Acta Obstet Gynecol Scand, 1984, 63(1), 85 - 9 The incidence of Candida albicans in the vagina of "healthy young women" . How often do they have symptoms? Possible etiological factors; Leegaard M; PIP: The frequency of vaginal Candida albicans was investigated in 603 healthy women at a contraceptive clinic . Swabs were taken from the rectum which is thought to be the reservoir and thereby the cause of reinfection of the vagina with Candida albicans . A neat correlation appears to exist . Women who have received antibiotics within the 3 months prior to the investigation have significantly more frequent bouts of candidosis . The same is true of pill users and for women using sanitary pads for menstrual protection, compared with those women using tampons only . The women were asked about bathing facilities and the frequency with which they use soap and water for washing the external genitalia . The latter indicated no difference, while there was an apparently increased frequency of positive swabs for Candida albicans in women who were spot washing, compared with those who took showers and baths . This difference was not significant . author's modified Folia Microbiol (Praha), 1984, 29(1), 23 - 34 Antimicrobial effects of esters and amides of 3-(5-nitro-2-furyl)acrylic acid; Kellova G et al.; The effect of 18 newly synthesized esters and amides of 3-(5-nitro-2-furyl)acrylic acid on bacteria (Escherichia coli, Staphylococcus aureus), yeasts (Saccharomyces cerevisiae, Candida albicans), molds (Aspergillus niger, Penicillium cyclopium, Rhizopus oryzae) and algae (Chlorella pyrenoidosa, Euglena gracilis, Scenedesmus obliquus) was investigated . The MIC values