gastrointestinal candidosis.

Mycoses, 1989, 32 Suppl 2, 47 - 51
Change of causative organisms under antifungal treatment in immunosuppressed patients with HIV-infections; Just G et al.; Oral and esophageal candidosis are very common in HIV-infected patients . Due to the lack of efficacy of topical antimycotics in advanced stages of HIV-infection oral azoles are mainly used for treatment . Azoles most often used are ketoconazole and fluconazole . While Candida albicans clearly is the most frequently encountered yeast before and after treatment other species can be found somewhat less frequently after treatment . This especially applies to Candida glabrata . Candida spp . other than C . albicans obviously may cause manifest oral candidosis . This shift of microbes deserves the more interest as they are less susceptible to azole drugs.

Mycoses, 1989, 32 Suppl 2, 23 - 9
Clinical spectrum of oral candidosis and its role in HIV-infected patients; Korting HC; Oral candidosis is a very frequent diseased state occurring mainly together with severe underlying disease . Clinical manifestation is variable . One can distinguish between oral thrush, denture stomatitis, angular cheilitis, leukoplakia and midline glossitis . Nowadays oral candidosis is also important in connection with HIV-infection . Here the clinical spectrum does not seem to be totally different . Apart from oral thrush (or pseudomembraneous type) a chronic atrophic type, a chronic hyperplastic type, papillary hyperplasia and angular cheilitis are distinguished . Oral candidosis is the most frequent opportunistic infection in HIV-infected patients . Frequency of overt disease is linked to the T4/T8 ratio . In patients with AIDS-related complex oral candidosis seems to be indicative of rapid progression . Candida albicans is the prevailing microorganism . There is, however, a change of biotypes during the course of HIV-infection . There seems to be a selection of certain phenotypes as can be judged from the increasing resistance to 5-fluorocytosine.

Mycoses, 1989, 32 Suppl 2, 18 - 22
Candidosis: diagnostic tools in the laboratory; Ruchel R; The diagnosis of deep-seated candidosis still poses severe problems to the physician . While laboratory tests for a long time have been mainly based on the detection of antibodies to Candida and in particular Candida albicans the detection of Candida antigen in the blood gains more and more interest . When it comes to the evaluation of the various laboratory tests the correlation with autopsy data is most rewarding . The more specimens are analysed for the presence of hints at deep-seated candidosis in a given hospital setting the least frequent death due to deep-seated candidosis occurs.

Mycoses, 1989, 32 Suppl 2, 12 - 7
Host-parasite relationships in candidosis; Calderone RA; Candida albicans has several properties which allow it to colonize and invade host tissues, often resisting eradication . Two of these properties, adherence and acid proteinase production, seem to be genuine factors . Phenotypic switching and molecular mimicry may also provide the organism with an arsenal of mechanisms to evade host defenses.

Ann Pharm Fr, 1989, 47(3), 157 - 61
{Antifungal effects in vitro of jasmon and some similar compounds . Structure-activity relationship}; Millet-Clerc J et al.; The antimycotic activity in vitro of jasmon and 6 closely related substances has been tested against four different dermatophytes, Candida albicans, Pityrosporum ovale and Aspergillus fumigatus . Jasmon had the highest activity . Among the other substances tested only thiazolidines with a carbonyl function developed antifungal properties against dermatophytes . 2,4 thiazolidinedione at 450 ppm inhibits the growth of Trichophyton rubrum.

Medicina (B Aires), 1989, 49(1), 43 - 7
{Pharmacokinetic interaction of ketoconazole, isoniazid and rifampicin}; Pilheu JA et al.; Eight male tuberculous patients, between 20 and 60 years of age, were given Isoniazid 5 mg/kg and Ketoconazole 200 mg, first one at a time and then associated . Plasma concentrations were measured 0, 2 and 5 hs after taking the drugs . Isoniazid was measured by spectrophotometry and Ketoconazole by the microbiologic method with Candida albicans as test microorganism . When both drugs were given simultaneously Ketoconazole plasma concentration decreased 75% at 2 hs (p less than 0.025) and 85% at 5 hs (p less than 0.05), whereas that of Isoniazid remained unchanged (Table 1) . Mean half-life of Isoniazid was 3.9 +/- 1.4 hs in 7 slow acetylators and 1.1 hs in one fast acetylator when given one at a time and 4.4 +/- 1.5 hs when given simultaneously . A similar study was conducted on 11 tuberculous patients who were given Rifampicin 10 mg/kg and Ketoconazole 200 mg, one at a time and concurrently . Rifampicin was measured by high pressure liquid chromatography . When Rifampicin and Ketoconazole were given concurrently plasma concentration of both drugs was reduced: Ketoconazole decreased 85% at 2 hs (p less than 0.025) and 98% at 5 hs (p less than 0.025) whereas Rifampicin decreased 45% at 2 hs (p less than 0.005) and 40% at 5 hs (p less than 0.005) (Table 2) . Mean half-life of Rifampicin was 3.5 +/- 0.8 and 4.2 +/- 1.1 hs, respectively, when it was given alone and concurrently . Studies on chemical interactions between Isoniazid and Ketoconazole and between Rifampicin and Ketoconazole yielded negative results.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytobios, 1989, 60(240), 11 - 20
Ultrastructure and possible processes involved in the invasion of host epithelial cells by Candida albicans in vaginal candidosis; Rajasingham KC et al.; Ultrastructural studies of Candida albicans in its invasive form obtained from lesions of patients with vaginal candidosis confirm that growth is intracellular . The invading hyphae show well defined organelles including a denticulate double-layered plasma membrane, nuclei, cristate mitochondria, endoplasmic reticulum and storage granules, especially when osmium tetroxide was used as the sole fixative for electron microscopy . The invasion of host epithelial cells is probably brought about by a combination of enzymatic, physical and mechanical processes.

J Med Vet Mycol, 1989, 27(6), 345 - 52
Interaction of Candida albicans with murine gastrointestinal mucosa: effect of irradiation on adherence in vitro; Sandovsky-Losica H et al.; The aim of this study was to investigate the adherence in vitro of Candida albicans to various parts of the gastrointestinal (GI) mucosa from irradiated and non-irradiated mice and to attempt to inhibit this adhesion with a chitin derivative . Adhesion was assayed using 3H-leucine labelled yeast, to which GI tissue-disks removed from irradiated (400R Cobalt) and non-irradiated animals were exposed at various time intervals post-irradiation . In non-irradiated mice differences in adherence of C . albicans to various parts of the GI tract were observed, the highest adherence being to duodenal tissues . In irradiated mice, an increase in adherence to all parts of the GI mucosa was observed . Based on findings from previous studies that a chitin derivative (CSE) inhibits adhesion of C . albicans to various tissues in vitro and in vivo, we tested the effect of CSE on the adhesion of C . albicans to GI tissues . The results show that CSE inhibited the adhesion of C . albicans to GI tissues from both irradiated and non-irradiated mice by 75-85% . The relevance of the findings to the pathogenesis of candidiasis is discussed.

Med Cutan Ibero Lat Am, 1989, 17(5), 326 - 31
{Oral hairy leukoplakia . A study of 5 cases}; Pujol C et al.; Oral hairy leukoplakia (HL) is a newly described lesion (1984) in human immunodeficiency virus infected patients . Patients with HL show a high probability of developing an acquired immunodeficiency syndrome (AIDS) . The results of histopathological, microbiological, immunological and ultrastructural studies in five patients with HL and AIDS are reported . The histopathological exam revealed in all cases acanthosis, parakeratosis, koilocytosis and keratin projections on the surface . Dermis was normal . Herpes type virus were seen in four cases and in one of them papilloma virus was also present in electron microscopic examination . There was immunocytochemical evidence of papilloma virus in one lesion . Candida albicans was found in 5 lesions by culture but only in two ones by periodic acid Schiff stain . Virus cultures for herpes virus were negative . Immunocytochemical search of Langerhans cells (S-100, HLA-DR, OKT4, OKT6) showed nearly absence of these cells in HL lesions . These results favour the viral etiology hypothesis of hairy leukoplakia.

J Basic Microbiol, 1989, 29(8), 527 - 35
Unidirectional internuclear transfer of linked genes in heterokaryons of Candida albicans; Sarachek A et al.; Nutritionally balanced heterokaryons of the naturally diploid, asexual yeast, Candida albicans are produced by fusing protoplasts of complementing auxotrophic strains . Spontaneous unidirectional internuclear transfers of an intact gene linkage group in established heterokaryons is demonstrated . Evidence is presented that a transfer event (i) typically involves a single chromosome which is added to the resident homologues of a recipient nucleus, (ii) can occur equally well in either direction between complementing nuclei and (iii) may encourage gene conversion at transferred loci in the recipient nucleus . The bearing of these findings on application of protoplast fusion to parasexual genetic analysis of C . albicans is discussed.

Curr Med Res Opin, 1989, 11(9), 567 - 75
A double-blind clinical trial of fenticonazole (2%) spray versus naftifine (1%) spray in patients with cutaneous mycoses; Leiste D et al.; A multi-centre, double-blind trial was carried out in 100 patients with cutaneous mycotic infections, confirmed by direct microscopy and/or culture, to compare the efficacy and tolerability of spray formulations of 2% fenticonazole and 1% naftifine . On entry, patients were allocated at random to receive once daily topical applications of one or other drug over a period of 2 to 4 weeks, treatment being stopped when patients had recovered or substantially improved . Clinical and mycological assessments were made before (baseline), at weekly intervals during treatment and, if possible, 2 to 3 weeks after the end of treatment (drug-free period) . Treatment was continued for 19.25 days with fenticonazole and 19.62 days with naftifine . All patients had positive mycological findings on entry . The most frequently isolated pathogens were dermatophytes, mainly Trichophyton rubrum; however, Candida albicans was present in 33.3% of patients in the fenticonazole group and in 20.8% of those treated with naftifine . At the end of treatment, only 3 (6.3%) and 5 (10.4%) patients, respectively, of the 48 patients assessed in each group still had positive mycological findings . Assessments of symptoms indicated comparable, significant improvement in both groups, and at the end of treatment the overall opinion of doctors and patients was that about 90% of patients were cured or greatly improved . The end of the drug-free period evaluation showed that, of the patients assessed as cured or greatly improved at the end of treatment, only 1 (3.2%) patient who had received fenticonazole and 2 (6.3%) who had received naftifine were confirmed mycologically as having relapsed.(ABSTRACT TRUNCATED AT 250 WORDS)

Microbios, 1989, 60(243), 79 - 86
Mitochondrial behaviour during the yeast-hypha transition of Candida albicans; Aoki S et al.; Yeast cells of Candida albicans were brought to germ tube formation and hyphal growth in liquid synthetic medium . The behaviour of mitochondria and mitochondrial nucleoids (mt-nucleoids) during morphological conversion was examined by fluorescence staining with 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide (DASPMI) and 4',6-diamidino-2-phenylindole (DAPI) . Parent yeast cells possessed one or very few branched giant mitochondria which were stained intensely with DASPMI . When a germ tube emerged from the parent cell, one end of a giant mitochondrion extended into the germ tube and developed into the elongated form . In mycelia, apical hyphal cells contained giant mitochondria, whereas older hyphal compartments near the parent cells were vacuolated and possessed small, peripherally located mitochondria . The vacuolated hyphal compartments resynthesized cytoplasm before producing branches and contained giant mitochondria . The cytological model for germ tube formation and hyphal growth proposed by Gow and Gooday (1984) is discussed.

Microbios, 1989, 60(243), 71 - 7
The improved recovery of Candida albicans from fluid culture media; Reeder JC et al.; This study compares the mean generation time (MGT) and lag period of the growth of Candida albicans in four blood culture media, under a variety of conditions of incubation . The media compared were Bactec 6B, brain-heart infusion, malt extract broth and Sabourauds liquid medium . All four media were incubated under the eight possible permutations of the following conditions: 37 degrees C or 30 degrees C, vented or unvented, unshaken or constantly shaken . Then, using the incubation conditions found to be most favourable, minimum detection times for C . albicans were compared in the four media . The combination of incubation of the cultures at 37 degrees C, venting and constant-shaking, produced the fastest generation time with the minimum lag period . Of the media, Bactec 6B medium had the shortest lag period under these conditions while brain-heart infusion had the lowest MGT overall . Sabourauds liquid medium, which resulted in the most favourable combination of generation time and lag period, proved superior to the other media for the recovery of C . albicans.

Curr Top Med Mycol, 1989, 3, 86 - 108
Pathogenesis of Candida vulvovaginitis; Sobel JD; PIP: The occurrence of candida vulvovaginitis (CVV) has been estimated based on statistical data from Great Britain to be an increase to 200/100,000 over 10 years to 1984 . CVV in the US is the 2nd commonest cause of vaginal infection, with bacterial vaginosis occurring twice as often . 85-90% of the yeasts isolated from the vagina are candida albicans, based on biotyping rather that the newer methods of DNA hybridization . The pathogenesis of CVV is discussed in terms of the microbiology (virulence factors, adherence, germ tube and mycelium formation, proteinase secretion, and switching colonies), asymptomatic vaginal colonization, transformation to symptomatic vaginitis, host predisposing factors (pregnancy, oral contraceptives, diabetes mellitus, antimicrobes, and other), vaginal defense mechanisms (humoral system, phagocytic system, cell mediated immunity, vaginal flora, other), and pathogenesis of recurrent and chronic CVV (internal reservoir, sexual transmission, vaginal relapse, and experimental models) The discussion of the development of virulent symptoms is capsuled in the following comments . Vaginal cell receptivity varies among individuals, but all strains of C . Albicans adhere to both exfoliated vaginal and buccal epithelial cells, or mucosal surfaces, through the yeast surface mannoprotein . It is suggested from in vitro studies that germ tube and mycelium formation facilitates vaginal mucosal invasion . Exogenous and endogenous factors may enhance germination and precipitate symptomatic vaginitis, or inhibit germination . Increased proteinase secretion may be a result of the transformation from the blastoconidium/colonization phase to the germinated invasive vaginitis stage or an independent virulence factor . It is reported that hereditable spontaneous switching may occur spontaneously in vivo also . Colonizing yeasts with a change in environment can transform to a more virulent phase . Colonization rates vary from 10-25%, and the critical issue is understanding the process of asymptomatic colonization to symptomatic vaginitis, which is unclear . Inflammation may be caused by direct hyphal invasion or inducing symptoms of allergic reaction without identification of a specific event . Precipitating factors are pregnancy, where estrogens enhance yeast mycelium formation, or high levels of reproductive hormones . High oral contraceptive use is related to the presence of candida as well as uncontrolled diabetes, during or following use of antimicrobial agents, and use of poorly ventilated clothing .

Int Arch Allergy Appl Immunol, 1989, 90(3), 291 - 6
Direct modulation of human neutrophil behaviour by Candida albicans; Vuddhakul V et al.; We examined the direct effect of unopsonized yeast particles of Candida albicans on two aspects of neutrophil behaviour, namely adherence and 3H-deoxyglucose uptake . The data show that brief exposure of C . albicans to human neutrophils resulted in decreased ability of the neutrophils to adhere to Dacron fibre and take up deoxyglucose . This inhibitory effect was further shown to be dependent on yeast concentration and on the integrity of the yeast cell wall . Additional experiments indicate that this effect was direct rather than indirect through soluble mediators in the supernatant . Interference experiments with glucan and mannan, the two major polysaccharide components of the yeast cell wall, suggest that the ligand in direct interaction between C . albicans and neutrophil contains glucan . Finally, it was shown that nonpathogenic species of Candida such as C . krusei, C . parapsilosis and C . guilliermondii did not display neutrophil-modulatory properties while the occasionally pathogenic C . tropicalis did . These results indicate that C . albicans has the ability to circumvent neutrophil defence mechanisms, and may in part explain the propensity of this fungus to cause infection.

Microbiol Immunol, 1989, 33(9), 709 - 19
A role of secreted proteinase of Candida albicans for the invasion of chick chorio-allantoic membrane; Kobayashi I et al.; The invasion of Candida albicans strains into the chorio-allantoic membrane (CAM) of a developing chick was studied by light and electron microscopy . A proteinase-producing strain, NUM961, invaded into intact CAM, but proteinase-deficient strain NUM678 cells remained on the surface of the CAM with no evidence of damage to the host cells . However, NUM678 cells invaded into the ectoderm-damaged CAM, or proteinase-treated one . Electron microscopy revealed that treatment with purified Candida proteinase disorganized the ectoderm tissue by disrupting the intercellular junctions . These results suggest that Candida proteinase damages the CAM surface, which enables the invasion of the growing hyphae.

Ann Otolaryngol Chir Cervicofac, 1989, 106(6), 334 - 7
{Mycotic osteitis of the facial bones . A review of the literature apropos of a case}; Camuzard JF et al.; The authors report a case of mycotic osteitis of the upper maxillary bone due to Candida Albicans occurring in a 56 year old female patient under treatment for chronic myeloid leukemia . The etiologically difficult diagnosis could only be confirmed after deep surgical biopsy with mycological study of a fragment . A review of the literature confirmed the rarity of upper maxillary involvement by Candida Albicans . Particularly when there is isolated involvement and no evidence of a distant primary focus . The differential diagnosis essentially includes centro-facial malignant granuloma.

Int Arch Allergy Appl Immunol, 1989, 90(1), 61 - 6
Allergenic variability of different strains of Candida albicans; Savolainen J et al.; The allergenic variation of six Candida albicans strains was studied by immunoblotting with pooled sera from 20 C . albicans-RAST-positive subjects . The presence of a 46-kilodalton (kD) protein, the major allergen, and a 29-kD protein, an intermediate allergen, was shown in crude extracts from disrupted cells (six strains) . There was a significant variation in the content of the major C . albicans allergen (46 kD) between the different strains . Surface extracts of all six C . albicans strains contained mannan . Immunoblotting of cell wall extracts of intact C . albicans (agar plate) of different age revealed the strongest IgE binding in cultures incubated for 36-50 h . Due to the varying proportions of allergens demonstrated in the different strains of C . albicans, the starting source material for extract production should be a pool of individual strains, which all should be analysed prior to pooling . Special attention should be paid to the selection of C . albicans strains, and a parameter such as the breakability of the strain should be considered.

Arch Dermatol Res, 1989, 281(5), 342 - 5
Correlation between culture medium pH, extracellular proteinase activity, and cell growth of Candida albicans in insoluble stratum corneum-supplemented media; Tsuboi R et al.; Candida albicans produces a major extracellular proteinase whose activities are observed only in weakly acidic pH . However, in affected lesions, a variety of pH conditions exist, including neutral pH . To verify the pathological importance of the extracellular proteinase, the correlation between culture medium pH, extracellular proteinase activity, and cell growth of C . albicans was followed for 3 weeks with unbuffered and insoluble stratum corneum-supplemented liquid media . Each medium pH, initially adjusted within a range of pH 3-7 by the addition of sodium hydroxide or hydrochloric acid solution, was acidified, and a subsequent high proteolytic activity and rapid fungal growth were observed . After full fungal growth, neutralization of each medium to pH 7 and reduction of proteinase activity occurred . Results from a glucose addition experiment suggest that acidification of each medium was produced by the acid formation from glucose and neutralization by the exhaustion of glucose and increase of ammonia from denatured stratum corneum . These data suggest that extracellular proteinase from C . albicans could act as a virulence factor under a wide range of pH conditions by the acidification of the environmental pH close to the organism.

J Med Vet Mycol, 1989, 27(4), 229 - 41
Adansonian study of Candida albicans: intraspecific homogeneity excepting C . stellatoidea strains; Kamiyama A et al.; Fifty-six strains of Candida albicans (40 fresh human isolates, 10 laboratory strains, and 6 Candida stellatoidea strains), seven strains of other Candida species, and one strain of Saccharomyces cerevisiae were examined for a total of 182 biochemical and physiological characters . As 121 characters proved positive or negative in all of the strains, analysis of similarity values (simple matching coefficients) derived from the remaining 61 characters revealed that C . albicans strains could be discriminated from other species with similarity values of 70% or lower, and that the cluster of C . albicans strains with internal similarity values above 70% could be divided into two subclusters representing classical C . albicans and C . stellatoidea, with intergroup similarity of 70 to 85% and intragroup similarities of 85% or higher . No discernible difference was noted between isolates from pathological specimens and those from healthy individuals.

Fortschr Ophthalmol, 1989, 86(4), 323 - 6
{Specificity of the humoral immune response to Candida albicans in patients with panuveitis}; Damms T et al.; Sera from 54 patients with panuveitis and 99 healthy blood donors were tested with an immunoblot assay for antibodies to 11 cytoplasmatic antigens of Candida albicans . In patients with panuveitis, IgG and IgM antibodies to a greater variety of Candida antigens were detected than in blood donors (t test, p = 0.005) . Additionally, IgG antibodies to a 160-kDa protein and a 43-kDa protein, as well as IgM antibodies to the 160-kDa protein and a 67-kDa protein, were recognized more frequently in the sera of patients with panuveitis than in the sera of blood donors (U test, p = 0.05) . These results suggest that in comparison to blood donors, patients with panuveitis have an altered immune response to Candida albicans.

Med Dosw Mikrobiol, 1989, 41(1), 67 - 70
{Effect of synthetic antifungal drugs on the adherence of Candida albicans to the mouth mucosa epithelium in vitro}; Macura AB et al.; Ten Candida albicans strains were tested for their adherence to buccal epithelial cells in vitro in the presence of synthetic antimycotic drugs as 5-fluorocytosine, clotrimazole and ketoconazole . The drugs when applied in therapeutic concentrations inhibited adherence stronger than when applied in subinhibitory concentrations although in both situations the inhibition was statistically significant in comparison to control experiments without these drugs (p less than 0.01) . The highest inhibition of adherence was seen with 5-fluorocytosine and the weakest with clotrimazole . Out of imidazole derived drugs strong inhibition of adherence was achieved with ketoconazole.

Med Dosw Mikrobiol, 1989, 41(1), 53 - 9
{Evaluation of the effect of a new polyfungin derivative in chronic infection of albino mice with P-32 labeled Candida albicans}; Kurnatowska A et al.; White mice, Balb/c, were infected intraperitoneally with Candida albicans strains: standard ATCC 1023 and 910 strain isolated from vaginal excretions of patient suffering from genital mycosis . One group of animals was given new Polish polyene antibiotic N-methylglucamine salt of N-glucosylpolyfungin (N-MGP) . It was possible to follow a course of infection using our own experimental model of candidiasis with 32P-Candida albicans cell suspension by measuring a degree of radioactivity of organs taken from treated and untreated animals . Statistically significant lower radioactivity values (P less than 0.01) were found in organs of animals treated with N-MGP salt for 20 days in daily dose of 20 mg/kg of body weight . Therapeutic efficacy of N-MGP salt was confirmed in separate experiments where mice were infected intraperitoneally with unlabelled Candida albicans cells . Negative results of mycological examinations were found when several organs homogenates of treated mice were tested . Activity of new polifungin derivative in chronic candidiasis of mice was found using two different ways of evaluation of this new preparation.

Dermatol Monatsschr, 1989, 175(6), 326 - 32
Enhancing effect of whole-body ultraviolet light irradiation on Candida albicans activity of human polymorphonuclear leukocytes; Hunyadi J et al.; In an irradiation dose-dependent manner, the whole-body ultraviolet irradiation of healthy volunteers enhances the Candida albicans killing activity of the circulating polymorphonuclear granulocytes . This enhancing effect can be inhibited by oral indomethacine treatment . The sera of the irradiated subjects enhances the killing activity of the granulocytes of untreated individuals . This transfer can be blocked through the administration to the system of ginkgolide B, a competitive antagonist of the platelet activating factor.

Chemotherapy, 1989, 35(2), 130 - 2
Studies on antifungal agents . 20 . Effect of the nitrogen substitution on the in vitro activity of novel 3,5-substituted isoxazolidines; Swift PA et al.; The effect of the nitrogen substitution on the in vitro antifungal activity of a series of novel cis-3,5-substituted isoxazolidine derivatives is investigated . The 2-(N-methyl) analogues 4-6 were found to be the most active compounds when tested in vitro against Trichophyton rubrum, Aspergillus fumigatus and Candida albicans, with MIC values ranging between 0.7 and 70 micrograms/ml.

J Med Vet Mycol, 1989, 27(1), 57 - 8
Vaginal eosinophils and IgE antibodies to Candida albicans in women with recurrent vaginitis; Witkin SS et al.; Eosinophils were identified in 31 of 121 (25.6%) vaginal smears obtained from women with recurrent vaginitis . The presence of eosinophils correlated (p less than 0.005) with the occurrence of IgE antibodies to Candida albicans in vaginal fluid . Localized allergic responses to C . albicans or other allergens may contribute to the pathogenesis of recurrent vaginitis in sensitized women.

J Med Vet Mycol, 1989, 27(1), 51 - 5
Systemic candidosis in beige mice; Baghian A et al.; Systemic spread of Candida albicans after intravenous inoculation was compared in beige mice and their functionally normal littermates . The number of colony forming units (c.f.u.) recovered from the kidneys, livers, and spleens of beige mice was substantially greater (100 to 1000-fold) than the number cultured from the respective organs of their functionally normal littermates . Pre-treatment with silica did not alter the number of c.f.u . recovered from the organs of either beige mice or their normal littermates . These results are consistent with the hypothesis that normally functioning polymorphonuclear leukocytes are crucial to the innate defenses that control the proliferation of this fungus.

J Med Vet Mycol, 1989, 27(2), 121 - 5
A Candida albicans mutant conditionally defective in sterol 14 alpha-demethylation; Shimokawa O et al.; A conditional sterol 14 alpha-demethylation mutant of Candida albicans was isolated whose defect was dependent both on the growth temperature and on the culture medium used . Under restrictive conditions, this mutant showed a deficiency in hyphal growth and an increased susceptibility to diverse chemicals, in accordance with the phenotypes of the already known non-conditional mutants of 14 alpha-demethylation . In addition, the mutant was shown to have a conditional defect in respiration . The impaired respiration was also seen in the non-conditional mutants.

J Antimicrob Chemother, 1989 Jan, 23(1), 87 - 94
Effect of antimicrobial and antineoplastic drugs alone and in combination on the phagocytic and candidacidal function of human polymorphonuclear leucocytes; Pallister CJ et al.; Four antimicrobial and three antineoplastic drugs were screened for their effects on phagocytosis and killing of Candida albicans blastospores by human neutrophil polymorphonuclear leucocytes . Amphotericin B caused significant impairment of both phagocytosis and killing, but cefuroxime and ketoconazole had no effect . Tobramycin did not affect phagocytosis, but impaired killing . Methotrexate, prednisolone and vinblastine all caused significant impairment of phagocytosis, but did not affect killing . Combinations of these seven drugs, such as are used in the treatment of acute lymphoblastic leukaemia in childhood, were also shown to inhibit phagocytosis, although no additive effects were detected . None of the drug combinations tested affected killing.

J Antimicrob Chemother, 1989 Jan, 23(1), 7 - 19
Correlation of inhibition of sterol synthesis with growth-inhibitory action of imidazole antimycotics in Candida albicans; Nicholas RO et al.; The effect of tioconazole and other imidazole antimycotics on both growth and sterol biosynthesis by Candida albicans and C . pseudotropicalis in tube culture was investigated . Trailing endpoints were only seen in statically incubated cultures, but the final MIC, i.e . that giving complete inhibition of growth, was similar in both static and shaken cultures . Desmethylsterol biosynthesis was equally sensitive to the inhibitory action of tioconazole in both shaken and static cultures and the trailing endpoints in the latter coincided with this inhibition . Poor inhibitors of ergosterol biosynthesis did not show the trailing phenomenon but did show a conventional MIC . The inhibition of sterol biosynthesis, unlike that of growth, was not subject to an inoculum effect . As others have found, ergosterol was unable to antagonize the effects of tioconazole on C . albicans and this was probably due to lack of uptake of this sterol . In contrast to C . albicans, the Gram-positive bacterium, Staphylococcus aureus H, which lacks membrane sterols, showed no trailing endpoints with tioconazole after either shaken or static incubation.

Mycopathologia, 1989 Jan, 105(1), 39 - 43
Anaerobically induced production of hybrid monokaryons by heterokaryons of Candida albicans; Sarachek A; During aerobic replication, balanced heterokaryons (hets) of Candida albicans produced by fusing protoplasts of complementing auxotrophic strains characteristically segregate low frequencies of prototrophic monokaryons bearing hybrid nuclei formed either through karyogamy or unidirectional internuclear genetic transfers within het cells . Anaerobic growth causes exponential inactivation of hets and induces their production of hybrid monokaryons . Both responses are functions of heterokaryosis as such and not the genetic backgrounds of hets . Evidence is presented that (i) the nuclei of anaerobically generated hybrids arise through induction in hets of karyogamy not internuclear genetic transfers and that (ii) the events underlying that induction are different from those responsible for inactivation of the cells.

Microbios, 1989, 57(231), 73 - 83
Identification of envelope proteins of Candida albicans by vectorial iodination; Molloy C et al.; Intact Candida albicans yeast cells were radiolabelled with 125I, and cell wall, mixed membrane and soluble fractions prepared . The majority (67%) of the 125I was detected in the protein of the cell wall fraction at a specific activity 70-fold higher than that in the membrane or soluble fractions . SDS treatment of the cell wall fraction released 52% of the total protein but only 3% of the wall-bound 125I, and the extract was shown to be severely contaminated with cytosolic and membrane proteins . Zymolyase digestion of SDS treated walls liberated material which contained 93% of the 125I and on electrophoresis migrated as a single diffuse zone (average Mr 260 kD) typical of heterogenous mannoproteins . Protein (1.5%), GlcN (0.08%) and hexose (98.4%) content was measured and amino acid analysis showed enrichment in Ser (15.9%) and Thr (20.2%) . These results indicate that the major iodinated protein(s) in the cell envelope is a 260 kD mannoprotein fraction containing both O-linked and Asn-linked oligosaccharides.

Scand J Infect Dis, 1989, 21(2), 205 - 12
Surveillance tests for the diagnosis of invasive fungal infections in bone marrow transplant recipients; Tollemar J et al.; A system for serial surveillance cultures and serological tests for diagnosis of disseminated fungal infections (FI) was evaluated retrospectively in 14 bone marrow transplantation (BMT) patients with autopsy proven FI (11 with Candida albicans and 3 with Aspergillus fumigatus) and 14 control BMT patients without FI . The 2 groups did not differ with regard to clinical features . Serial cultures for candida from various sites were more often positive in the FI group than in the controls (p less than 0.001) . Consistently negative cultures were never seen in the FI patients (p less than 0.05) . Positive conventional blood cultures or cultures of specimens from bronchoscopy were suggestive of FI before death in 6/14 of the patients with FI . No blood cultures were positive among the controls . Sequential serum samples taken before death in 7 patients with systemic candidiasis, 3 with invasive aspergillosis, and 12 control patients, were tested retrospectively for diagnostic candida and aspergillus antibody titers and free circulating candida mannan . The serological tests gave evidence of FI in 9/10 patients with FI and in half of the controls (p less than 0.05) . In 8/10 cases with FI, serological tests became positive before a positive blood culture or a clinical suspicion of FI . With a prevalence of 7.5% of FI at our clinic, the predictive values for positive and negative was 100% and 97% for the antigenemia test and 14% and 100% for the ELISA test for IgA antibody against C . albicans mannan . Our data suggest that a rational use of surveillance cultures and serological tests may aid in an earlier diagnosis of FI in BMT patients.

Scand J Infect Dis, 1989, 21(1), 113 - 5
Septic pulmonary embolism caused by Candida albicans: a fatal complication to bone marrow transplantation; Kronborg G; A fatal course of Candida albicans infected embolism in a 31-year-old woman undergoing bone marrow transplantation due to leukemia is described . C . albicans was continuously cultured from the mucous membranes for 6-8 months after transplantation in spite of local treatment with amphotericin B and mycostatin and systemic treatment with itraconazole.

Chemotherapy, 1989, 35(1), 39 - 42
Studies on antifungal agents . 19 . Effect of the C-5-aromatic substitution on the in vitro activity of novel 3,5-substituted isoxazolidines; Mullen GB et al.; The influence of the C-5-aromatic substitution on the in vitro antifungal activity of novel cis-3,5-substituted isoxazolidine derivatives was investigated . Compounds having a C-5-(substituted phenoxy)methyl group were found to be the most active against Trichophyton rubrum, Aspergillus fumigatus and Candida albicans with MIC values ranging from 0.7 to 70.0 micrograms/ml . Replacing the phenoxymethyl group with either naphthyl or 2-oxo-1,3-benzoxathiol-6-yl groups resulted in a diminished in vitro activity.

Arch Microbiol, 1989, 151(2), 149 - 53
Changes in internal and external pH accompanying growth of Candida albicans: studies of non-dimorphic variants; Stewart E et al.; Non-dimorphic variants of Candida albicans, which were unable to form germ tubes or mature hyphae in media containing amino acids, glucose and salts or N-acetylglucosamine or serum, were prepared from two hyphal positive laboratory strains using a physical separation method . The hyphal-minus phenotype was stable and may be due to mutations or phenotypic variation . The variant strains maintained their internal pH within narrower bounds as compared to their parental wild-types . When exposed to conditions that normally supported the induction of germ tubes the cytoplasmic pH of the wild type strains increased from 6.8 to over pH 8.0 within 5 min while in the variants the rise in internal pH was only about 0.3 pH units . The wild type strains acidified the growth medium more rapidly than the variants . The results suggest that the control of internal pH is directly or indirectly associated with the regulation of dimorphism . The variants had unaltered cell volumes and specific growth rates . The hyphal-minus phenotype was however fully reversible since revertants occurred spontaneously on serum containing agar.

Antimicrob Agents Chemother, 1989 Jan, 33(1), 16 - 8
Effect of attachment of anticandidal antibody to the surfaces of liposomes encapsulating amphotericin B in the treatment of murine candidiasis; Hospenthal DR et al.; The effect produced by antibody specific to Candida albicans when attached to liposomes containing amphotericin B was studied in vivo . Liposomal amphotericin B bearing specific immunoglobulin (LAMB-Ab) was compared with the unencapsulated drug (fAMB) and other liposomal amphotericin B formulations in the short-term survival (21 days) of mice with disseminated candidiasis . Both the treatment and prophylaxis of the murine model of candidiasis were explored in these trials . LAMB-Ab increased survival rates in the model more than other liposomal preparations containing amphotericin B . Liposomal amphotericin B compounds as a group prolonged survival over fAMB . Liposomal preparations used for comparison included liposomes with attached nonspecific antibody (LAMB-Ab-), liposomes without antibody (LAMB), and liposomes with unattached specific antibody (LAMB+).

Kekkaku, 1989 Jan, 64(1), 7 - 13
{Pulmonary tuberculosis and mycotic infection--clinical and serological diagnosis}; Iwata H et al.; The antibody activities against Aspergillus fumigatus and Candida albicans by indirect hemagglutination (IHA) and counterimmunoelectrophoresis (CIE) were examined twice at a month's interval in 251 sera from 169 male and 82 female patients admitted to the Higashi Nagoya National Hospital for pulmonary diseases . The patient population was composed of 226 patients with active or cured pulmonary tuberculosis including 25 patients complicated with pulmonary aspergillosis and 25 other lung diseases . In our tests, antigens used were crude supernatants of culture-broth which are the generous gifts of Torii Pharmaceutical Company . The antibody activity against Aspergillus by IHA was positive in 2.9% of the sera in the first and in 0.9% in the second test and was positive against Candida by IHA in 44.9% in the first and in 44.0% in the second test (Table 1) . As regards patients with pulmonary tuberculosis, the population whose serological reaction was positive against Candida did not increase with age (Table 2) . Two results of the antibody activities against Aspergillus and Candida by CIE were the same . The CIE results were positive in 19.5% against Aspergillus and in 16.3% against Candida (Table 3) . In CIE test, 4.3% were positive against both Aspergillus and Candida . The causes of high positive rate in IHA against Candida may be due to (1) difference in the antibody, namely, antibody measured by IHA mainly composed of IgM and that by CIE composed of IgG and (2) difference in the virulence between Candida and Aspergillus.(ABSTRACT TRUNCATED AT 250 WORDS)

Rev Fr Gynecol Obstet, 1989 Jan, 84(1), 45 - 6
{Spontaneous abortion with an IUD and Candida chorioamnionitis}; Michaud P et al.; Interruption and expulsion of a stillborn fetus in patients with an IUD Candida albicans chorioamniotic infection is a very rare obstetrical event . Generally, the diagnosis is established in retrospect by the routine histological examination of the products of expulsion and the demonstration of a specific chorioamniotic infection . This infection occurs by upward dissemination in a pregnancy where the amniotic membrane is unbroken, with the IUD being the facilitating factor of infection . Prevention appears to be the withdrawal of an IUD at the beginning of pregnancy.

Eur J Obstet Gynecol Reprod Biol, 1989 Jan, 30(1), 67 - 72
Premature ovarian failure . II: Considerations of cellular immunity defects; Mignot MH et al.; Twenty-three patients with premature ovarian failure (POF), were investigated on the basis of cell-mediated immunity . An increase in T-cells and especially T-helper cells was found in the group of POF patients, while T-suppressor cells and B-cells did not exceed the counts compared to healthy controls matched for age and sex . The macrophage migration inhibition factor (MIF) assay showed a decreased activity towards Haemophiles influenza . Candida albicans and Varidase antigens in the POF group . Levels of immunoglobulins (IgG, IgA, IgE and IgM) did not exceed the normal levels . The relationship between the hormonal status of POF patients and their immunological profile is discussed.

J Forensic Sci, 1989 Jan, 34(1), 105 - 9
The effect of temperature on the formation of ethanol by Candida albicans in blood; Chang J et al.; The effect of temperature on microbial fermentation in blood was studied . Specimens of human blood from a blood bank were inoculated with Candida albicans, an organism capable of causing fermentation . A preservative was added to a portion of the inoculated specimens . These inoculated specimens, as well as uninoculated blood, were stored under various temperature conditions . Production of ethyl alcohol was monitored over a period of six months . Fermentation was found to be highly temperature dependent, with refrigeration proving to be most effective at inhibiting ethanol formation.

Ann Allergy, 1989 Jan, 62(1), 15 - 20
Immunologic analysis of steroid-dependent asthma; Ito K et al.; In order to analyze steroid-dependent asthma immunologically, IgE antibodies to mite (Dermatophagoides farinae), Candida albicans, and Aspergillus fumigatus were measured in 112 asthmatic patients . IgG and IgG subclass antibodies to mite were also measured . The rate of patients who were positive to candida IgE RAST was higher in atopic steroid-dependent patients than in atopic steroid-independent patients (P less than .01) . The rate of mite-sensitive patients who had not received immunotherapy with mite or house dust was higher than in the atopic steroid-dependent patients than in atopic steroid-independent patients (P less than .05) . IgG1 and IgG4 antibodies to mite were higher in mite-sensitive steroid-independent patients than in mite-sensitive steroid-dependent patients . IgE antibodies to A . fumigatus were detected only in patients with allergic bronchopulmonary aspergillosis (ABPA) . Based on these results, we were encouraged to try immunotherapy with house dust mite or C . albicans if patients were steroid-dependent and sensitive to these allergens except when the patients had ABPA.

Mycoses, 1989, 32 Suppl 2, 9 - 11
Incidence of oral candidosis; Meinhof W et al.; Although it is well known that both yeasts in general and Candida albicans in particular are frequently found in the oral cavity of ill and even of healthy individuals, the definite incidence of oral candidosis is far from being clear . Today it is, however, possible to assess the frequency of oral candidosis in a country indirectly, judging from the frequency of prescription of drugs for this indication . Data thus obtained indicate a remarkable increase of the frequency of the disease during the last decade . While polyenes are still prescribed for oral candidosis about as often as ever, the prescription of azoles has gained more and more importance.

J Med Vet Mycol, 1989, 27(6), 363 - 80
Gastrointestinal and systemic candidosis in immunocompromised mice; Cole GT et al.; Oral-intragastric inoculation of 6-day-old outbred Crl:CFW(SW) BR mice with Candida albicans can lead to colonization of the gastrointestinal (GI) tract . We have shown that in the absence of an immunocompromising treatment, Candida is primarily localized in the stomach and intestines of mice at 20 days post-inoculation . Cultures of homogenates of the esophagus of most animals tested, and homogenates of the liver, lungs, spleen and kidneys of all animals tested, proved negative for C . albicans . Previous histological examinations of the GI tract of these colonized, non-immunocompromised mice showed hyphal elements associated with the stratified, squamous epithelium of the stomach in the region of the cardial-atrium fold . In this study, mice were immunocompromised by intraperitoneal injection of cyclophosphamide and cortisone acetate 11-14 days after oral-intragastric challenge with C . albicans and then sacrificed 20 days post-challenge . A high density of invasive hyphae was observed in the same, cardial-atrium region of the stomach of these animals . Cultures of the homogenized stomach showed a 100-fold increase in colony forming units (c.f.u.) of C . albicans compared with stomach homogenates of infected but non-immunocompromised controls . In addition, homogenates of the esophagus and selected body organs of most immunocompromised mice examined were positive for C . albicans by plate culture . When the immunocompromising drug treatment was delayed 3-5 weeks after oral-intragastric challenge, proliferation of C . albicans in the stomach and intestines was still evident, although fewer mice showed systemic spread and lower numbers of c.f.u . were recovered from body organ homogenates . Abscesses which contained both C . albicans hyphae and yeast cells were frequently observed in the liver and occasionally in the lungs and kidneys of immunocompromised mice sacrificed 20 days post-inoculation . The frequent occurrence of abscesses in the liver simulates a clinical variant of this mycosis, referred to as focal hepatic candidosis, which has been recognized with increasing frequency in immunocompromised patients . We suggest that the animal model described here may be particularly useful both for exploring methods which may prevent dissemination of C . albicans from localized foci of colonization in the GI tract after exposure of the host to immunocompromising drugs, and for testing the efficacy of anti-Candida drugs in clearance of the pathogen from body organs with established fungal abscesses.

Urol Res, 1989, 17(6), 367 - 70
Renal candidiasis in the rat: effects of ureteral obstruction and diabetes; Tarry WF et al.; The effect of ureteral obstruction on the course of renal candidiasis in a rat model was studied, using both normal and diabetic Sprague-Dawley rats, and a clinical isolate of Candida albicans . Diabetes was induced by streptozotocin injection 1 week prior to inoculation and transabdominal ligation of the left ureter . On day 9 post inoculation, mean titers of Candida were similar in right and left kidneys of obstructed rats . Mean left renal titers for obstructed and control rats were similar (log10 2.68 CFU/g +/- 0.73 (SE) vs . log10 2.21 +/- 0.09, P greater than 0.01) . Diabetes produced higher renal titers of Candida, regardless of the presence of ureteral obstruction (log10 5.74 CFU/g +/- 0.57 (SE) vs . log10 2.21 +/- 0.09, P less than 0.01) . Animals treated for one week with amphotericin B showed a marked difference in Candida titers between obstructed and control animals (log10 4.14 CFU/g +/- 0.45 (SE) vs . 1.57 +/- 0.38) for both kidneys, and between obstructed and nonobstructed kidneys in the same animals.

Drugs Exp Clin Res, 1989, 15(8), 335 - 47
In vivo activity and metabolic fate of 2-(2,3,3-triiodoallyl)tetrazole (ME1401), a novel antifungal agent; Fukuyasu H et al.; 2-(2,3,3-Triiodoallyl)tetrazole (ME1401), a novel antifungal agent, showed therapeutic effectiveness in topical treatment of experimental dermal infections with Trichophyton mentagrophytes and Candida albicans in guinea-pigs . Addition of diethyl sebacate to the ME1401 preparations increased its in vivo antifungal activity and its penetration into the skin . When the estimation of efficacy of treatment with active formulations was made on the basis of skin lesion and the rate of negative skin cultures in comparison with those for infected, untreated or placebo-treated controls, the in vivo activity of 0.5% ethanol tincture or gel of ME1401 was comparable to that of reference antimycotic drugs such as clotrimazole, haloprogin and others . Pharmacokinetic studies in the experimental animals demonstrated that ME1401 was unstable in vivo, being readily converted to an active metabolite 2-(3-iodopropargyl)tetrazole (CN144) first and then to 2-propargyltetrazole (CN151) . CN144 showed potent in vitro and in vivo antifungal activities, while the in vitro activity of CN151 was negligible.

Cancer Chemother Pharmacol, 1989, 25(1), 75 - 6
Herpes simplex virus, Candida albicans and mouth ulcers in neutropenic patients with non-haematological malignancy; Beattie G et al.; Mouth ulcers are a frequent cause of morbidity in patients rendered neutropenic as a result of chemotherapy . We report here a series of 28 such patients from whom swabs were taken for viral isolation and mycological culture . In 13 patients, herpes simplex virus (type I) was isolated and in 17 patients Candida albicans was cultured . Both organisms were isolated in 9 patients . Our results suggest that both a viral and fungal element may be important in the aetiology of oral ulceration and that antiviral and antifungal agents may each have a role in the prophylaxis and treatment of such patients.

Scand J Infect Dis, 1989, 21(5), 557 - 61
Yeasts in blood cultures: impact of early therapy; Rantala A et al.; Patients with growth of yeast in blood cultures were analyzed during the 6-year-period 1981-1986, with special regard to predisposing factors, mortality, severity of the disease and therapy . There were 80 isolations of yeasts in blood cultures in 39 patients and Candida albicans was the most common . The majority of the patients in the material had multiple predisposing factors . The overall mortality was 58% . Patients with d disseminated disease had a mortality of 79% in contrast to 32% in patients with transient fungemia . Disseminated disease was more common in surgical patients . The prognosis of patients treated within 4 days from the onset of septic symptoms was significantly better than that of patients with a later start of therapy . On the basis of these results we emphasize the importance of early empiric therapy.

J Med Vet Mycol, 1989, 27(6), 431 - 4
The identification of Candida albicans strains by restriction fragment length polymorphism analysis of DNA; Smith RA et al.; Digestion of total DNA from Candida albicans isolates with the restriction enzyme HinfI generated simple, readily interpretable band patterns on ethidium bromide-stained gels . The procedure, which was highly reproducible, was used to detect restriction fragment length polymorphisms in 47 isolates of this species.

Scand J Infect Dis, 1989, 21(6), 633 - 43
Prognostic value of immunologic abnormalities and HIV antigenemia in asymptomatic HIV-infected individuals: proposal of immunologic staging; Hofmann B et al.; The prognostic value of various immunologic tests was investigated in 150 HIV-seropositive homosexual men, who were initially without HIV-related symptoms or AIDS and who were followed for a median of 12 months (range 3-28 months) . The laboratory investigations included HIV antigen in serum, total lymphocyte count, T-helper (CD4) and T-cytotoxic/suppressor (CD8) counts, and lymphocyte transformation responses to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM), and to antigenic extracts from Candida albicans and cytomegalovirus . 24 individuals developed HIV-related symptoms or AIDS (11 cases) . All parameters except the CD8 count were of prognostic value, but a multivariate analysis of symptom-free survival showed that HIV antigenemia, a CD4 count less than 0.5 x 10(9)/l, and relative response to PWM below 25% of controls contained all the prognostic information . Individuals abnormal at entry for these 3 variables had a theoretical 36 times as high hazard of developing symptoms within the observation period as had individuals with normal parameters . There was no significant covariation between HIV antigenemia on the one hand and CD4 count and response to PWM on the other . Although, the latter 2 variables covaried, each of them provided independent information, and both were used to classify the degree of the immunodeficiency in 3 stages: Im-0 with normal values, Im-1 with one, and Im-2 with both tests abnormal . Individuals in stage Im-2 had a 10 times increased risk of developing symptoms . The immunologic staging correlated significantly with the clinical grouping (CDC criteria) . This staging improved in only 1, but deteriorated in half of 36 individuals observed for at least 18 months . Thus, the staging is likely to prove useful when attempts to arrest the immunodeficiency of HIV-infected individuals has to be monitored.

Fukuoka Shika Daigaku Gakkai Zasshi, 1989, 16(4), 510 - 21
Starvation and germ tube formation in the exponential phase Candida albicans; Cho T et al.; Two chemically defined media were developed for the induction of germ tubes in exponential phase cells of Candida albicans . One medium was N-acetyl-D-glucosamine medium which is composed of L-thiazolidine-4-carboxylic acid, L-proline, NaHCO3, sodium acetate, NaH2PO4 and N-acetyl-D-glucosamine . The other one was glucose medium in which N-acetyl-D-glucosamine is exchanged for glucose plus NH4Cl in N-acetyl-D-glucosamine medium . In these media, a high percentage of germ tube forming cells was obtained without a temperature shift . However, starvation of the cells in water at 37 degrees C was a necessary pretreatment to consistently obtain a high percentage of germ tube forming cells . The effect of starvation was remarkable in glucose medium, the percentages of germ tube forming cells among the normal cells and starved cells were 20 and 80, respectively . As for intracellular changes during starvation, a decrease in adenosine triphosphate concentration and an increase in adenosine 3',5'-cyclic monophosphate concentration were observed.

Med Dosw Mikrobiol, 1989, 41(3-4), 202 - 5
{Effect of itraconazole on the process of mycelial transformation of Candida albicans cells in human serum}; Gwiezdzinski Z et al.; Results of in vitro studies on the influence of itraconazole on mycelial transformation of 88 Candida albicans strains are presented . The drug influenced a number of cells capable to produce filaments . The number of those cells diminished gradually together with the increase of the drug concentration . The range of TI100 values was between 0.02 and 18.0 micrograms ml of medium . Mycelial transformation phenomenon can be applied for preliminary and rapid evaluation of Candida albicans strains sensitivity to itraconazole.

Bull Soc Pathol Exot Filiales, 1989, 82(5), 690 - 3
{Chronic diarrhea and parasitoses in adults suspected of AIDS in the Ivory Coast}; Therizol-Ferly PM et al.; 148 adult patients with chronic diarrhoea and suspected to be HIV infected have had stool examinations . 46 are without any enteric parasite . Those detected in the others patients are Sporozoans: I . belli (16.2%) and Cryptosporidium sp . (6.7%) found alone or joint, together or with other parasites . Among those, all Flagellate species are identified, but T . intestinalis (6%) is predominant . Entamoeba coli (8.%) is the most frequent amebic species, however, E . histolytica histolytica have been found twice, once singly, the second associated with I . belli, Schistosoma mansoni and Candida albicans . Necator americanus (14%) and Strongyloides stercoralis (12%) are the predominant worm species . Among the yeasts, C . albicans (35.8%) is the most important species isolated, singly in 13.5% of the patients . In an intertropical and parasitical endemic area where many parasites are not considered uncommon, opportunist agents as I . belli, Cryptosporidium sp . and C . albicans appear in an non-negligible frequency in our study.

Mycoses, 1989, 32 Suppl 1, 35 - 52
Biochemical approaches to selective antifungal activity . Focus on azole antifungals; Vanden Bossche H et al.; Azole antifungals (e.g . the imidazoles: miconazole, clotrimazole, bifonazole, imazalil, ketoconazole, and the triazoles: diniconazole, triadimenol, propiconazole, fluconazole and itraconazole) inhibit in fungal cells the 14 alpha-demethylation of lanosterol or 24-methylenedihydrolanosterol . The consequent inhibition of ergosterol synthesis originates from binding of the unsubstituted nitrogen (N-3 or N-4) of their imidazole or triazole moiety to the heme iron and from binding of their N-1 substituent to the apoprotein of a cytochrome P-450 (P-450(14)DM) of the endoplasmic reticulum . Great differences in both potency and selectivity are found between the different azole antifungals . For example, after 16h of growth of Candida albicans in medium supplemented with {14C}-acetate and increasing concentrations of itraconazole, 100% inhibition of ergosterol synthesis is achieved at 3 x 10(-8) M . Complete inhibition of this synthesis by fluconazole is obtained at 10(-5) M only . The agrochemical imidazole derivative, imazalil, shows high selectivity, it has almost 80 and 98 times more affinity for the Candida P-450(s) than for those of the piglet testes microsomes and bovine adrenal mitochondria, respectively . However, the topically active imidazole antifungal, bifonazole, has the highest affinity for P-450(s) of the testicular microsomes . The triazole antifungal itraconazole inhibits at 10(-5) M the P-450-dependent aromatase by 17.9, whereas 50% inhibition of this enzyme is obtained at about 7.5 x 10(-6)M of the bistriazole derivative fluconazole . The overall results show that both the affinity for the fungal P-450(14)DM and the selectivity are determined by the nitrogen heterocycle and the hydrophobic N-1 substituent of the azole antifungals . The latter has certainly a greater impact . The presence of a triazole and a long hypdrophobic nonligating portion form the basis for itraconazole's potency and selectivity.

Przegl Dermatol, 1989 Jan-Mar, 76(1), 23 - 7
{In vitro investigations of Candida strains for itraconazole}; Gwiezdzinski Z et al.; Results of studies in vitro of the susceptibility of 102 strains of Candida type (88--Candida albicans, 7--Candida intermedia, 3--Candida parapsilosis, 1--Candida stellatoidea, 3--Torulopsis candida), to itraconazole have been reported . The strains were isolated from lesions of the skin and mucous membranes . The strains tested showed no resistance to this drug . Itraconazole concentrations inhibiting completely the growth of the yeast-like fungi ranged from 0.02 to 35.0 micrograms/ml of a culture medium . Strains of Candida albicans have shown the least susceptibility, most Candida intermedia . Changes in sensitivity (MIC) of some strains of Candida type for itraconazole after 48 and 72-hrs periods of incubation were very little.

Scand J Infect Dis, 1989, 21(3), 245 - 53
Cytomegalovirus the predominant cause of pneumonia in renal transplant patients . A two-year study of pneumonia in renal transplant recipients with evaluation of fiberoptic bronchoscopy; Heurlin N et al.; The microbiological etiology of pneumonia in 34 renal transplant patients with clinical and X-ray evidence of pulmonary parenchymal disease was studied . Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL), transbronchial lung biopsy (TBB) and brushing was performed on 18 patients . Laboratory evaluation included histological and cytological methods, cultures for bacteria, fungus and virus and immunofluorescence techniques for the detection of Pneumocystis carinii, cytomegalovirus (CMV) and legionella . Serum samples were obtained concomitantly for antibody studies . CMV, the most common etiology, was considered to be the cause of disease in 18/34 patients . All but one of these patients had positive CMV isolates in culture on leucocytes . Pulmonary edema was found in 7 patients, bacterial pneumonia in 11 patients, P . carinii in 4 patients and Candida albicans in 1 patient . Multifactorial etiology was found in 12/34 cases . The overall mortality was 32% . Bronchoscopy gave correct diagnosis in 13/14 patients with infectious pulmonary diseases (93%) . Bronchoscopy procedures were well tolerated and should be considered in transplant patients with evidence of pulmonary parenchymal disease.

J Med Vet Mycol, 1989, 27(2), 63 - 70
A comparison of fluconazole and ketoconazole in the treatment of rat palatal candidosis; Martin MV; The efficacy of fluconazole and ketoconazole in the treatment of rat palatal candidosis has been investigated . To induce oral candidosis, the palatal tissues of Wistar rats were inoculated with Candida albicans NCPF 3091 and covered with acrylic plates . The rats were treated with either fluconazole or ketoconazole by intragastric gavage for 14 days . Palatal epithelial thickness, the number of yeasts present and the histopathological appearance of the tissue were assessed to compare treatment with the two azoles . A fluconazole dose of 0.75 mg kg-1 body weight once daily for 14 days was required to cure the palatal candidosis and prevent recrudescence, whereas with ketoconazole a dose of 7.0 mg kg-1 body weight was necessary to achieve the same effect . From these results it is concluded that fluconazole is effective at a dose nine times lower than ketoconazole in resolving rat palatal candidosis.

Jpn J Antibiot, 1989 Jan, 42(1), 47 - 54
{A clinical evaluation of injectable fluconazole in the treatment of deep mycosis associated with hematological malignancy}; Toyama K et al.; The clinical efficacy and the safety of fluconazole as given at an intravenous dose of 100-400 mg daily were assessed in 7 patients with deep mycosis associated with hematological malignancy . Enrolled in the study were 1 patient with acute lymphatic leukemia, 1 with acute myelocytic leukemia, 2 with acute myelomonocytic leukemia, 2 with malignant lymphoma and 1 with myelodysplastic syndrome . Pathogens isolated from 4 patients were all Candida species including 2 Candida albicans, 1 Candida parapsilosis and 1 Candida krusei . Diagnoses of fungal infections of the patients were Candida pneumonia in 3 patients, candidemia in 1 and fungemia suggested in 3 . Assessment of the clinical efficacy was made on 4 patients from whom pathogens were isolated . The global clinical improvement was good in 2 patients and fair in 1 with Candida pneumonia and good in 1 with candidemia . In the mycological assessment, pathogenic fungi were eradicated in 3 patients and decreased in 1 patient . No significant adverse reactions nor abnormality in clinical laboratory tests related with the dosing of fluconazole were observed in any of the patients.

Acta Univ Palacki Olomuc Fac Med, 1989, 122, 45 - 53
Cell wall of Candida albicans as a factor of pathogenicity; Weigl E et al.; The method of chemiluminiscence monitoring of oxygenous radicals was used for evaluation of human polymorphonuclear leukocytes activated by (1) intact cells of Candida albicans, (2) polysaccharide fraction of C . albicans cell walls . The results indicate that polysaccharide fraction of the cell wall activates the metabolic burst of PMN leukocytes as intact yeast cells and releases oxygenous radicals that play an important role in the origin of inflammatory response . The findings obtained allow to characterize polysaccharide fraction of cell walls as a significant pathogenic feature of C . albicans.

Zahn Mund Kieferheilkd Zentralbl, 1989, 77(4), 312 - 5
{In vitro microbiological research on oral ointments}; Oehring H et al.; Two oral ointments were investigated of their antimicrobial activities using agar diffusion test and suspension method with aerobic germs and Candida albicans . The oral ointment Parodontal-Mundsalbe-neu was better then Parodontal-Mundsalbe-alt with regard to intensity, begin and end of action . In our experiments the field of activity of both ointments against the species tested was identically.

Am J Ind Med, 1989, 15(5), 601 - 5
Dermatoses among poultry slaughterhouse workers; Hayashi M et al.; A survey on the incidence of occupational dermatoses among poultry slaughterhouse workers, who, in order to do their work more efficiently, protected their hands only with cotton gloves, revealed that many workers had dermatoses of the hands . Their symptoms included maceration, erosio interdigitalis, paronychia, trichophytia unguium, and eczema, presumably caused by the constant wetness of their hands during work . Candida albicans was detected in the ungual lesions of some patients . A second survey including a skin examination was performed at a plant where preventive measures such as better working gloves and improved sanitary conditions had been implemented because of the high incidence of skin disorders . The results of this survey showed marked improvement in the reduction of the incidence of dermatoses.

Schweiz Monatsschr Zahnmed, 1989, 99(7), 787 - 90
{The antimicrobial effect of an alginate with an antiseptic admixture}; Setz J et al.; Attempts to simplify impression disinfection lead to the production of an aseptic alginate impression material (Blueprint asept, De Trey/Dentsply, Konstanz, Germany) . This study describes the aseptic properties of this new type of impression material . The in-vitro part of the experiments showed a reduction of Staphylococcus aureus by 6 and of Pseudomonas aeruginosa by 4 log steps after 60 min, and of Candida albicans by at least 3 log steps after 15 min of exposure . Under in-vivo conditions oral bacteria residing on the impression surfaces were reduced by nearly 4 log steps . Although the aseptic properties of the material were demonstrated, the biological acceptance, dimensional stability and compatibility with gypsum have to be tested in further studies.

Mycopathologia, 1989 Jan, 105(1), 25 - 33
Accumulation of acyclic polyols and trehalose as related to growth form and carbohydrate source in the dimorphic fungi Mucor rouxii and Candida albicans; Pfyffer GE et al.; Yeast (Y) and hyphal (H) cells of Mucor rouxii and Candida albicans were cultivated in liquid media containing different carbon nutrient sources (glucose, fructose, ribose) and their free acyclic polyol and trehalose contents determined using capillary gas liquid chromatography (TMS- and OAc-derivatization) . Irrespective of growth form and C-source, the fraction of the water-soluble neutral components of the cellular mass of the cultures - highly homogeneous with regard to the respective cell form produced - contained glycerol, ribitol and arabitol, in addition to trehalose . The polyols contributed 0.5-2% to the biomass of M . rouxii and 1.5-6% to that of C . albicans; the values for trehalose ranged from 0.2-11% in the former and 1-3.5% in the latter species . Mucor contained higher amounts of ribitol and arabitol in H cells and larger quantities of trehalose and glycerol in Y cells . In Candida, too, hyphae always exhibited higher ribitol contents, whereas arabitol attained higher levels in yeasts under almost any conditions - regardless of the type of medium (synthetic vs . complex), stage of culture (early vs . late log-phase) and strain used . Glycerol concentration was not correlated with the growth form; trehalose contents tended to be higher in Y cells . Taking into account the facts that C . albicans and certain Mucor species are agents of opportunistic infections and are invasive mainly in the filamentous form, and that the prospective hosts do not accumulate either of these carbohydrates, the possibility is considered of using trehalose- and polyol-metabolizing enzymes as targets for designing antifungal drugs.

Gen Pharmacol, 1989, 20(2), 151 - 5
Effects of acetylsalicylic acid on the phagocytic function of human polymorphonuclear leukocytes in vitro; Rodriguez AB et al.; 1 . In this paper acetylsalicylic acid (aspirin), an anti inflammatory drug, was studied in vitro at doses of 50, 100, 200 and 500 mg/l to see its effects on adherence, chemotaxis, spontaneous mobility, phagocytosis, candidicide power, nitrobule tetrazolium (NBT) reduction as well as the incorporation and metabolism of arachidonic acid in human polymorphonuclear neutrophils (PMNns) . 2 . Aspirin significantly stimulated neutrophil adherence to nylon fiber at all the doses used, with a correlation between the doses used and the adherence indices found . 3 . At the therapeutic dose (100 mg/l) aspirin brings about a significant increase of chemotaxis, but reduces this property at the highest dose (500 mg/l) . On the other hand, spontaneous mobility is not altered except with the 500 mg/l dose of aspirin which produces a significative decrease . 4 . The ingestion of Candida albicans by PMNns is significant at the therapeutic dose; the candidicide power is not modified with any of the doses used with 100 mg/l of aspirin nitroblue tetrazolium (NBT) reduction is significantly increased . 5 . No changes are observed in the incorporation of arachidonic acid or in the release of its metabolites.

Hum Immunol, 1989 Jan, 24(1), 31 - 9
HLA antigens in ocular tissues . III . Antigen presentation by gamma interferon-treated cultured uveal cells; Abi-Hanna D et al.; In previous studies we have shown that normal human uveal cells, with the exception of vascular endothelium, do not express class I or class II HLA antigens in vivo . Class I antigens are induced in vitro by a variety of cytokines, while class II antigens are only induced by gamma interferon . In this study we examine the capacity of cultured uveal cells, rendered class II HLA antigen positive by gamma interferon, to present antigen to T cells . Cultured uveal cells were found to present antigen (tetanus toxoid, PPD, and Candida albicans) to T cells, but only when they were pretreated with gamma interferon . This function of uveal cells was antigen specific and MHC restricted and was blocked by class II-specific monoclonal antibodies, indicating the crucial role of class II HLA antigens in antigen presentation.

G Batteriol Virol Immunol, 1989 Jan-Dec, 82(1-12), 114 - 20
{Behavior of Candida albicans during a period of nutritional deprivation . Preliminary results}; Bruatto M et al.; Cells of Candida albicans, after 24 hours of growth in YM, were starved, alternatively, in citrate buffer, physiological solution, MMS deprived of glucose or ammonium sulphate . The eventual growth was monitored by determining the absorbance at 675 nm . Simultaneously, the cell morphology was also controlled . In a second series of experiments, the C . albicans cells taken from YM were starved for 72 hours in one of the mediums as stated above, and then reinoculated in MMS liquid without, alternatively, glucose or ammonium sulphate . Again the eventual growth was monitored as in the above method . The achieved results indicate the presence of a reserve of nitrogen, which can be utilized when a source of C is given to the cell . We therefore discuss the apparent lack of glucidic reserve and we propose a method for the consumption of nitrogen reserve . The aim of the work is to define how to obtain cells that contain the smallest amount possible of endogenous reserve.

Pediatr Neurosci, 1989, 15(6), 269 - 75
Neuropathology of pediatric liver transplantation; Hall WA et al.; We reviewed the clinical histories and autopsy records of 35 pediatric patients (ranging in age from 9 months to 18 years) who underwent orthotopic liver transplantation using ciclosporin and corticosteroids for immunosuppression . At the time of death, 19 children (54%) had encephalopathy, 16 (46%) were lethargic or in coma, 10 (29%) had seizures, and 10 were normal . Neuropathological lesions were found on postmortem examination in all 35 patients . Vascular lesions such as infarction, ischemia, thrombosis, and hemorrhage were the most common neuropathological findings (86%) followed by infectious processes (29%) . Candida albicans (2 patients) and Aspergillus fumigatus (3 patients) were the only offending organisms identified, both causing meningoencephalitis . Alzheimer type II astrocytes, a characteristic feature of chronic liver disease, were the single most common autopsy finding (69%) . Central pontine myelinolysis was seen in 3 children and basilar artery thrombosis affected 1 child . Neurological complications and their subsequent neuropathology are a significant cause of morbidity and mortality after pediatric liver transplantation . Vascular insults, electrolyte abnormalities, and infections that involve the central nervous system are directly related to liver function and the immunosuppression necessary to maintain graft viability . Only with continued observation after surgery combined with rapid medical and surgical treatment can we hope to improve the prognosis following liver transplantation in the pediatric population.

Gerodontology, 1989 Winter, 8(4), 101 - 7
Prevalence of Candida albicans in denture wearers in an Israeli geriatric hospital; Cardash HS et al.; Thirty-seven patients wearing complete dentures were investigated for Candida albicans . Twenty-five of the patients suffered from denture stomatitis and twelve had clinically normal mucosa . Candida albicans was isolated and identified from Sabouraud dextrose agar culture medium models constructed from impressions of the maxilla and from the upper dentures . The presence of Candida albicans was demonstrated in all denture wearers suffering from denture stomatitis and in 82% of denture wearers in a control group . A higher concentration of Candida was found in the denture stomatitis group . Large quantities of Candida resided in the denture base and not in the palate . Candida was also found in the denture base in areas not related to the lesion . The concentration of Candida was related to denture cleanliness.

Sel Cancer Ther, 1989, 5(3), 113 - 7
A comparison of in vitro toxicity and antifungal efficacy of membrane-active drugs after liposome encapsulation; Mehta RT et al.; The membrane-active ionophores were observed to possess antifungal activity against Candida albicans 336 and were toxic to human erythrocytes . Liposome encapsulation of these drugs significantly reduced their toxicity to erythrocytes but resulted in the loss of their antifungal potency . These results are compared with membrane-active polyenes which maintained their antifungal activity after encapsulation into liposomes . Liposomal-ionophores, however, showed antifungal activity along with low concentrations of Amphotericin B indicating the presence of synergism between these drugs.

Infect Immun, 1989 Jan, 57(1), 262 - 71
Identification of wall-specific antigens synthesized during germ tube formation by Candida albicans; Casanova M et al.; Walls of the two cellular forms (blastoconidia and mycelia) of Candida albicans ATCC 26555 were obtained from cells metabolically labeled (6-h pulse) with 14C-protein hydrolysate and {3H}threonine . Walls were purified by thorough washings with buffered and sodium dodecyl sulfate solutions and digested with Zymolyase 20T . The enzymatic treatment released four major high-molecular-weight mannoproteins (HMWM), with apparent molecular masses of 650, 500, 340, and 200 kilodaltons (HMWM-650, HMWM-500, HMWM-340, and HMWM-200, respectively), from yeast cells, whereas two high-molecular-mass mannoproteins (HMWM-260 and HMWM-180) were solubilized from mycelial cells . Some additional minor low-molecular-weight species were also detected in the enzymatic digests of walls from both types of cell . Single and dual pulse-chase experiments indicated that the HMWM-260 and HMWM-180 species reflect de novo synthesis of new proteins specific for the mycelia and do not represent a topological rearrangement of blastoconidium wall components . Monoclonal antibodies were raised against the HMWM-260 species (quantitatively the predominant component in the mycelial walls), and polyclonal rabbit antibodies were obtained against yeast or mycelial cell walls . Anti-mycelial cell wall polyclonal antibodies were adsorbed to whole killed blastoconidia to remove antibodies against common blastoconidium and mycelial wall antigens . Titration by enzyme-linked immunosorbent assay revealed that the monoclonal antibodies could recognize an epitope of the protein moiety of the HMWM-260 mannoprotein . Immunoblotting and immunofluorescence techniques using these monoclonal and polyclonal antibodies confirmed that the HMWM-260 and HMWM-180 species are specific components of the envelope of the mycelial cell walls.

Biochim Biophys Acta, 1988 Dec 9, 972(3), 277 - 82
Dimorphism-associated changes in intracellular pH of Candida albicans; Kaur S et al.; Intracellular pH (pHi) was monitored during pH-regulated dimorphism of Candida albicans using two different methods: (1) by steady-state distribution of propionic acid and (2) by use of polyene antibiotic, nystatin . There was no significant change in pHi during the first 120 min in either bud- or germ tube-forming populations . However, there was a rapid increase around 135 min which also coincided with the time of evagination . The magnitude of increase in pHi was different in the two populations; being 0.44 and 0.14 pH units in bud- and germ tube-forming populations, respectively . In the two diverging populations, the transient increase in pHi was followed by a rapid drop . The sharp rise in pHi of the population destined to form buds was sensitive to orthovanadate and to the depletion of K+ from the medium while this was not the case with germ tube-forming cells . The results suggest that pHi may play an important role in the phenotypic divergence of C . albicans.

J Pharm Sci, 1988 Dec, 77(12), 1050 - 4
5-( {aryl or aryloxy (or thio)}methyl)-3-(1H-imidazol-1-ylmethyl)-3- (2-thienyl)-2-methylisoxazolidine derivatives as novel antifungal agents; Mullen GB et al.; The in vitro antifungal activity of a novel series of cis- and trans-5-({aryl or aryloxy (or thio)}methyl)-3-(1H-imidazol-1-ylmethyl)-3- (2-thienyl)-2-methylisoxazolidines (13-24) was evaluated and compared with ketoconazole . The title series of compounds was prepared via a 1,3-dipolar cycloaddition reaction of 1-(2-thienyl)-2-(1H-imidazol-1-yl)-N-methylethanimine N-oxides with appropriate styrenes, allyl phenyl ethers, or allyl phenyl thioether precursors . The resulting products were mixtures of the corresponding cis- and trans-diastereomers which were readily separated by flash chromatography on neutral silica gel . The majority of compounds 13-24, when tested in solid agar cultures, exhibited moderate to potent activity against Trichophyton rubrum, Aspergillus fumigatus, and Candida albicans at concentrations ranging between less than or equal to 2.0 and 70.0 micrograms/mL.

Infect Immun, 1988 Dec, 56(12), 3162 - 6
Inoculation candidiasis in a murine model of severe combined immunodeficiency syndrome; Mahanty S et al.; To further elucidate the importance of T- and B-lymphocyte-mediated responses in host defense against systemic infection with Candida albicans, we studied this infection in a murine model of severe combined immunodeficiency (SCID) . The course of inoculation candidiasis in these mice, which lack functional T and B lymphocytes, was compared with that in immunologically normal BALB/c mice . Mice were inoculated intravenously with 10(5) yeast cells . Quantitative cultures of liver, spleen, and kidneys were performed with necropsy specimens obtained 1, 3, 7, 10, 14, and 21 days after this intravenous inoculation . The differences in the time courses of recovery of organisms from liver and spleen specimens were not significantly different in the SCID mice compared with the BALB/c mice . The recovery of C . albicans from the kidneys was significantly lower in the SCID mice, indicating less persistence of the organism in the kidneys of the SCID mice than in those of the BALB/c mice . These data indicate that defense mechanisms other than T- and B-lymphocyte-mediated mechanisms are primarily responsible for host defense against inoculation candidiasis.

J Neurooncol, 1988 Dec, 6(4), 329 - 38
Cell-mediated cytotoxicity in glioma-bearing patients: differential responses of peripheral blood mononuclear cells to stimulation with interleukin-2 and microbial antigen; Ausiello C et al.; Peripheral blood mononuclear cells (PBMC) of malignant glioma-bearing patients were stimulated in vitro with Interleukin-2 (IL-2) or a glucomannan-protein antigen of Candida albicans (GMP) then assayed for proliferation, production of IFN-gamma, and generation of cytotoxic effectors against either K562 tumor cell line or freshly-cultured allogenic glioma cells . PBMC of healthy, age and sex-matched subjects were the controls . PBMC of glioma-bearing patients did not differ, as a whole, from PBMC of healthy donors in IL-2 or GMP-induced proliferation . However, they showed a lesser ability to produce IFN as well as a substantial inability to generate cytotoxic effectors following GMP stimulation . PBMC of glioma patients were fully responsive to IL-2 in cytotoxicity generation, as were the PBMC from normal subjects . The results suggest that glioma patients may have a defective antigen-mediated activation of natural cytotoxic effectors . This hyporesponsiveness is not accompanied by depressed lymphoproliferation and does not apparently involve a reduced response to IL-2.

Eur J Clin Microbiol Infect Dis, 1988 Dec, 7(6), 736 - 41
Contribution of granulocytes and monocytes to resistance against experimental disseminated Candida albicans infection; van 't Wout JW et al.; The aim of the present study was to investigate the contribution of granulocytes and monocytes to resistance against an acute systemic candidal infection in mice . To this end granulocytopenia and monocytopenia were induced by irradiation or treatment with cyclophosphamide, and monocytopenia was obtained by treatment with VP-16 . After intravenous injection of 1 X 10(4) Candida albicans into mice irradiated with 8 GY, the number of Candida albicans cultured from the kidneys, expressed as the geometric mean of the number of CFU/g tissue, was 5.4 X 10(4), 7.1 X 10(6) and 5.8 X 10(7) on days 1, 3 and 5 of infection respectively (p less than 0.001 compared to normal mice) . The number of Candida albicans cultured from the liver and spleen was also significantly higher for irradiated animals than for normal mice (p less than 0.001) . For cyclophosphamide-treated mice the number of organisms in the kidney (1.7 X 10(4) CFU/g on day 1, 1.9 X 10(6) on day 3 and 3.8 X 10(6) on day 5 of infection) and spleen was significantly higher (p at least less than 0.02) than for normal mice after injection of 1 X 10(3) Candida albicans . Monocytopenia induced by VP-16 did not result in an increase in the number of Candida albicans cultured from the kidney or spleen after infection . From these studies it is concluded that granulocytes and not monocytes or exudate macrophages play an important role in resistance against Candida albicans during the first five days of a systemic infection.

Mycopathologia, 1988 Dec, 104(3), 129 - 35
Importance of some factors on the dimorphism of Candida albicans; Vidotto V et al.; The passage between the yeast and mycelial forms of Candida albicans B 311-10 was studied by using the minimal synthetic medium of Shepherd et al . modified without biotin and with low glucose concentrations . It was observed that biotin, aminoacids and particularly pH are not important factors in the dimorphism of C . albicans . The only factor of notable importance in the passage of yeast form to mycelial form in C . albicans was glucose concentration.

J Clin Microbiol, 1988 Dec, 26(12), 2626 - 31
In vitro susceptibilities and biotypes of Candida albicans isolates from the oral cavities of patients infected with human immunodeficiency virus; Korting HC et al.; Candida albicans strains were isolated from the oral cavities of 62 human immunodeficiency virus (HIV)-infected patients at different stages of HIV infection . Only patients with persistent generalized lymphadenopathy-acquired immunodeficiency syndrome (AIDS)-related complex or full-blown AIDS showed typical clinical symptoms for oral candidiasis . In general, the microbiological recovery of Candida strains from the oral cavity increased with more advanced stages of HIV infection . The antifungal activity of ketoconazole, itraconazole, nystatin, amphotericin B, and flucytosine against all 62 strains was evaluated by means of a photometer-read broth microdilution method for determination of the 30% inhibitory concentrations of the drugs . The 95% ranges of 30% inhibitory concentrations were as follows: less than or equal to 0.063 to 32 micrograms/ml for ketoconazole, less than or equal to 0.063 to 8 micrograms/ml for itraconazole, 0.5 to 4 micrograms/ml for nystatin, less than or equal to 0.063 to 4 micrograms/ml for amphotericin B, and less than or equal to 0.063 to 8 micrograms/ml for flucytosine . Two strains were resistant to flucytosine, one was resistant to ketoconazole, and three were resistant to itraconazole . Isolates from patients with full-blown AIDS showed significantly less susceptibility to itraconazole, amphotericin B, and flucytosine . Strains were biotyped by using the API 20C carbohydrate assimilation system . The major biotype accounted for 63.9% of the isolates . At repeated evaluation, a change in biotype pattern was seen in 27.3%.

Oral Surg Oral Med Oral Pathol, 1988 Dec, 66(6), 670 - 3
Adherence in vitro of various Candida species to acrylic surfaces; Segal E et al.; Adherence of microorganisms to the surfaces of the host is believed to be an initial and essential step in the production of infection . The objective of the present study was to compare the adherence in vitro of 17 isolates of various Candida species to acrylic surfaces . The results showed that all 17 Candida strains adhered to acryl . Generally, all Candida albicans strains were more adherent than the other strains of Candida species that were tested . Marked differences in the adherence ability of strains belonging to the same species were noted . Future studies to search for possible association between adherence of Candida strains to acryl and pathogenesis of denture stomatitis are planned.

J Med Microbiol, 1988 Dec, 27(4), 239 - 45
Electric and chemical fusions for the production of monoclonal antibodies reacting with the in-vivo growth phase of Candida albicans; Fortier B et al.; To obtain monoclonal antibodies (MAbs) directed preferentially against the pathogenic phase of Candida albicans, mice were immunised with germ tubes of C . albicans serotype A, strain VW.32, killed by exposure to ultraviolet (UV) irradiation . Fusions were performed either by the standard chemical procedure with polyethylene glycol, or by electric discharge following linkage of the myeloma and lymphocyte cells with a Concanavalin A-mannoprotein bridge . The preliminary characteristics of one MAb obtained from each of these fusions are described . An IgM antibody (3B7) obtained from the chemical fusion reacted with a polysaccharide antigen that was heterogeneously distributed on both in-vitro and in-vivo forms of C . albicans . This MAb agglutinated different strains of C . albicans irrespective of their serotype . An IgG1 antibody (3G6) that had been obtained from the electric fusion was found to react in vitro with a proteinaceous antigen located only on the germ tubes of strain VW.32 . However, MAb 3G6 displayed strong reactivity against all growth forms of C . albicans in vivo and reactivity extended to other strains.

J Med Microbiol, 1988 Dec, 27(4), 227 - 32
Characterisation and cellular localisation of the immunodominant 47-Kda antigen of Candida albicans; Matthews R et al.; The 47-Kda component of Candida albicans is an immunodominant antigen in the serology of systemic candidosis . Immuno-electronmicroscopy with an affinity-purified antibody to the 47-Kda antigen showed that it was present in the cytoplasm and cell wall of both yeast and mycelial cells . It was found in discrete areas on the inner and outer borders of the cell wall and was mainly located within the wall rather than exposed on the outer surface . Sometimes it appeared to be in channels across the cell wall . In the cytoplasm, it was usually near the cytoplasmic membrane and occasionally appeared in vesicular areas . It was not detected in the nucleus or mitochondria . The 47-Kda antigen did not bind to Concanavalin A, and antigenicity was lost after protease digestion . Peptide mapping suggested that the antigen was highly conserved between different strains of C . albicans.

J Infect Dis, 1988 Dec, 158(6), 1268 - 76
Impaired neutrophil function in patients with AIDS or AIDS-related complex: a comprehensive evaluation; Ellis M et al.; We measured the neutrophil function of 6 patients with AIDS and Kaposi's sarcoma (KS); 22 patients with AIDS-related complex (ARC); and 28 healthy, heterosexual controls . Neutrophils from patients with ARC showed significantly less chemotaxis (P less than or equal to .025) than did those from patients with AIDS and KS or from controls . Serum from patients with AIDS and KS or with ARC significantly (P less than or equal to .05) inhibited chemotaxis of neutrophils from controls; heat treatment of the serum abolished this inhibitory effect . Bacterial killing by neutrophils from patients with AIDS and KS or with ARC was also significantly (P less than or equal to .05) less than for neutrophils from controls, as was neutrophil phagocytosis binding of Candida albicans (P less than or equal to .05) . Expression of OKM1 antigen was increased in the patients studied . Enzyme degranulation, adherence, and aggregation were also examined . The defects found in neutrophil function are selective and may be important in the increased susceptibility of patients with human immunodeficiency virus infection to bacterial and fungal infections.

Clin Chem, 1988 Dec, 34(12), 2423 - 5
Quantitative precipitin reaction and enzyme-linked immunosorbent assay of mannans of Candida albicans NIH A-207 and NIH B-792 strains compared; Tojo M et al.; We assessed the difference between results by enzyme-linked immunosorbent assay (EIA) in plastic support wells and the quantitative precipitin reaction (QPR) in glass test tubes for antigenic mannans and antibodies of two representative Candida albicans strains, NIH A-207 and NIH B-792 . We investigated each of four mannan subfractions, with different phosphate contents, for their reactivities to the homologous polyclonal rabbit antiserum . Each series of mannan subfractions showed a reactivity proportional to their phosphate content in EIA, in a similar manner as observed in QPR . Moreover, in EIA, the cross-reactivities between the bulk mannans of the two C . albicans strains and the polyclonal antiserum of a Saccharomyces cerevisiae wild-type strain containing specific antibodies to the non-reducing terminal alpha-1,3-linked D-mannopyranose unit resembled those of the same antigen-antibody reactions in QPR . However, the mannan of C . albicans NIH A-207 strains, a weak antigen in the cross-QPR system, reacted fairly strongly in EIA in its high concentration range, indicating that EIA can be used to detect such an epitope in these mannans in concentrations undetectable by QPR . We conclude that EIA is a useful technique for immunochemical assay of yeast mannans and their antibodies on a smaller scale than with QPR.

J Immunol, 1988 Dec 1, 141(11), 4047 - 52
Tumor necrosis factor induction by Candida albicans from human natural killer cells and monocytes; Djeu JY et al.; Other investigators have previously reported that TNF has been induced from macrophages by bacteria and, more recently, from NK cells by certain tumor cells . Sendai virus has also been reported to induce TNF from macrophages . We report here that an opportunistic fungi, Candida albicans, can also induce TNF, not only from human monocytes, but also from Percoll-fractionated large granular lymphocytes (LGL) which mediate NK function . Incubation of monocytes of LGL with C . albicans for 8 h was sufficient for detection of TNF release and peak induction was observed at 24 h . Induction of TNF from LGL did not require the participation of monocytes or T cells because treatment of the LGL with CD14 or CD15 to eliminate contaminating monocytes and CD3, CD4, or CD8 to eliminate contaminating T cells did not decrease the level of TNF produced from the treated LGL . Small T cells recovered from the denser fractions of the Percoll gradient had no ability to produce TNF, even when 10% monocytes were added to the T cells to provide accessory function . The phenotype of the TNF-producing LGL was CD2+, CD11+, CD16+, NKH1+, LEU7- . The TNF produced by both monocytes and LGL was neutralized by specific monoclonal and polyclonal anti-TNF but not by monoclonal antilymphotoxin . These results indicate that TNF production is a normal response of monocytes and LGL to stimulation by fungi such as C . albicans and that the release of TNF may be related to its ability to activate effector function to control Candida growth, which we have shown earlier for neutrophils with TNF.

Antimicrob Agents Chemother, 1988 Dec, 32(12), 1901 - 3
Cilofungin (LY121019) inhibits Candida albicans (1-3)-beta-D-glucan synthase activity; Taft CS et al.; Cilofungin (LY121019) inhibited Candida albicans growth and activity of (1-3)-beta-glucan synthase, for which it was a noncompetitive inhibitor with a Ki-app of 2.5 microM . Cilofungin had no effect on chitin synthase activity . Based on these and other data, it seems likely that cilofungin inhibits fungal growth by inhibiting (1-3)-beta-glucan synthase activity.

Scand J Gastroenterol, 1988 Dec, 23(10), 1182 - 6
Esophageal candidosis in progressive systemic sclerosis: occurrence, significance, and treatment with fluconazole; Hendel L et al.; Esophageal mucosal brushings from 51 consecutive patients with progressive systemic sclerosis (PSS) (group I), 18 PSS patients continuously treated with high-dose ranitidine or omeprazole (group II), 34 controls referred to the outpatient clinic for endoscopy (group III), and 10 patients receiving long-term potent antireflux therapy for idiopathic gastroesophageal reflux (group IV) were cultured for Candida albicans . There were 44%, 89%, 9%, and 0% Candida albicans culture-positive patients in groups I through IV, respectively . Fifteen patients with candida esophagitis from group II were treated with fluconazole systemically . Eleven and 14 patients became culture-negative after 2 and 4 weeks' treatment, respectively . Three months after fluconazole withdrawal the recurrence rate was 100% . It is concluded that esophageal dysmotility predisposes for candidosis . Adding gastric acid inhibitory treatment to dysmotility enhances the risk significantly (p less than 0.01) . The efficiency of fluconazole treatment was close to 100%, but so was the recurrence rate within a short period.

J Med Microbiol, 1988 Dec, 27(4), 233 - 8
Production and characterisation of a monoclonal antibody to a cell-surface, glucomannoprotein constituent of Candida albicans and other pathogenic Candida species; Cassone A et al.; A murine monoclonal antibody (MAB AF-1) class IgM was raised to a soluble glucomannoprotein extract (GMP) of Candida albicans . Agglutination and indirect immunofluorescence assays with purified MAB showed that AF-1 was directed against a cell-surface epitope shared by C . albicans serotypes A and B, C . tropicalis, C . guilliermondii and C . viswanathii, but not by C . krusei, C . parapsilosis, C . kefyr (pseudotropicalis) and T . glabrata . Treatment with heat, protease or periodate-treated GMP and with other cell-wall extracts of C . albicans provided evidence that the epitope recognised by MAB AF-1 is carried by the polysaccharide moiety of cell-surface glucomannoprotein molecule(s).

Infect Immun, 1988 Dec, 56(12), 3294 - 6
Interactions of monospecific antisera with cell surface determinants of Candida albicans; Chaffin WL et al.; Flow cytometric analysis of indirect immunofluorescence showed that surface determinants recognized by antisera (Candida Check; Iatron Laboratories, Tokyo, Japan) for factors 1, 4, 5, and 6 were expressed to the same extent by all cells of Candida albicans under each growth condition and for each morphology examined . Fluorescence intensity increased with increasing cell size.

Lancet, 1988 Nov 19, 2(8621), 1163 - 5
Neutrophil death as a defence mechanism against Candida albicans infections; McNamara MP et al.; In studies of experimental Candida albicans infections, growth of invading organisms sometimes ceased before the organisms reached the neutrophil infiltrates . Lysates of human neutrophils inhibited the directed growth of candida pseudohyphae in agarose gel and suppressed the proliferation of candida yeast in broth cultures, but did not kill the organisms or prevent their germination . The growth-inhibitory material released from disrupted neutrophils had an estimated molecular weight of 30 kD and differed from most previously described neutrophil antimicrobial factors in that it was present in cell sap rather than granules, and did not appear in the supernatant after stimulation of the cells . Neutrophil death and dissolution may represent an alternative host defence mechanism against invasive C albicans infection.

J Infect Dis, 1988 Nov, 158(5), 1065 - 70
An emulsion formulation of amphotericin B improves the therapeutic index when treating systemic murine candidiasis; Kirsh R et al.; Incorporating amphotericin B into liposomes was reported to decrease amphotericin B toxicity without a concomitant loss of antifungal efficacy . We formulated an alternative emulsion-based delivery system for amphotericin B and compared it with Fungizone . The maximal tolerated dose (MTD) in mice was 1 mg of Fungizone/kg; however, the MTD was greater than 9 mg of the Intralipid emulsion formulation/kg . The emulsion formulation and Fungizone were equipotent for treating systemic candidiasis in mice . Amphotericin B nephrotoxicity, as manifested by polyuria that was resistant to antidiuretic hormone, was markedly diminished when amphotericin B was administered as an emulsion to rats . Loss of potassium from human red blood cells was also reduced by formulating this agent within emulsions . The emulsion formulation extended the survival time of mice that had established Candida albicans infections, when compared with the Fungizone treatment . The efficacy and reduced toxicity of the amphotericin B emulsion are findings suggesting that the emulsion formulation is preferable to Fungizone.

Dev Biol, 1988 Nov, 130(1), 198 - 208
High-frequency switching in Dictyostelium; Kraft B et al.; A high-frequency switching system is demonstrated to exist in Dictyostelium discoideum . Switch phenotypes are distinguished by colony morphology and include changes in developmental timing as well as blocks in morphogenesis . The switching system exhibits the following characteristics: (1) a "low" spontaneous frequency of switching (approximately 10(-2} in the parent strain; (2) stimulation of the basal level of switching roughly fivefold with low doses of ultraviolet light; (3) "high" spontaneous frequencies of switching (as high as 10(-1} in particular variant strains; (4) high spontaneous frequencies of interconvertibility between variant phenotypes; (5) high spontaneous frequencies of reversion to the wild-type phenotype; (6) a set of reproducible switch phenotypes; (7) heritability of switch phenotypes; and (8) a rough correlation between switch phenotype and switching frequency . The extraordinary similarity between the switching systems in D . discoideum and Candida albicans is discussed.

J Leukoc Biol, 1988 Nov, 44(5), 422 - 33
Nonspecific and Candida-specific immune responses in mice suppressed by chronic administration of anti-mu; Kuruganti U et al.; CBA/J mice were immunosuppressed by repeated administration of goat antibody specific for mu chain of immunoglobulin M (IgM) and tested for nonspecific and Candida albicans-specific immune responses . Immunosuppression was demonstrated by a dramatic reduction in the number of antibody-forming cells in the spleens of anti-mu-treated mice when immunized with sheep erythrocytes, by greatly reduced in vitro responsiveness of both spleen and lymph node lymphocytes from anti-mu-treated mice to lipopolysaccharide, and by a large reduction in the number of splenic IgM-positive cells . T cell function, on the other hand, appeared to be relatively unaltered in anti-mu-treated animals, in the cytotoxic T lymphocyte activity against an allogeneic target was similar in splenocyte cultures from anti-mu- and mock-treated animals, and splenic and lymph node lymphocytes proliferated in response to concanavalin A in a lymphocyte stimulation assay . Moreover, Candida-specific delayed hypersensitivity to two different Candida antigens, one cell wall-derived (GP) and the other cell membrane-derived (BEX), was of comparable intensity in immunosuppressed and normal animals . When anti-mu- and mock-treated mice were immunized by the cutaneous inoculation of viable C . albicans blastospores and then challenged intravenously to assess the development of protective immunity, only mock-treated animals, male and female, had significant (p less than or equal to 0.05) protective responses demonstrable by reduction in the number of colony-forming units cultured from their kidneys 28 days after intravenous challenge . If consideration was given to the number of animals which had cleared Candida completely from the kidney, however, there appeared to be protective responses operative in the female anti-mu-treated animals as well . Neither anti-mu-treated males nor females, when immunized and challenged with C . albicans, produced Candida-specific antibody detectable by counterimmunoelectrophoresis, whereas all immunized and challenged mock-treated animals produced antibody . The data are consistent with the hypothesis that anti-mu treatment has little effect on multiple cellular immune functions, including those specific for C . albicans, and the combination of antibody, cell-mediated immunity and innate defenses are responsible for solid systemic defense against the fungus.

J Gen Microbiol, 1988 Nov, 134 ( Pt 11), 2917 - 24
Studies on the anticandidal mode of action of Allium sativum (garlic); Ghannoum MA; The mode of action of aqueous garlic extract (AGE) was studied in Candida albicans . The minimum inhibitory concentration (MIC) of AGE against six clinical yeast isolates ranged between 0.8 and 1.6 mg ml-1 . Scanning electron microscopy and cell leakage studies showed that garlic treatment affected the structure and integrity of the outer surface of the yeast cells . Growth of C . albicans in the presence of AGE affected the yeast lipid in a number of ways: the total lipid content was decreased; garlic-grown yeasts had a higher level of phosphatidylserines and a lower level of phosphatidylcholines; in addition to free sterols and sterol esters, C . albicans accumulated esterified steryl glycosides; the concentration of palmitic acid (16:0) and oleic acid (18:1) increased and that of linoleic acid (18:2) and linolenic acid (18:3) decreased . Oxygen consumption of AGE-treated C . albicans was also reduced . The anticandidal activity of AGE was antagonized by thiols such as L-cysteine, glutathione and 2-mercaptoethanol . Interaction studies between AGE and thiols included growth antagonism, enzymic inhibition and interference of two linear zones of inhibition . All three approaches suggest that AGE exerts its effect by the oxidation of thiol groups present in the essential proteins, causing inactivation of enzymes and subsequent microbial growth inhibition.

Immunopharmacology, 1988 Nov-Dec, 16(3), 151 - 5
Effect of ketorolac on phagocytosis of Candida albicans by peritoneal macrophages; Fraser-Smith EB et al.; The effect of ketorolac tromethamine, a nonsteroidal anti-inflammatory drug, on normal phagocytosis has been studied . When peritoneal macrophages, taken from mice treated intraperitoneally 4 times daily for 7 days with 2 mg ketorolac per day, were cultured ex vivo or when untreated macrophages were cultured with 1-10 microM of ketorolac in vitro, the number of engulfed Candida albicans was no different from saline-treated or untreated controls . In contrast, macrophages from mice treated intraperitoneally 4 times daily for 7 days with 0.4 mg dexamethasone per day or cultured with 1-10 microM dexamethasone had a greater than or equal to 54% reduction in phagocytosis (p less than 0.001) . Thus, ketorolac is a nonsteroidal anti-inflammatory drug which does not inhibit the phagocytic activity of murine mononuclear phagocytes.

Mycopathologia, 1988 Nov, 104(2), 81 - 5
The effect of monosaccharides on in situ hepatic trapping of Candida albicans; Sawyer RT; The initial clearance of Candida albicans in situ by hepatic tissue was investigated using the isolated perfused mouse liver model in combination with various monosaccharides . When 10(6) yeasts were infused into untreated ICR mouse livers, approximately 61 +/- 2% (mean + SEM) were recovered from the liver and 13 +/- 2% in the effluent for a total recovery of 74 +/- 2% . This suggests that 26 +/- 2% of the infused yeasts were eliminated within the liver and that a total of 87 +/- 1% were trapped (% in the liver + % killed) by the liver . In contrast, when either D-mannose or alpha-methyl-D-mannoside, but not glucose, sucrose, lactose or mannitol, were added to perfusion media (1% w/v) the ability of hepatic tissue to trap C . albicans decreased, in a dose-dependent manner, with increasing concentrations of monosaccharide . Decreased trapping was due to the interaction of these monosaccharides with hepatic tissue and not directly with yeasts . The data suggest that one component of in situ hepatic clearance of C . albicans was the binding of mannose containing structures on the surface of yeasts, most probably by hepatic mannose receptors.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1988 Nov, 269(3), 377 - 86
Synergism of Candida albicans and delta toxin producing Staphylococcus aureus on mouse mortality and morbidity: protection by indomethacin; Carlson EC; Twelve Staphylococcus aureus strains, six positive and six negative for delta-toxin production, were studied for synergistic effects on mouse mortality and morbidity when combined with Candida albicans and inoculated intraperitoneally (i.p.) . S . aureus strains producing delta-toxin were found to exhibit a relatively great synergistic decrease (between near 10(3)-10(5)-fold) in LD50 (dose necessary to kill 50% of exposed animals in five days) when combined with a nonlethal dose of C . albicans and injected i.p . S . aureus strains which did not produce delta showed less of a synergistic effect with C . albicans (10-10(2)-fold drop in LD50) . A synergistic effect on mortality could also be produced when animals were dually injected with C . albicans and sterile growth filtrates from the delta-toxin producing strains or the purified delta-toxin . The lethal agent in the culture filtrate was, like delta-toxin, sensitive to lecithin and insensitive to heat . Indomethacin protected animals from the C . albicans-filtrate induced death . Blood measurements made following i.p . injection of delta-toxin and C . albicans revealed chemistry changes indicative of shock, kidney and liver damage; delta-toxin alone caused no significant chemistry changes whereas C . albicans alone caused some blood chemistry changes but liver and kidney damage was not indicated . No synergism on mortality was found between C . albicans and purified alpha-toxin or toxic shock syndrome toxin-1.

Mol Cell Biol, 1988 Nov, 8(11), 4721 - 6
Assignment of cloned genes to the seven electrophoretically separated Candida albicans chromosomes; Magee BB et al.; By using orthogonal-field alternating gel electrophoresis (OFAGE), field-inversion gel electrophoresis (FIGE), and contour-clamped homogeneous field gel electrophoresis (CHEF), we have clearly resolved 11 chromosomal bands from various Candida albicans strains . OFAGE resolves the smaller chromosomes better, while FIGE, which under our conditions causes the chromosomes to run in the reverse order of OFAGE, is more effective in separating the larger chromosomes . CHEF separates all chromosomes under some conditions, but these conditions do not often resolve homologs . The strains examined are highly polymorphic for chromosome size . Fourteen cloned Candida genes, isolated on the basis of conferral of new properties to or complementation of auxotrophic deficiencies in Saccharomyces cerevisiae, and three sequences of unknown function have been hybridized to Southern transfers of CHEF, FIGE, and OFAGE gels . Four sets of resolvable bands have been shown to be homologous chromosomes . On the basis of these data, we suggest that C . albicans has seven chromosomes . Genes have been assigned to the seven chromosomes . Two chromosomes identified genetically have been located on the electrophoretic karyotype.

Infect Immun, 1988 Nov, 56(11), 2884 - 90
Role of yeast cell growth temperature on Candida albicans virulence in mice; Antley PP et al.; Previous studies have suggested that yeast cell growth temperature may influence the relative virulence of the opportunistic dimorphic fungus Candida albicans . To test this possibility, mice were challenged with C . albicans yeast cells which were grown at either room temperature or 37 degrees C, and their survival was monitored daily . Mice which received room temperature-grown cells died faster . The interaction of glycogen-elicited polymorphonucleated neutrophils (PMNs) with C . albicans yeast cells grown at the two temperatures was examined, because PMNs have been shown to have a critical role in preventing development of candidiasis in normal individuals . In the absence of serum (i.e., nonopsonic conditions), more PMNs conjugated and engulfed C . albicans cells grown at room temperature than those grown at 37 degrees C . However, PMNs were less able to kill cells grown at room temperature than cells grown at 37 degrees C . Cells grown at room temperature also produced abundant germ tubes after engulfment and were thus more likely to escape killing by phagocytes . These results suggest that cells grown at room temperature are more virulent because they are less likely to be killed by phagocytes and are more likely to disseminate . The possibility that expression of cell surface hydrophobicity is involved in these events is discussed.

Przegl Dermatol, 1988 Nov-Dec, 75(6), 425 - 30
{New possibilities of prevention of occupational Candida albicans infection}; Maleszka R et al.; The effects were studied in vitro of a score of various additives to toilet soaps on strains of Candida albicans isolated from patients . Their effect on the basic properties of toilet soaps was studied, determining foam production and the index of foam stability, and their resistance to high temperature was determined since in the process of production high temperature might reduce their effects on C . albicans . The strongest fungicidal effect was exerted in strongly alkaline soap solutions by Clotrimazole . Good effects were obtained also using Clioquinol, a derivative of 8-hydroxyquinoline . The results of these studies suggest that certain substances may be added for exerting a fungicidal effect in alkaline medium protecting thus against fungal infections.

Immunology, 1988 Nov, 65(3), 405 - 9
Macrophage function in chronic experimental alcoholism . I . Modulation of surface receptors and phagocytosis; Bagasra O et al.; In the present study, we have assessed peritoneal, alveolar and splenic macrophages for expression of Fc and C3b surface receptors and their ability to function in immunophagocytosis . We have also measured their oxidative burst response by the nitroblue tetrazolium dye (NBT) reduction method . Our studies revealed that macrophages harvested from chronic alcoholic rats expressed surface C3b and Fc receptors, with significantly higher surface density than macrophages of litter-mate controls (matched for sex and nutritional calories) . However, the ability of macrophages from alcoholic rats to phagocytize through C3b and Fc receptors was significantly impaired . In addition, the ability of peritoneal macrophages from alcoholic animals to ingest non-opsonized Candida albicans and to reduce NBT dye was markedly compromised . Abnormalities of macrophage function may, at least in part, account for an increased susceptibility of alcoholic patients to infection.

Can J Microbiol, 1988 Nov, 34(11), 1183 - 8
The requirements for bicarbonate and metabolism of the inducer during germ tube formation by Candida albicans; Pollack JH et al.; Factors affecting germ tube formation in Candida albicans at suboptimal temperatures were investigated . Candida albicans formed germ tubes between 22 and 30 degrees C in solution when incubated without shaking, in the presence of bicarbonate (2 mg mL-1) . Other conditions depended on the inducer used . Proline could induce germ tube formation optimally only when its concentration was between 200 and 400 mM . A concentration of 0.05 mM N-acetylglucosamine was sufficient to induce germ tube formation . N-Acetylglucosamine could induce germ tube formation at 30 but not at 25 degrees C . N-Acetylglucosamine induced germ tube formation was most reproducible when the cells were first starved by incubation in water for 16-24 h at 20 degrees C . Germ tubes induced by proline could be formed at pH values between 3.8 and 9.0 at 30 degrees C, but only between 7.0 and 7.5 at 25 degrees C . The addition of 0.05 to 5 mM glucose to a 5 mM proline induction solution allowed germ tube formation at 30 but not at 25 degrees C . Glucose (400 mM) did not suppress germ tube formation at 30 degrees C but only 5 mM was sufficient to cause a 65% suppression at 25 degrees C . The results show the importance of CO2 and (or) bicarbonate to the induction of germ tube formation and are consistent with the metabolism of the inducer.

J Infect Dis, 1988 Nov, 158(5), 1056 - 64
Induction of signal transduction in human neutrophils by Candida albicans hyphae: the role of pertussis toxin-sensitive guanosine triphosphate-binding proteins; Lyman CA et al.; Nonopsonized Candida hyphae elicit from human neutrophils a transient rise in cytosolic calcium concentrations and an oxidative burst without a detectable change in membrane potential . To determine if the signal-transduction pathway used by these organisms is mediated by guanine nucleotide-binding proteins (GNPs), we examined the functional responsiveness of neutrophils pretreated with pertussis toxin (PT) . In response to serum-opsonized hyphae or zymosan, the rise in cytosolic calcium, membrane depolarization, and the respiratory burst were only partially abrogated . The transient rise in calcium induced by unopsonized hyphae was, however, completely eliminated in PT-treated neutrophils . Despite total abrogation of the calcium response, PT-treated cells could still mount a respiratory burst in response to these nonopsonized hyphae . Thus, neutrophil signaling by both serum-opsonized particles and nonopsonized hyphae is only partially mediated by PT-sensitive GNPs . Furthermore, the ability of unopsonized hyphae to elicit a respiratory burst without a calcium response suggests these events are separable and confirms the versatility of these organisms as probes for investigating neutrophil activation.

Mycopathologia, 1988 Oct, 104(1), 47 - 50
Fungal infections of ear with special reference to chronic suppurative otitis media; Talwar P et al.; Fungus were found to take important role in ear infections of the 344 patients (CSOM 286, Otomycosis 44, Otitis externa 14), significant fungal infections (with positive smear and culture) were detected on 49%, 79.5%, 66.6% patients respectively . 84.8% patients were detected both by smear and culture, 14.1% patients by culture and 0.1% patients in smear preparation only . In CSOM patients, age predominated in 20-27 yrs group, sex in male below 30 yrs, and Aspergillus flavus, A . niger, Penicillium, A . fumigatus in mycelial fungus, Candida albicans, C . parapsillosis in yeast . But in 18 post antibiotic fungus infected patients Penicillium and A . niger were the important isolates . In otomycosis and otitis externa patients A . niger took the main role.

J Med Chem, 1988 Oct, 31(10), 2008 - 14
Studies on antifungal agents . 23 . Novel substituted 3,5-diphenyl-3-(1H-imidazol-1-ylmethyl)- 2-alkylisoxazolidine derivatives; Mullen GB et al.; The synthesis and antifungal activity of a novel series of substituted 3,5-diphenyl-3-(1H-imidazol-1-ylmethyl)-2-alkylisoxazolidine derivatives (15-30) are described . The synthesis of the title compounds was accomplished via a 1,3-dipolar cycloaddition reaction of alpha-substituted ketonitrones with appropriate styrene precursors . The compounds when tested in vitro in solid agar cultures exerted a very potent antifungal activity against a wide variety of yeast and systemic mycoses and dermatophytes, especially Trichophyton and Microsporum sp., Epidermophyton floccosum and Candida stellatoidea . The in vitro activity against Aspergillus fumigatus and Candida albicans was moderate to potent . Overall, the two bis(4-chlorophenyl) analogues 18 and 19 were the most potent in vitro compounds, showing MIC values ranging between 0.2 and 7.0 microgram/mL, as compared to 0.2-20.0 micrograms/mL for ketoconazole, which was used as the positive standard in all assays . When tested in vivo in the rat vaginal candidiasis model, derivative 18, although showing significant antifungal activity when compared to controls, was less effective than ketoconazole . The title 3,5-substituted isoxazolidine compounds represent a novel class of potent antifungal agents.

Microbiologica, 1988 Oct, 11(4), 307 - 19
A further insight into the mechanism of action of anthracycline antibiotics; Palu G et al.; The uptake of Adriamycin (ADM) by eucaryotic and procaryotic cells and the interaction of the antibiotic with structurally organized DNA were investigated . The aim of this work was to understand why ADM is endowed with very low antibiotic activity in spite of being highly cytotoxic for mammalian cells, and to get a further insight into the mechanism of action of this compound . Spectrophotometric, fluorometric, chiroptical, and electron microscopic techniques were used . The drug was shown to concentrate in mammalian cells but failed to do so in bacteria and penetrated rather poorly in Candida albicans . The chromatin binding affinity of ADM appeared to be substantially reduced with respect to the affinity for free DNA . Complex stereochemistry was also influenced by the presence of nucleosomal arrangements in the polynucleotide . In addition, evidence was obtained that the antibiotic tended to accumulate at specific (linker) chromatin regions and to cause extensive compaction of organized DNA . The observed phenomena may play a relevant role in the mode of drug action in eucaryotic cells and help to explain the lack of antibacterial activity by ADM in spite of the apparent attainment of great enough intracellular levels to affect DNA template function.

J Cell Sci, 1988 Oct, 91 ( Pt 2), 211 - 20
Variation in cytoplasmic microtubule organization and spindle length between the two forms of the dimorphic fungus Candida albicans; Barton R et al.; Candida albicans is a dimorphic fungus capable of growing as a budding yeast and as a filamentous hypha . We have used the technique of immunofluorescence to study the changes in the microtubule cytoskeleton during the cell cycle in both growth forms . This approach has revealed the presence of an extensive system of microtubules, including cytoplasmic microtubules and a rod-like intranuclear spindle . We have provided a complete description of the arrangement of cytoplasmic and spindle microtubules at each phase of the yeast cell cycle . A novel and characteristic feature of the yeast phase of Candida is the presence of an array of short microtubules at the neck of the doublet cell . This neck-associated array (NAA), is apparently organized independently of the main microtubule-organizing centre, the spindle pole bodies, at late anaphase . Analysis of microtubule patterns in the hyphal state reveals that the general arrangements of microtubules are similar to those seen in the yeast phase . These patterns suggest a role for the cytoplasmic microtubules in the nuclear migration that occurs during hyphal growth . A major finding is that the mitotic spindle in hyphae is considerably longer (12-20 microns) than the spindle in yeast cells (7-8 microns) . This may reflect the role of the hyphal mitotic spindle not only in nuclear division but also in the positioning of the daughter nuclei at the centres of hyphal compartments.

J Gen Microbiol, 1988 Oct, 134 ( Pt 10), 2841 - 7
Pyrolysis mass spectrometry as a method for inter-strain discrimination of Candida albicans; Magee JT et al.; A claim that Candida albicans strains NCPF 3153 and B311 were identical was investigated . Authentic strains were shown to be distinct (P less than 0.1%) by pyrolysis mass spectrometry (PyMS) . Of twelve strains, provided as clones of NCPF 3153, seven were authenticated, one yielded an equivocal result and four were distinct from both NCPF 3153 and B311 . Of eight B311 clones, six were authenticated and two yielded equivocal results . Although five non-C . albicans yeast strains were identified as distinct from B311 and NCPF 3153, Torulopsis glabrata NCPF 3240 was identified as B311, and one clinical isolate of C . albicans as NCPF 3153 . This could be explained by the specificity of the mathematical analysis for discrimination between the authentic strains.

J Gen Microbiol, 1988 Oct, 134 ( Pt 10), 2693 - 702
Binding of plasma proteins to Candida species in vitro; Page S et al.; The ability of purified human albumin, fibrinogen and transferrin to bind to Candida species was measured by immunofluorescence . The proteins all bound with high avidity to germ-tubes formed by Candida albicans, but did not bind to blastospores of C . albicans or other pathogenic Candida species, not even to parent blastospores bearing germ-tubes . The extent of binding of the proteins to C . albicans germ-tubes varied between growth media and from germ-tube to germ-tube . Strains of C . albicans that did not form germ-tubes were incapable of binding any of the proteins . There was evidence that purified fibrinogen bound to germ-tubes with higher avidity than albumin and transferrin . When germ-tubes were treated with whole human plasma or serum, indirect immunofluorescence revealed that proteins were bound all over the surface of C . albicans blastospore-germ-tube units, indicating behaviour different from that seen with the purified proteins tested alone or in mixtures . C . albicans cells grown in the presence of azole antifungal agents bound purified plasma proteins in the same way as cells untreated with the drugs . The results of this study suggest that binding of host proteins to the surface of C . albicans may not be a property related directly to virulence of the fungus in vivo.

Ophthalmology, 1988 Oct, 95(10), 1450 - 7
Late bacterial and fungal keratitis after corneal transplantation . Spectrum of pathogens, graft survival, and visual prognosis; Harris DJ Jr et al.; The authors reviewed 108 bacterial and fungal corneal ulcers that developed 1 to 72 months after penetrating keratoplasty in 79 eyes of 78 patients . Graft hypesthesia, topical corticosteroid and antibiotic treatment, exposed sutures, epithelial defects, and poor visual acuity commonly predated infectious keratitis . There were 69 bacterial, 34 fungal, and 5 combined infections . Candida albicans and Staphylococcus epidermidis were the most common pathogens . Follow-up after infection averaged 23 months (range, 1-80 months) . Despite hospitalization and fortified topical antibiotic treatment, complications such as wound dehiscence and corneal perforation necessitated emergency regraft in 38 (35%) cases . Of 73 previously clear grafts, only 29 (40%) retained clarity . Median visual acuity, 20/200 before infection, fell to counting fingers at last follow-up; 12 eyes lost light perception.

Mycopathologia, 1988 Oct, 104(1), 7 - 17
Studies on detection of Candida antigen in the sera of mice inoculated orally with Candida albicans; Suzuki H et al.; The authors succeeded in establishing a murine model of systemic candidiasis being disseminated from the primary gastrointestinal lesions caused by oral inoculation of Candida albicans . Using this model, an attempt was made for detecting the Candida antigen by enzyme-linked immunosorbent assay using avidin-biotin (AB-ELISA) from the serum of infected mice . Gastrointestinal candidiasis was formed in all of the 20 mice treated with the drugs (antibiotics, antineoplastic agents, hydrocortisone, etc.) and inoculated orally with C . albicans . Fourteen of these mice suffered from submucosal candidiasis, and C . albicans was cultured from the visceral organs in 12 of them . The assay by AB-ELISA was able to detect 1.0 ng/ml Candida mannan in the mouse serum . The Candida antigen was detected in the sera of 11 of the 14 mice with submucosal candidiasis . However, the antigen could not be detected in the sera of the 6 mice with intramucosal candidiasis . The assay by AB-ELISA is more sensitive and specific for the diagnosis of systemic candidiasis than other serological assays.

Acta Odontol Scand, 1988 Oct, 46(5), 267 - 72
Treatment of angular cheilitis . The significance of microbial analysis, antimicrobial treatment, and interfering factors; Ohman SC et al.; This prospective study evaluated the significance of microbial analysis and antimicrobial treatment for the cure of angular cheilitis . Furthermore, various etiologic factors were investigated for their relative effect on the healing process . The study included 1) an open trial with 50 patients infected by Candida albicans and/or Staphylococcus aureus, and 2) an intraindividual comparison of eight patients with bilateral lesions infected by Candida albicans as the only detected pathogen . After a base-line examination the patients received ointments containing nystatin and/or fusidic acid, on the basis of the outcome of an initial microbial analysis . The patients were evaluated clinically, photographed, and examined for microorganisms at different time intervals . Ninety-six per cent of the patients who participated in the open trial had no sign of infection after 42 days of treatment . Lesions in the double-blind study, treated with nystatin, were healed after 28 days, whereas lesions that received placebo persisted throughout the treatment period . Increasing age, dry skin, and extended skinfolds at the corner of the mouth were factors closely related to the length of the healing process.

Genitourin Med, 1988 Oct, 64(5), 331 - 4
Vaginal candidosis: relation between yeast counts and symptoms and clinical signs in non-pregnant women; Hopwood V et al.; Of 277 non-pregnant women, 67 (24%) harboured Candida albicans in the genital tract . Of 56 women yielding C albicans who had no other infection diagnosed, 14 were symptomless and 10 had no clinical signs of vulval redness, vaginitis, or discharge . Symptoms and signs tended to be more severe in women with higher yeast counts . Of 22 women with moderate or severe symptoms (pruritus with or without discharge) and signs, 15 had yeast counts of more than 10(3) colony forming units (cfu)/ml, whereas six of nine women with no symptoms or signs had counts of fewer than 10(3) cfu/ml.

Br J Exp Pathol, 1988 Oct, 69(5), 651 - 60
Genetics of resistance to infection with Candida albicans in mice; Marquis G et al.; To determine differences in susceptibility, 234 naive mice including xid and beige mutants were infected intravenously with Candida albicans and monitored with survival analysis and quantitative culture of the kidneys . By using survival time as the criterion, animals of seven inbred strains were separated into three groups . C3H/HeJ and Dw/+ were most susceptible; C57BR/cdJ, BRVR and CBA/N (xid) were intermediate in susceptibility; C57BL/KsJ and C57BL/6J were least susceptible . Mean survival times (MST) were markedly influenced by the number of Candida cells injected while the ranking of mouse strains by survival alone was unchanged . There was a dissimilar behaviour of the strains to produce organ weight changes in response to infection when compared with uninfected mice which were matched for age and genetic lineage . Black mice had lower colony forming units (CFU) per mg of tissue at the time of death than animals of other genetic lineage . Nevertheless, the finding that MST and CFU studies were loosely correlated in a few strains of mice indicated that the proliferation of the fungus in the kidneys was not always the major cause of death . The beige mutation was found to determine an increased susceptibility to systemic Candida infection . The differences in survival for beige and nonbeige mice were influenced by the genetic lineage of the host, being much greater in the C57BL/6 strain (36.7 days) than in the C3H/He strain (5 days) . C57BL/6 beige-J had significantly higher CFU per organ and per unit of weight than C57BL/6 +/+ mice . These data evinced an important contribution of host genetic factors to resistance to systemic candidiasis . It is suggested that innate resistance genes regulate the differentiation in the bone marrow and the function of cells of granulocyte-macrophage lineage.

Mycopathologia, 1988 Oct, 104(1), 3 - 6
Experimental candidiasis associated with liver injury . Role of transferrin; Abe F et al.; In an attempt to perform a further investigation on the proposal that an increasing susceptibility to Candida infection in liver injury may be related to unsaturated transferrin level (UIBC) and/or to a total amount of transferrin represented by TIBC, we conducted experimental candidiasis using mice with galactosamine-induced liver injury and investigated the effect of preadministration of transferrin prior to inoculation of Candida albicans . Final mortality was 10% in the mice without liver injury and without transferrin (Group 1) and ones with liver injury and with transferrin (Group 3) . By contrast a 50% mortality was given in one only with liver injury (Group 2) . The TIBCs in Groups 1 and 3 were significantly higher than that in Group 2 . The UIBCs in Groups 2 and 3, although there was no significant difference between them, were significantly lower than that in Group 1 . This study confirmed that transferrin (TIBC) may have a direct deterring effect on systemic Candida infection and the decreased TIBC in the liver injury enhances the growth of C . albicans.

Immunology, 1988 Oct, 65(2), 181 - 5
Phagocytosis of heat-killed blastospores of Candida albicans by human monocyte beta-glucan receptors; Janusz MJ et al.; Candida albicans is an opportunistic human pathogen with a cell wall that is qualitatively similar in carbohydrate composition to zymosan . Monolayers of human peripheral blood monocytes ingested 2.5 x 10(6)-2.5 x 10(7) heat-killed C . albicans blastospores in a dose-related manner . The percentage of monocytes ingesting at least one C . albicans reached a near plateau level of 68 +/- 6% (mean +/- SD, n = 3) when 2.5 x 10(7) particles per ml were incubated with monocytes for 30 min . Pretreatment of monocytes with 10 ng/ml to 100 micrograms/ml of soluble yeast beta-glucan inhibited C . albicans ingestion in a dose-dependent manner without affecting Fc-mediated ingestion of IgG-coated sheep erythrocytes (EsIgG) . Pretreatment of monocytes with 100 micrograms/ml of soluble yeast beta-glucan inhibited the ingestion of 1 or more C . albicans by 80 +/- 11% (mean +/- SD, n = 4), with 50% inhibition occurring with approximately 7 micrograms/ml of soluble beta-glucan . Incubation of monocytes with 100 micrograms/ml to 1000 micrograms/ml of soluble yeast mannan resulted in no significant inhibition of C . albicans ingestion . The pretreatment of monolayers of monocytes for 30 min with 1 microgram/ml to 50 micrograms/ml of affinity-purified trypsin resulted in a dose-dependent inhibition of C . albicans ingestion with 10 micrograms/ml of trypsin inhibiting the percentage of monocytes ingesting 1 or more organisms by 71 +/- 6% . The inhibitory effects of soluble yeast beta-glucan and trypsin pretreatment on the ingestion of heat-killed C . albicans are comparable to the inhibitory effect of these agents on monocyte phagocytosis of zymosan and glucan particles . This relationship indicates that C . albicans contain a ligand that is recognized by the monocyte beta-glucan receptor of human monocytes.

Gene, 1988 Sep 7, 68(2), 229 - 37
Isolation of the gene for cytochrome P450L1A1 (lanosterol 14 alpha-demethylase) from Candida albicans; Kirsch DR et al.; The Saccharomyces cerevisiae cytochrome P450 L1A1 (lanosterol 14 alpha-demethylase)-coding gene was used as a hybridization probe to isolate two HindIII fragments of 2.5 kb and 6.85 kb from a phage lambda library of Candida albicans nucleotide sequences . Restriction endonuclease mapping and Southern blot hybridization experiments indicated that these fragments represent two allelic forms of the same gene . This cloned sequence, when introduced into S . cerevisiae or C . albicans on a multiple copy vector, produced an increase in cytochrome P450 content and resistance to imidazole antifungal agents which are inhibitors of cytochrome P450 L1A1 . In addition, the cloned sequence was able to complement a cytochrome P450 L1A1 gene disruption when introduced into S . cerevisiae . These data indicate that the cloned sequence codes for the lanosterol 14 alpha-demethylase cytochrome P450 L1A1 from C . albicans.

S Afr Med J, 1988 Sep 3, 74(5), 235 - 6
Treatment of Candida albicans meningitis with intravenous and intrathecal miconazole . A case report; Morison A et al.; Systemic fungal infection in an infant is difficult to diagnose and manage . The treatment is prolonged and is usually with toxic drugs . The use of intravenous and intrathecal miconazole (Daktarin; Janssen) in a small baby of 5 months was most satisfactory.

Am J Surg Pathol, 1988 Sep, 12(9), 716 - 20
Candida hepatitis . Histopathologic diagnosis; Johnson TL et al.; Candida hepatitis, usually a manifestation of disseminated candidiasis in immunocompromised patients, is difficult to diagnose antemortem . We studied six patients with proven hepatic candidiasis to assess features helpful in deriving a correct diagnosis . Five patients were immunosuppressed as a result for treatment for leukemia; one was immunosuppressed due to renal transplantation . All had sustained fevers greater than 101 degrees F, elevated alkaline phosphatase levels, and multiple hepatic and splenic defects--presumably abscesses--on abdominal CT scan . Twelve liver biopsies (nine needle, three wedge) were examined . Biopsies from four patients contained identifiable Candida organisms within suppurative granulomas; a biopsy from a fifth patient grew Candida albicans in cultures . In the sixth patient, the first biopsy was culture positive for Candida albicans, and the second biopsy, a fine-needle aspirate, contained Candida organisms and purulent material . In all of the nondiagnostic biopsies, as well as in regions of the diagnostic biopsies around the suppurative granulomas, mass-associated obstructive changes were noted . These included pericentral sinusoidal dilatation and cholestatic inflammation characterized by periportal ductular proliferation with surrounding neutrophils and edema . We conclude that in the appropriate clinical setting, these mass-associated histologic findings are suggestive of adjacent Candida abscesses . Definite diagnosis requires either the identification of Candida organisms within inflammatory hepatic lesions or positive culture of Candida from the liver biopsy.

Clin Exp Immunol, 1988 Sep, 73(3), 430 - 5
B lymphocyte activation in systemic lupus erythematosus: spontaneous production of IgG antibodies to DNA and environmental antigens in cultures of blood mononuclear cells; Dar O et al.; IgG antibodies to DNA, influenza virus haemagglutinin (HA), adenovirus hexon (HX) and mannan from Candida albicans (MN) have been determined in supernatants from 2-day unstimulated cultures of peripheral blood mononuclear cells from SLE patients and controls . Mean values were much higher in the SLE group, with from 20% (MN) to 85% (DNA) of patients giving values above the normal range . Although a significant correlation was observed between anti-DNA and anti-HA production, anti-HX and anti-MN showed no such correlations . The specificity of the ELISA assays was demonstrated by inhibition tests . It is concluded that a selective form of polyclonal activation in SLE results in the production of antibodies to foreign as well as to self antigens.

Farmaco {Sci}, 1988 Sep, 43(9), 693 - 704
Researches on antibacterial and antifungal agents . IX--Pyrrole analogues of bifonazole with potent antifungal activities; Massa S et al.; The synthesis and antifungal activities of pyrrole analogues of bifonazole are reported . Reduction of 4-nitrobenzophenone to the corresponding alcohol, reaction with phosphorus tribromide of the latter compound and condensation of the bromonitroderivative with imidazole led to 1-{alpha-(4-nitrophenyl)-4'-benzyl}-1H-imidazole . Hydrogenation of the nitro group to amino and reaction with 2,5-dimethoxytetrahydrofuran according to the Clauson-Kaas procedure afforded the pyrrole analogue of bifonazole . This compound and the related chloroderivative were also prepared by a similar pathway starting from 4-(1H-pyrrol-1-yl)benzophenone and its 4'-chloroderivative . Microbiological screening against Candida albicans and Candida spp showed 1-(alpha-{4-(1H-pyrrol-1-yl)phenyl}benzyl)-1H-imidazole to be the most active compound among the tested derivatives.

Acta Paediatr Scand, 1988 Sep, 77(5), 773 - 5
A syndrome of progressive pancytopenia with microcephaly, cerebellar hypoplasia and growth failure; Hreidarsson S et al.; A male infant with congenital thrombocytopenia, progressing to pancytopenia in the second year of life is presented . Other findings included microcephaly with cerebellar hypoplasia, growth failure of prenatal onset and severe psychomotor retardation . He died at 23 months of age from candida albicans septicemia . Laboratory studies and a postmortem examination failed to reveal any known etiology for his disorder, but parental consanguinity suggests a genetic basis with an autosomal recessive mode of inheritance . Hoyeraal et al . have previously reported two brothers with similar clinical and laboratory findings . It is proposed that the condition of these three patients should be considered as a separate syndrome of congenital pancytopenia, distinguished from other congenital myeloid dysplasias by the extramedullary findings.

J Gen Microbiol, 1988 Sep, 134 ( Pt 9), 2583 - 92
Immunomodulation by Candida albicans: crucial role of organ colonization and chronic infection with an attenuated agerminative strain of C . albicans for establishment of anti-infectious protection; Vecchiarelli A et al.; Intravenous inoculation of an attenuated agerminative strain of Candida albicans (PCA-2) of low virulence, but not of two other species of Candida of low virulence (C . parapsilosis and C . viswanathii) into CD2F1 mice conferred protection against the highly virulent microbes C . albicans CA-6, Staphylococcus aureus and Aspergillus fumigatus . To provide protection, a definite inoculum size (10(6) cells per mouse) resulting in organ colonization and establishment of a long-lasting chronic infection with PCA-2 was needed . An inoculum of 10(5) cells gave rise to transient kidney colonization whereas inocula greater than 10(6) cells led to acute septicaemia and eventual death . Chronic infection of mice following inoculation of 10(6) PCA-2 cells was accompanied by detectable mannoprotein antigen levels in the serum (30-70 ng ml-1) while specific antibodies did not appear until 14 d after inoculation, at which time low antimannan antibody was present (ELISA titre 1:40-1:80) . Chronic infection was characterized by the presence in the kidneys of 2-3 x 10(6) c.f.u . of PCA-2 for at least 40 d after inoculation . Pharmacological modulation of the host through administration of either an anti-Candida drug, amphotericin B, or an immunosuppressive agent, cyclophosphamide, strongly supported the premise that the anti-infectious state conferred by PCA-2 'immunization' correlated with the maintenance of a sufficient number of PCA-2 in vivo . Protection was 'switched on' when 2-3 x 10(5) cells were present in the kidneys . It was maximal at a kidney count of 2-3 x 10(6) c.f.u . of PCA-2, and promptly declined when the number of PCA-2 cells in the kidney fell below 2 x 10(5) . Mice chronically infected with PCA-2 had splenic macrophages with pronounced candidacidal activity in vitro . Modulation of the growth of PCA-2 in vivo, which determined activation or deactivation of the protective state, was paralleled by a similar modulation in macrophage activation, showing that in all cases resistance to virulent organisms persisted as long as macrophage activation was present . The results demonstrate that a critical in vivo antigenic load is crucial for the occurrence of resistance to infection and suggests that macrophages could be involved in this protection.

Ann Inst Pasteur Microbiol, 1988 Sep-Oct, 139(5), 547 - 55
{Effect of a subinhibitory dose of amphotericin B on cellular fatty acid and sterol composition of Candida albicans}; Mpona-Minga M et al.; Modifications in the cellular lipids of Candida albicans VW32 during its growth in the presence of a subinhibitory dose of amphotericin B were studied . Intracellular accumulation of fatty acids which appeared during growth was retarded in the presence of this antifungal agent after initial stimulation of unsaturated fatty acids . During the growth stage of the yeasts, sterols accumulated in cells through the action of amphotericin B . This accumulation was 80% during the growth state, but was only 13% in the stationary state . The relative level of ergosterol decreased through the action of this antifungal agent, but its precursors, namely ergosta-5,7-dien-3 beta-ol, episterol and fecosterol increased . The higher oxygenation of the cells due to the effect of this antifungal agent appeared to be responsible for the accumulation of unsaturated fatty acids and sterols in growing cells.

Pediatr Res, 1988 Sep, 24(3), 285 - 90
Human and rabbit newborn lung macrophages have reduced anti-Candida activity; D'Ambola JB et al.; Bronchoalveolar macrophages (BAM) protect the adult lung from low level microbial contamination . The antimicrobial activity of human newborn BAM is unknown . BAM were isolated from effluents of suctioned, intubated newborns and from bronchoalveolar lavage of healthy, nonsmoking adult volunteers . An in vitro cytologic slide assay was developed and used to ascertain: 1) inhibition of intracellular filamentation of Candida albicans (active yeast growth) and 2) killing + digestion of ingested C . albicans . The ability to restrict intracellular yeast filamentation was markedly different for human newborn versus adult BAM . Adult BAM were five times more effective in restricting intracellular filamentation of Candida compared to newborn cells (p less than 0.01) . Nonfilamented ingested yeast were also handled differently by newborn and adult macrophages . Nonfilamented yeast were killed and digested by adult BAM at a rate that was 2.5 times above that noted in neonatal lung macrophages (p less than 0.005) . However, no differences were found in the total number of killed + digested Candida within human newborn and adult BAM {adult = 32.4 +/- 10.5% (n = 5), newborn less than 1200 g = 39.6 +/- 16.8% (n = 8), and newborn greater than 1200 g = 30.2 +/- 11.1% (n = 16), mean +/- S.D.} . Neonatal BAM were able to destroy C . albicans at a level equivalent to adult cells because these newborn phagocytes allowed intracellular Candida to enter a state of active growth, thereby rendering the yeast more susceptible to killing and digestion . The anti-Candida activity noted in lung macrophages recovered from normal 1-day-old and adult rabbits was similar to that seen in human BAM.(ABSTRACT TRUNCATED AT 250 WORDS)

Mycopathologia, 1988 Sep, 103(3), 153 - 6
Enhancing resistance and modulation of humoral immune response to experimental Candida albicans infection by patulin; Escoula L et al.; Mice receiving patulin (10 mg/kg) from 1 to 4 days showed enhancing resistance to intraperitoneal challenge with 10(8) viable Candida albicans at day 2 . Resistance to C . albicans infection (10(6) blastospores) appeared to be unchanged after cyclophosphamide oral administration (60 mg/kg) . Immunoglobulins levels (IgA, IgM, IgG) are marked depressed (10 to 75%) in mice infected and/or treated by patulin and cyclophosphamide . The results show that an increase of neutrophil count may be among the factor underlying the late increase in resistance to C . albicans after administration of patulin.

Rev Infect Dis, 1988 Sep-Oct, 10(5), 1038 - 43
Fungal prosthetic arthritis: presentation of two cases and review of the literature; Lambertus M et al.; Fungal infections complicating reconstructive arthroplasty are extremely rare, with only six previously reported cases . These infections follow an indolent course and involve pain without inflammation in the affected joint, often as late as 2 years after surgery . Candida species other than Candida albicans are the commonest fungal pathogens and represent intraoperative contaminants . The diagnosis is made difficult by the indolent course and the frequent interpretation of the fungal isolate as a culture contaminant . Therapy requires resection of the prosthetic components with debridement; the additional need for antifungal therapy remains unclear.

Gastroenterol Clin North Am, 1988 Sep, 17(3), 451 - 63
Perspectives on gastrointestinal infections in AIDS; Janoff EN et al.; Gastrointestinal illnesses are among the most common and debilitating complication of infections with HIV, affecting 50 per cent to almost 100 per cent of AIDS patients in developed and developing countries, respectively . A number of factors including relevant modes of transmission, the environment, and immunosuppression conspire to determine which enteric infectious agents HIV-infected persons acquire . In developed countries, transmission of a diverse spectrum of bacteria, viruses, and protozoa is facilitated by unprotected receptive anal intercourse and anal-lingual contact among homosexual men with multiple partners . In developing countries, where most HIV infections occur among heterosexual persons, waterborne and foodborne transmission are the principal modes of transmission of enteric organisms . The severity and duration of symptoms associated with enteric pathogens are determined by the host's immunologic response to the organism . Candida albicans often causes local mucosal disease but less often causes systemic infections in HIV-infected persons, likely because polymorphonuclear cell function is intact . The ability of AIDS patients to control infections with G . lamblia and C . jejuni is related to their ability to mount an antibody response to these organisms during infection . The virulence of the organism may also affect the clinical response to infection . Cryptosporidium causes diarrheal symptoms in both immunocompetent and AIDS patients, but illness is more severe and prolonged in the latter . Giardia lamblia and C . jejuni infections are associated with a range of clinical manifestations in both AIDS patients and HIV-seronegative persons, whereas CMV and possibly adenovirus appear to cause significant disease only among immunocompromised subjects . The availability of effective therapy is among the most decisive factors in determining the duration of enteric infections in AIDS patients . For example, Giardia lamblia may cause acute abdominal pain and diarrhea in HIV-infected subjects but prolonged infections with the parasite are uncommon because effective therapy is available . In contrast, infections with CMV and Cryptosporidium may be severe and chronic as available therapy is generally ineffective or only transiently effective . Awareness of these clinical, epidemiologic, immunologic, and therapeutic aspects of gastrointestinal illness in HIV-infected subjects should help to direct the diagnostic evaluation of these patients and to direct areas of research.

J Leukoc Biol, 1988 Sep, 44(3), 166 - 71
Role of activated macrophages in resistance to systemic candidosis; Baghian A et al.; To evaluate further the contribution of activated macrophages in resistance, the course of systemic candidosis was assayed in beige and NLM mice that had been previously infected with Mycobacterium bovis (BCG) . Four weeks following BCG infection, mice were inoculated intravenously with 1 x 10(4) viable Candida albicans . At various times thereafter, the number of C . albicans colony-forming units in the livers, spleens, and kidneys was determined . The average number of CFU recovered from the kidneys of NLM mice decreased throughout the assay and was comparable in both BCG-treated and control mice . In contrast, the number of CFU cultured from the kidneys of untreated control beige mice progressively increased throughout the assay period . This profile of renal susceptibility was not appreciably altered in BCG-treated beige mice . However, fewer (10- to 100-fold) CFU were cultured from the livers and spleens of BCG-treated beige and NLM mice than from untreated controls . These results support the hypothesis that in the absence of functional polymorphonuclear leukocytes, activated macrophages represent a means to control the proliferation of C . albicans.

J Invest Dermatol, 1988 Sep, 91(3), 233 - 7
Characteristics of dermal invasion in experimental cutaneous candidiasis of leucopenic mice; Hahn BL et al.; The course of experimental cutaneous Candida albicans infections produced in mice made leucopenic by the administration of cyclophosphamide was compared to that in untreated animals . In the latter, neutrophils characteristically infiltrated the area of infection and the organisms were virtually always confined to the epidermis . However, even though many fewer foci of infection were associated with neutrophils in the cyclophosphamide-treated animals, a majority of these foci were also unable to penetrate past the epidermis . Although Candida yeast proliferated relatively poorly when cultured in homogenates of skin lacking the epidermis, Candida pseudohyphae could invade into the dermis if inoculated skin was isolated from normal animals and cultured in vitro, or if the epidermis was removed by gentle scraping prior to inoculation with Candida yeast onto the remaining skin of leucopenic animals . Therefore, in the absence of neutrophil contact and killing of Candida pseudohyphae in the epidermis, other cutaneous defense mechanisms appear to be capable of preventing invasion of a majority of the organisms into the dermis . These findings may help to explain why deep Candida infections are rare in patients who have extensive superficial candidiasis.

Infect Immun, 1988 Sep, 56(9), 2521 - 5
Dynamic expression of cell surface hydrophobicity during initial yeast cell growth and before germ tube formation of Candida albicans; Hazen BW et al.; Expression of cell surface hydrophobicity (CSH) during initial growth of Candida albicans was monitored . CSH of hydrophobic and hydrophilic yeast cells changed within 30 min upon subculture into fresh medium . Morphologic evidence of germination was preceded by expression of CSH . These results indicate that CSH expression is important in C . albicans growth.

Allergol Immunopathol (Madr), 1988 Sep-Oct, 16(5), 339 - 45
A study of the functions of polymorphonuclear neutrophil in patients with Down's syndrome; Rascon Trincado MV et al.; Patients with Down's syndrome (DS) are predisposed to infectious diseases, particularly of the respiratory tract . Together with the occurrence of cardiac defects, this is one of the main determinants of their life expectancy . The aim of the present work was to study a series of immunological parameters that would allow us to evaluate the functional behaviour of the neutrophil polymorphonuclears of the patients with trisomy 21 and the possible relationship between this and the susceptibility of this kind of patient to such infections . The results obtained point a significant decrease (p less than 0.001) in the adhesiveness index and in the two indexes relating to the evaluation of random mobilities of cells ("leading front" and "lower face of filter") . Although the neutrophil chemotactic responsiveness of these patients is decreased with any of the attractants employed (casein and activated sera), the differences observed with respect to the control population are more patent upon analyzing the function on the "lower face of filter" . Study of phagocytosis of Candida albicans and candidicidal activity of PMN reveals a normal behaviour in the presence of autologous (patient) and heterologous (control) serum . We propose that the alterations found in the PMN cell functions of DS patients could be due to intrinsic cellular defects and that this would help to explain why such patients tend to undergo repetitive infective processes.

Mol Gen Genet, 1988 Sep, 214(1), 24 - 31
One-step gene disruption by cotransformation to isolate double auxotrophs in Candida albicans; Kelly R et al.; The Candida albicans LEU2 gene was disrupted by substituting lambda DNA for a small deletion within the LEU2 gene . Cotransformation with a selectable URA3 ARS vector was used to introduce a linear fragment containing the disruption into the genome of a C . albicans ura3 deletion mutant . Cotransformants containing the lambda DNA were identified by colony hybridization and the URA3 plasmid was subsequently cured . Leu2 disrupted heterozygotes were detected by Southern hybridization and one disruptant was subsequently treated with UV irradiation . Only one leu2 ura3 mutant (SGY-484) was isolated out of 11,000 mutagenized cells . SGY-484 was transformed to Leu+ with either the C . albicans or Saccharomyces cerevisiae LEU2 gene . Southern hybridization analysis revealed that the mutant is not homozygous for the disruption; the leu2 mutation reverts and is most likely a point mutation . Unexpectedly, an ade2 ura3 mutant was isolated from the same mutagenesis.

Immunology, 1988 Sep, 65(1), 135 - 42
Human thymic dendritic cells . Characterization, isolation and functional assays; Landry D et al.; The phenotypic analysis of human thymic dentritic cells (DC) in culture and in purified suspensions has been studied with light and electron microscopic (EM) immunolabelling techniques . Using a series of monoclonal antibodies (mAb) and a protein A-gold technique, we demonstrated that DR- and T6-positive cultured DC strongly bind the 9.3F10 mAb, an anti-DR-related antibody produced against human blood DC, and weakly express the T4 antigen, a membrane marker shared by Langerhan's cells (LC) . On the other hand, thymic-cultured DC are negative for the other T-cell and monocyte-macrophage antigens . These results support the hypothesis that human thymic DC may be related to blood DC and epidermal LC . Moreover DC, unlike thymic macrophages, do not phagocytose latex particles, opsonized sheep red blood cells (SRBC) or Candida albicans . An efficient two-step technique of isolation, using a Percoll density gradient followed by an indirect panning technique, yields a purified (70-80%) thymic DC population, OKIa1-, 9.3F10- and OKT6-positive and esterase-negative . Immunolabelling and electron microscopy confirm that these isolated DC present similar phenotypic and ultrastructural features to human thymic DC in situ and in culture . Purified DC, used as stimulator cells in mixed leucocyte reaction (MLR), induce stronger proliferative responses than peripheral blood monocytes used as a control; blocking assays with OKIa1 mAb plus complement greatly reduced this stimulatory potency . These functional assays demonstrate that we obtained a purified typical DC population that can be used in immunological functional studies to elucidate the specific role of DC in human thymus.

Br J Dermatol, 1988 Sep, 119(3), 359 - 66
An evaluation of itraconazole in the management of onychomycosis; Hay RJ et al.; At present the reported use of itraconazole, a new oral triazole antifungal, has been confined to short-term treatments . This investigation is an appraisal of itraconazole in the treatment of three different forms of onychomycosis . Six patients with nail infections due to Candida albicans not associated with paronychia affecting a total of 20 nails received itraconazole (100 mg daily) for a mean period of 5.9 months . Complete remission was achieved in all cases . Twenty six patients with dermatophyte onychomycosis affecting a total of 45 finger and 80 toe-nails were treated with itraconazole (100-200 mg daily) . In 24 cases the causative organism was Trichophyton rubrum . Remission was achieved in 64% of finger and 73% of toe-nails in 5 and 9.4 months, respectively . Treatment failures were experienced in patients with finger-nail infections due to T . violaceum (I) and those concurrently receiving phenytoin and phenobarbitone (3) . Three patients with infections due to Hendersonula toruloidea failed to respond to treatment . Adverse effects were experienced by four patients (abdominal discomfort 3, diarrhoea I), but none were serious enough to lead to abandonment of treatment . No persistent changes were seen in serum biochemical values . This study suggests that itraconazole is potentially effective in the long-term treatment of superficial fungal infections such as onychomycosis, and comparative studies with alternatives such as griseofulvin should now be carried out.

Afr J Med Med Sci, 1988 Sep, 17(3), 167 - 70
Preliminary investigation of in-vitro antimicrobial activity of two Nigerian Diospyros species (Ebenaceae); Odelola HA et al.; The aqueous and alcoholic extracts from the leaves of Diospyros bateri and D . monbuttensis were studied for their antimicrobial activities . The alcoholic extracts of the two Diospyros spp . showed strong antibacterial activity against a wide range of Gram-positive and Gram-negative bacteria, while only the aqueous extract of D . bateri showed antibacterial activity against all the bacteria tested . The two fungi included in the study Aspergillus niger and Candida albicans were found to be resistant to the extracts of both Diospyros spp.

J Clin Microbiol, 1988 Sep, 26(9), 1720 - 4
Candida albicans- and Candida stellatoidea-specific DNA fragment; Cutler JE et al.; DNA was isolated from whole cells of Candida albicans and digested with MspI restriction enzyme . In addition to the expected large number of low-molecular-weight DNA pieces resulting from the digestion, multiple high-molecular-weight (greater than 3.0 kilobase pairs) fragments were generated by this enzyme, which cleaves DNA at CCGG sequences . Some of these fragments appeared highly repeated . An MspI fragment which was similar in size to one of the repeat elements (2.9 kilobase pairs) was cloned into the ClaI site of the plasmid vector pBR322 and replicated in a suitable Escherichia coli host strain . The candidal fragment was radiolabeled and used to probe Southern blots of DNA from several Candida species, various other fungi, and mouse and human cells . Only DNA from C . albicans and a strain of Candida stellatoidea was found to contain sequences of significant homology for hybridization . The cloned fragment may possibly be of use as a DNA probe for detection of the presence of C . albicans.

Biochem Biophys Res Commun, 1988 Aug 15, 154(3), 954 - 8
Effects of the detergent sucrose monolaurate on binding of amphotericin B to sterols and its toxicity for cells; Gruda I et al.; Amphotericin B (AmB) is a potent antifungal agent used to treat patients with systemic mycoses . The cytotoxicity of AmB is related to its binding to membrane sterols and its clinical usefulness is based on its greater affinity to ergosterol, the fungal sterol, compared to the mammalian cell sterol, cholesterol (1-3) . Here we report that sucrose monolaurate (L.S.) decreased the binding of AmB to cholesterol without interfering with its binding to ergosterol . Furthermore, the toxicity of AmB for mouse erythrocytes (RBC) and cultured mouse fibroblasts, L-929, cells was significantly decreased by low concentrations of L.S., whereas under the same conditions, its toxicity for Candida albicans was unaffected . We observed a very good correlation between the spectroscopic and cell studies . The results reported here on the effects of L.S . on the selectivity of AmB toxicity for fungal cells compared to animal cells and the relative nontoxic nature of sugar esters suggest a potential for compounds of this type to enhance the therapeutic index of AmB.

Infect Immun, 1988 Aug, 56(8), 2016 - 22
Stimulation of neutrophil actin polymerization and degranulation by opsonized and unopsonized Candida albicans hyphae and zymosan; Kolotila MP et al.; We previously showed that unopsonized Candida albicans hyphae stimulated a delayed rise in the putative neutrophil second messengers Ca2+ and inositol 1,4,5-trisphosphate and subsequent O2- release, as compared with opsonized hyphae or zymosan . Therefore, cytoskeletal and degranulation temporal responses to these stimuli were examined . Unopsonized zymosan elicited no neutrophil responses under the experimental condition used . Neutrophil actin polymerization (quantitated by fluorescent measurements of NBD phallacidin) was rapid after stimulation by opsonized hyphae or zymosan (peaking at 1 and 2 min, respectively) . This corresponded to observed changes in microscopic actin polymerization, measured with rhodamine phalloidin, which progressed from initially diffuse to collarlike to cylinderlike staining patterns surrounding the hyphae . Compared with opsonized hyphae, unopsonized hyphae resulted in a delayed appearance of the last two visible patterns (P less than 0.05) and in quantitative actin polymerization despite similarly rapid initial contact and spreading over the hyphae by neutrophils . Unlike other neutrophil responses, degranulation did not follow the delayed patterns of responses to stimulation with unopsonized hyphae . In the absence of the release of the cytoplasmic marker lactate dehydrogenase, the release of beta-glucuronidase, an azurophil granule marker, gradually and progressively rose in response to all of the stimuli but unopsonized zymosan . The low but significant levels observed were within a range consistent with published results for degranulation responses to particulate stimuli without cytochalasin B . A quantitative immunoassay of lactoferrin, a specific granule marker, detected no release into supernatants, and immunofluorescent staining indicated concomitant depletion of lactoferrin from neutrophil granules and binding to hyphal and neutrophil surfaces after stimulation by unopsonized hyphae . Thus, the delayed actin polymerization response to unopsonized hyphae occurred subsequent to neutrophil attachment and spreading and resembled the temporal sequence of other neutrophil responses linked to the respiratory burst . In contrast, the degranulation responses to all stimuli appeared to begin and progress gradually after observed attachment and spreading of the neutrophil over hyphal surfaces without a clear temporal relationship to rises in cytoplasmic Ca2+ or F-actin . In addition, the avid binding of released lactoferrin to cell surfaces eliminates its value as a quantitative marker of enzyme release but raises the possibility that it might participate in fungicidal activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Infect Immun, 1988 Aug, 56(8), 1987 - 93
Adherence of Candida albicans germ tubes to plastic: ultrastructural and molecular studies of fibrillar adhesins; Tronchin G et al.; Germ tubes of Candida albicans produced an additional fibrillar surface layer responsible for enhanced adherence to plastic . The correlation between germination of C . albicans and adherence of germ tubes to a plastic matrix led us to consider the existence of germ tube-specific adhesive components involved in the attachment process . Using concanavalin A-sensitized latex microspheres, we first detected extracellular molecules on the plastic surface after removal of the adherent germ tubes . Electron microscopy confirmed that fibrils of the germ tube involved in cell-substratum interconnections were retained on the plastic surface . Cytochemistry with concanavalin A-gold labeling demonstrated that these fibrillar structures contained mannoproteins . Dithiothreitol and iodoacetamide treatment of washed plastic allowed us to further characterize these fibrillar adhesins . Through analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, two components with molecular weights (MWs) of 68,000 and 60,000 were detected on the plastic surface . The 68,000-MW component appeared to be one of the major constituents of the germ tube surface layers . Biosynthetic labeling experiments performed with L-{35S}methionine revealed two additional proteins: a high-MW component (greater than 200,000), and a 200,000-MW component . These four proteins, strongly labeled on the plastic surface and on the germ tube cell wall layers, were in contrast slightly labeled or even nonidentified in the culture supernatant, suggesting their involvement in germ tube adherence.

Infect Immun, 1988 Aug, 56(8), 1942 - 9
Scanning electron microscopy of epidermal adherence and cavitation in murine candidiasis: a role for Candida acid proteinase; Ray TL et al.; Adherence of blastoconidia to epidermal corneocytes is an early event in Candida colonization and infection of the skin . Pathogenic species adhere more avidly than nonpathogenic species, transform to hyphal growth, and invade the stratum corneum of the skin . Adherence was studied by scanning electron microscopy of experimental murine cutaneous Candida infections, using six species of Candida . Candida albicans and C . stellatoidea blastoconidia, applied to newborn mouse skin, adhered to the stratum corneum in greater numbers than other species tested, acquired fibrils and strands of amorphous mucinlike material ("cohesin") between spores and the corneocyte cell surface, formed cavitations in the corneocyte surface, and invaded the corneocyte envelope by hyphal growth at sites distant to the point of blastoconidia attachment . Other species showed little or no adherence, colonization, or cavitation of the corneocyte surface, except C . tropicalis, which showed intermediate results . Pepstatin, an inhibitor of Candida acid proteinase, did not alter adherence or cohesion formation, but inhibited formation of corneocyte cavitations about adherent blastoconidia, suggesting that this enzyme may facilitate adherence/invasion events on skin . Depletion of surface lipids did not alter the formation of cohesin material or the adherence process . Adherence and invasion of epithelium by pathogenic Candida species include the interaction of blastoconidia with an epithelial surface cohesin material that participates in the adherence process . Candida acid proteinase, a keratinolytic enzyme, may participate in the cavitation process of the corneocyte surface by C . albicans.

Klin Monatsbl Augenheilkd, 1988 Aug, 193(2), 192 - 4
{Keratomycosis caused by Candida albicans}; Arocker-Mettinger E et al.; A 78-year-old female patient developed mycotic keratitis in her right eye three months after penetrating keratoplasty . Multiple myeloma is presumed to have been the predisposing factor . Candida albicans was isolated from the aqueous humor at the time of surgery . Treatment consisted of systemic ketoconazole (p.o.) and miconazole (i.v.); miconazole eye drops were applied topically and amphotericin B was instilled into the anterior chamber . Resolution of the corneal infection was ultimately achieved with this therapy.

Antimicrob Agents Chemother, 1988 Aug, 32(8), 1154 - 7
New class of antifungal agents: jasplakinolide, a cyclodepsipeptide from the marine sponge, Jaspis species; Scott VR et al.; Jasplakinolide is a cyclodepsipeptide which represents a new class of antifungal agents with potent activity against Candida albicans . Jasplakinolide is fungicidal against C . albicans with both a MIC and a minimum lethal concentration of 25 micrograms/ml in a broth dilution assay . This activity compares to that of the imidazole miconazole nitrate, which had a MIC of 6.2 micrograms/ml and a minimum lethal concentration of 50 micrograms/ml in the same assay . Topical administration of 2% jasplakinolide cream against a murine vaginal C . albicans infection was equivalent in efficacy to administration of miconazole nitrate at 2% . Subcutaneous administration of jasplakinolide was not effective against a systemic murine C . albicans infection.

Scand J Dent Res, 1988 Aug, 96(4), 360 - 5
Recurrence of angular cheilitis; Ohman SC et al.; The incidence of recurrence of angular cheilitis following a successful antimicrobial treatment was studied in 48 patients . Clinical assessments including a microbial examination were carried out 8 months and 5 yr after termination of treatment . Eighty percent of the patients reported recurrence of their angular cheilitis on one or more occasions during the observation period . Patients with cutaneous disorders associated with dry skin or intraoral leukoplakia had an increased incidence of recrudescence . Neither the presence of denture stomatitis nor the type of microorganisms isolated from the original lesions of angular cheilitis, i.e . Candida albicans and/or Staphylococcus aureus, were associated with the number of recurrences . The present observations indicate that treatment of the majority of patients with angular cheilitis should be considered in a longer perspective than previously supposed, due to the short lasting therapeutic effects of the antimicrobial therapy.

J Gen Microbiol, 1988 Aug, 134 ( Pt 8), 2393 - 403
Wall mannoproteins of the yeast and mycelial cells of Candida albicans: nature of the glycosidic bonds and polydispersity of their mannan moieties; Elorza MV et al.; Zymolyase released between 20 and 25% of the total protein from purified walls of yeast (Y) and mycelial (M) cells of Candida albicans . The material released contained 92% carbohydrate (86% mannose and 6% glucose) and 7% protein . Over 85% of the carbohydrate was N-glycosidically linked to the protein and the rest (less than 15%) was linked O-glycosidically . Highly polydisperse, high molecular mass mannoproteins, resolved by electrophoresis as four defined bands in Y cells and two bands in M cells, had both types of sugar chains . A 34 kDa species found in both types of cells had a single 2.5 kDa N-glycosidically linked sugar chain and a 31.5 kDa protein moiety . Polydispersity in the high molecular mass mannoproteins was due to the N-linked sugar chains (mannan) with a molecular mass between 500 kDa and 20 kDa (average 100 kDa) in Y cells and between 400 kDa and 20 kDa (average 50 kDa) in M cells . Three mannoproteins of 34, 30 and 29 kDa secreted by protoplasts were associated with the high molecular mass mannoproteins, suggesting that this type of interaction might be related to the regeneration of the cell wall.

J Gen Microbiol, 1988 Aug, 134 ( Pt 8), 2131 - 7
Effect of glucose and long-chain fatty acids on synthesis of long-chain alcohols by Candida albicans; White MJ et al.; Candida albicans, grown aerobically in glucose-containing media, produced C14, C16 and C18 saturated long-chain alcohols only after the end of exponential growth . Contents of C14 alcohols were always lowest, and C16 and C18 alcohol contents about equal . Contents of all three classes of alcohol increased as the concentration of glucose in aerobic cultures harvested after 168 h incubation was raised from 1.0 to 30.0% (w/v) . However, in 168 h anaerobic cultures, greatest long-chain alcohol contents in organisms were obtained using media containing 10% (w/v) glucose . Substituting glucose (10%, w/v) with the same concentration of galactose in aerobic cultures greatly decreased contents of long-chain alcohols, while inclusion of 10% (w/v) glycerol virtually abolished their synthesis . Supplementing anaerobic cultures with odd-chain fatty acids induced synthesis of odd-chain alcohols . Maximum conversion of fatty acid to the corresponding long-chain alcohol was observed with heptadecanoic acid . The effect of glucose on production of heptadecanol from exogenously provided heptadecanoic acid was similar to that observed on synthesis of the three major even-chain alcohols in media lacking a fatty-acid supplement . Cell-free extracts of organisms catalysed in vitro conversion of palmitoyl-CoA to 1-hexadecanol.

Hautarzt, 1988 Aug, 39(8), 498 - 503
{Pathomechanisms in Candida albicans infections}; Ollert M et al.; The adherence of the pathogen to the host cell is the first and decisive step in Candida albicans infections of the human organism . The mechanisms involved are mostly examined in human epithelial cells which are newly exfoliated and which therefore have a limited life expectancy . In this case, the glycoproteins on the cell surface of Candida albicans--mainly the mannan--are of central importance . They are the main component of the fungus to adhere to the host cell as well as to bind and activate the serum complement . Finally, the role of mannan in the interaction with host defence mechanisms is stressed.

Eur J Cell Biol, 1988 Aug, 46(3), 444 - 52
Ultrastructural localization of anionic sites on the surface of yeast, hyphal and germ-tube forming cells of Candida albicans; Horisberger M et al.; The cell wall of Candida albicans contains chitin, beta-glucans and phosphorylated mannoproteins, and possesses a fuzzy coat which is thought to play a role in pathogenicity, phagocytosis, and adherence of this dimorphic yeast . Using scanning electron microscopy and the gold method, mannoproteins were detected on the whole surface of blastoconidia including the bud scars, but chitin was absent even after alpha-mannosidase treatment of the cells . The presence of surface beta-(1----6)glucan (but not beta(1----3)glucan) was observed only after extensive alpha-mannosidase and alkaline phosphatase treatments of blastoconidia . Using transmission and scanning electron microscopy, the locations of anionic sites were revealed by polycationic colloidal gold-chitosan complexes on the surface of blastoconidia, germ tubes and hyphae . Anionic sites were dispersed evenly over the surface of blastoconidia bearing bud scars . Depending upon the growth conditions, anionic sites could be detected on emerging buds and young cells . However, bud scars were always free of marking . When germ-tube formation was induced, anionic sites were present at different densities on all cell surfaces, the highest density being observed on cells with bud scars . Anionic sites were detected at a remarkably high density on all hyphal surfaces . An apical concentration of anionic sites was observed on germ tubes and hyphae . The distribution of anionic sites was not modified by endoglucosaminidase treatment of blastoconidia, germ tubes and hyphae . The anionic sites were associated with the fuzzy coat . As the hyphal form is regarded as possessing the greatest invasiveness, it is suggested that anionic sites play an important role in establishing tissue colonization by this human pathogen.

J Am Acad Dermatol, 1988 Aug, 19(2 Pt 1), 275 - 9
Amoxicillin and diaper dermatitis; Honig PJ et al.; Multiple skin sites and the gastrointestinal tract of 57 infants with otitis media were cultured quantitatively for Candida albicans before and after antibiotic therapy . Ten days of systemic therapy with amoxicillin was associated with a twofold increase in the recovery of C . albicans from the rectum and skin . Infants who developed diaper dermatitis had a significant increase in the number of C . albicans organisms recovered from these sites . We conclude that the use of amoxicillin increases the risk for developing diaper dermatitis.

Infect Immun, 1988 Aug, 56(8), 1981 - 6
Candida albicans C3d receptor, isolated by using a monoclonal antibody; Linehan L et al.; Pseudohyphae of Candida albicans possess a receptor for C3d, a fragment of the complement component C3 . This receptor was partially purified by using a monoclonal antibody (CA-A) that previously had been shown to inhibit the binding of C3d to C . albicans pseudohyphae . Purified immunoglobulin G from ascites fluid (CA-A) was coupled to a cyanogen bromide-activated Sepharose column, and an affinity-purified fraction (A2) from C . albicans pseudohyphae was obtained . This fraction inhibited rosetting of the EAC3d receptor by pseudohyphae and appeared to contain glycoprotein, since receptor activity could be removed when A2 was incubated with lectins specific for mannose and glucose . A2 was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and two polypeptides of approximately 60 and 70 kilodaltons (kDa) were consistently identified in reducing gels . The 60-kDa protein was identified as a glycoprotein by concanavalin A binding . A2 was further analyzed by high-pressure liquid chromatography (HPLC) . Of three fractions obtained by HPLC, one containing the 60-kDa protein was found to have receptor activity . When analyzed by HPLC, this protein was found to contain mannose and glucose in approximately equal amounts . Both immunofluorescence and electron microscopy of pseudohyphae treated with CA-A identified A2 as a surface moiety . Thus, the C3d receptor of C . albicans, isolated with CA-A, is a glycoprotein of approximately 60 kDa.

Mycopathologia, 1988 Aug, 103(2), 91 - 4
Requirement for nonprotonated drug molecules in the direct lethal action of miconazole against Candida albicans; Beggs WH; At greater than or equal to 10(-5) M, miconazole (MCZ) can exert a direct physicochemical cell-damaging lethal action against logarithmic phase yeasts of Candida albicans . The imidazole moiety of MCZ has a pKa approximately 6.5 . Thus, in media of pH greater than 6.5 most drug molecules are nonprotonated (MCZ degrees) . Conversely, at pH less than 6.5 the majority are protonated and carry a positive charge (MCZH+) . Our earlier work suggesting that MCZ degrees is required for direct lethal action was tested further . In support of such a requirement, we established a minimal lethal concentration of MCZ degrees (i.e . 5 x 10(-6) M) that was relatively independent of pH, MCZ concentration, and MCZ degrees:MCZH+ ratio.

Scand J Dent Res, 1988 Aug, 96(4), 353 - 9
Crystalline inclusions in epithelial cells of hairy leukoplakia: a new ultrastructural finding; el-Labban N et al.; Hairy leukoplakia is often the first manifestation of an HIV infection . In the present study we have investigated the ultrastructural features of hairy leukoplakia in two HIV seropositive male homosexual patients . Ultrastructurally EBV particles were found in the upper prickle and keratinized epithelial cells, whereas papilloma virus particles were not found . Candida albicans were also seen in the keratinized layer . In addition two types of inclusions which have not previously been reported in hairy leukoplakia were commonly seen in the epithelial cells containing the EBV . The first was a crystalline microtubular structure which may take the form of several arrays . The second was an elongated multivesicular structure consisting of membrane-bound rounded vesicles embedded in a background of fine filaments . The vesicles were similar to the empty looking EBV particles and their mean diameter was 100 nm . Further investigations are needed to elucidate the exact nature of these structures and their relationship to the Epstein-Barr virus.

Lancet, 1988 Jul 30, 2(8605), 263 - 6
Candida and AIDS: evidence for protective antibody; Matthews R et al.; Clinical observation and animal models of candidosis suggest that, although T lymphocytes are important in preventing superficial candidosis, defence against systemic candidosis depends upon humoral immunity . An antibody response to the immunodominant 47 kD antigen of Candida albicans is invariably associated with recovery . The presence of this antibody in patients with chronic mucocutaneous candidosis and the acquired immunodeficiency syndrome (AIDS) could account for the rarity of disseminated candidal infection in these conditions . Polyclonal B cell activation may be responsible for the frequency with which this antibody is produced in AIDS . Antibody to the 47 kD antigen could be useful in the treatment and prevention of systemic candidosis, though not in the superficial candidosis of AIDS.

Biochem Biophys Res Commun, 1988 Jul 29, 154(2), 809 - 17
Candidacidal activity of myeloperoxidase: characterization of myeloperoxidase-yeast complex formation; Wright CD et al.; We have previously demonstrated the ability of human neutrophil myeloperoxidase to bind to cell wall mannan polysaccharide isolated from Candida albicans . This binding capacity provides for association of the enzyme with target yeast which is essential for efficient candidacidal activity . In this report, we further consider the role of the mannan-binding property of myeloperoxidase in the candidacidal activity of the enzyme . Solubilized mannan antagonizes binding of the enzyme to yeast, suggesting that mannan may be a primary component of the fungal cell wall which serves as a target for binding of myeloperoxidase . Myeloperoxidase is shown to form complexes with both solubilized mannan and Candida yeast, with Kds of 0.97 x 10(-5) M and 1.2 x 10(-5) M, respectively . The interaction between myeloperoxidase and mannan does not allow the enzyme to readily dissociate from the surface of target yeast . As a result, the enzyme may be unable to dissociate from dead yeast to become available for binding to additional fungal targets.

Presse Med, 1988 Jul 27, 17(28), 1430 - 2
{Effect of an immunomodulator, RU 41740, on experimental infections}; Joly V; RU 41740 is an immunomodulator of organic origin acting on cells of the immune system (B cells, T cells, phagocytic cells) and on mediators IL1-CSF) . Its mode of action has been explored by means of experimental infections . The types of defence involved differ according to whether the experimental infection is caused by an extracellular or intracellular micro-organism . Candida albicans and Saccharomyces cerevisiae were used to produce fungal infections, while bacterial infections were obtained with Staph . aureus, E . coli, Strep . pneumoniae and other organisms . The influenza virus was used to produce a viral infection . In these experimental models, RU 41740 increased the survival time of the infected animals and reduced bacterial, fungal and viral proliferation . These effects were observed even in immunocompromised mice . These in vitro and in vivo studies have demonstrated that RU 41740 is effective whatever the type of body defence involved.

Am J Obstet Gynecol, 1988 Jul, 159(1), 123 - 4
Intraamniotic infection with Candida albicans associated with a retained intrauterine contraceptive device: a case report; Smith CV et al.; Intrauterine infection with Candida albicans is a rare occurrence in pregnancy . We report the association of an intrauterine contraceptive device with such an infection in an asymptomatic patient . This infection, discovered incidentally at the time of genetic amniocentesis for advanced maternal age, resulted in a spontaneous abortion at 18 weeks' gestationPIP: Although intra-amniotic infection with Candida albicans rarely occurs during pregnancy, a recent review of 18 cases of antenatal Candida infection suggests an association with IUD use . The authors present a case of an asymptomatic 39-year-old woman (gravida 12, para 7, abortus 4) diagnosed incidentally at midtrimester amniocentesis with intra-amniotic infection . The woman reported a history of a Lippes Loop in situ for an unknown length of time . When amniocentesis was performed at 16 weeks gestation, due to advanced maternal age, the cell cultures were overgrown with Candida species and a repeat procedure was performed 3 days later to establish a viable cell culture for karyotype . 2 days after the 2nd procedure, the patient presented to the emergency room with spontaneous preterm rupture of the membranes . Amniorrhexis was confirmed, and the patient underwent pregnancy termination induced by prostaglandin E2 . There was histologic evidence of chorioamnionitis, and budding spores with pseudohypha consistent with Candida were observed in the placental fragments . It is postulated that bacterial contamination of the endometrial cavity at the time of IUD insertion was causal . The present case is unusual, however, in that the patient was asymptomatic and the diagnosis was made incidentally when the amniocyte culture was overgrown with yeast . This case suggests a need for careful counseling of women with an unretrievable IUD and coexistent pregnancy who do not manifest evidence of infection .

Infect Immun, 1988 Jul, 56(7), 1814 - 9
Association of electrophoretic karyotype of Candida stellatoidea with virulence for mice; Kwon-Chung KJ et al.; Seven isolates of Candida stellatoidea were studied for their electrophoretic karyotype, virulence for mice, sensitivity to UV radiation, growth rate in vitro, reaction on cycloheximide-indicator medium, and proteinase activity . The isolates exhibited one of two distinct electrophoretic karyotypes as determined by orthogonal field alternating gel electrophoresis (OFAGE) . Four isolates, including the type culture of C . stellatoidea, belonged to electrophoretic karyotype type I by OFAGE, showing eight to nine bands of which at least two bands were less than 1,000 kilobases in size as estimated by comparison with the DNA bands of Saccharomyces cerevisiae . These isolates failed to produce fatal infection in mice within 20 days when 5 X 10(5) cells were injected intravenously . The yeasts were cleared from the kidneys of two of three mice tested by day 30 . Type I showed proteinase activity on bovine serum albumin agar at pH 3.8 and produced a negative reaction on cycloheximide-bromcresol green medium within 48 h . The three grouped in type II by OFAGE showed banding patterns similar to those of a well-characterized isolate of Candida albicans . The isolates of type II had an electrophoretic karyotype of six to seven bands approximately 1,200 kilobases or greater in size . All three type II isolates were highly virulent for mice, producing fatality curves similar to those of a previously studied C . albicans isolate . From 80 to 90% of the mice injected with 5 X 10(5) cells intravenously died within 20 days . The type II isolates produced a positive reaction on cycloheximide-bromcresol green agar and showed no proteinase activity on bovine serum albumin agar at the low pH . In addition, the type II isolates grew faster and were significantly more resistant to UV irradiation than the type I isolates . These results indicated that type II, but not type I, isolates can be considered simply as sucrose-negative C . albicans.

Eur J Immunol, 1988 Jul, 18(7), 1143 - 6
Protection of neutropenic mice from lethal Candida albicans infection by recombinant interleukin 1; Van't Wout JW et al.; Natural and synthetic immunomodulators that increase nonspecific resistance to infection are also known to induce interleukin 1 (IL 1) production . Previous studies have demonstrated a protective effect of recombinant human IL 1 beta against death from infection caused by Pseudomonas aeruginosa . In the present study we investigated the effect of IL 1 beta or IL 1 alpha on the survival of neutropenic mice with a lethal Candida albicans infection . Mice with cyclophosphamide-induced neutropenia were injected with 3 X 10(5) C . albicans i.v . When 80 ng IL 1 beta was given as a single i.p . injection 24 h before the infection, survival compared to that in control animals was as follows: 100% vs . 97% at 24 h, 83% vs . 70% at 48 h and 70% vs . 23% at 72 h after the infection (p less than 0.01) . The effect of IL 1 was also apparent when it was given 1/2 h before or 6 h after the infection . The results obtained with 80 ng IL 1 alpha given at 24 h before infection were similar to that obtained with IL 1 beta . The numbers of Candida cultured from the blood, liver, spleen, and kidney were not significantly different in IL 1 beta-treated and control animals . Passive transfer of serum obtained from mice pretreated with IL 1 to recipient mice did not provide protection against a subsequent lethal candidal infection . In conclusion, the present study demonstrates that IL 1 beta and IL 1 alpha prolong survival in neutropenic mice with a lethal C . albicans infection.

Ann Inst Pasteur Microbiol, 1988 Jul-Aug, 139(4), 473 - 83
An investigation of the bactericidal and fungicidal effects of certain disinfectants by use of a capacity test; Hegna IK et al.; The bactericidal and fungicidal effects of five disinfectants and one combination of two disinfectants were tested using a modified Kelsey-Sykes method in which living microorganisms suspended in a sterilized yeast suspension ("dirty" conditions) and in sterile distilled water ("clean" conditions) were added to the disinfectants in three stages . Six bacteria and two fungal organisms were employed as test microbes . Results showed that formaldehyde was virtually inactive at the dilution tested (1/50), whereas phenol and the combination propylene-phenoxetol + benzalkonium chloride were moderately effective, the latter compound being better . Glutaraldehyde was manifestly the most effective of the disinfectants tested, followed by tricresol . At a 1/50 dilution, chloramine proved to have a surprisingly strong fungicidal effect on Candida albicans and Aspergillus fumigatus under "dirty" conditions, whereas the same fungal organisms proved rather resistant to chloramine under "clean" conditions . The same was demonstrated--though less markedly--when higher dilutions of chloramine were used . The search for an explanation is still in progress . At relatively high dilutions, chloramine also proved quite effective against most of the test bacteria, especially under "clean" conditions . It is recommended that the yeast suspension be replaced by normal horse serum 20% v/v when testing the efficacy of chloramine against fungal strains under "dirty" conditions.

Diagn Microbiol Infect Dis, 1988 Jul, 10(3), 171 - 9
Development of DNA probes for Candida albicans; Cheung LL et al.; An attempt was made to produce DNA probes that could be used as a rapid and efficient means of detecting candidiasis (invasive Candida infection) in immunocompromised patients . Whole DNA from Candida albicans was digested with restriction endonuclease, and the resulting fragments were randomly cloned into a plasmid vector . Several recombinant plasmids were evaluated for cross-hybridization to various other Candida species, other fungal DNAs, and to nonfungal DNAs . Cross reactions were observed between the probes and different yeasts, but none with unrelated DNAs . Some recombinants were genus-specific, and two of these were applied to the analysis of C . albicans growth curves . It became evident that, although both 32P- and biotin-labelled probes could be made quite sensitive, a possible limitation in their diagnostic potential was the poor liberation of Candida DNA from cells . Thus, better methods of treatment of clinical specimens will be required before such probes will be useful in routine diagnosis.

Rev Infect Dis, 1988 Jul-Aug, 10 Suppl 2, S423 - 7
Characterization of mannoproteins from a virulent Candida albicans strain and its derived, avirulent strain; Calderone RA et al.; Antigenic differences between a wild-type virulent strain of Candida albicans 4918 (wt) and its spontaneous avirulent mutant (m-10) were found with crossed-immunoelectrophoresis and western blotting . Mannoprotein fractions from yeast and mycelial forms were obtained by affinity chromatography on concanavalin A and analyzed with use of patient sera or sera from rabbits infected with live wt cells and boosted with whole extracts or rabbits immunized with purified wt cell wall preparations . A spike-formed precipitate was detected only with the wt yeast cells with crossed-electrophoresis and patient and rabbit sera . Otherwise serum from infected rabbits precipitated about equally the wt and m-10 cell wall mannoprotein antigens . The nature of this precipitate, with extremely slow electromobility in the first dimension and the possibility of its relation to some special immunodeterminant of the wt mannan molecule, is discussed . Likewise, when mycelial mannoproteins were analyzed by crossed-immunoelectrophoresis, a precipitate specific for wt cells was observed with rabbit anti-Candida sera . Also, a mannoprotein of approximately 47 kilodaltons was observed by western blotting only for wt mycelial cells . The observed antigenic differences between the virulent and the avirulent derived strain might be related to the greater adherence and infectivity of the wt strain.

What Is Bioassay?, What Is Pcr?, What Is Activated Sludge?, What Is Salmonella?, What Is Growth Medium?, n, Microbes, r, Microorganism, r, Bacteria, o, Microbiology, i, Bacteriology, r, Yeasts, s, Bacillus, s, Escherichia coli, a, Corynebacter, o, S. cerevisiae, e, Escherichia coli, c, Escherichia coli, r, Escherichia coli, a, Fermentations, i, Cell cultures, n, Staphylococcus aureus, c, Antimicrobials, n, Propionibacteria, s, Microbial, a, Staphylococcus, i, Bacillus, o, Escherichia coli, s, Escherichia coli, s, Escherichia coli, c, Proteus, e, Microorganisms

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

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

Last modified: May 25, 2005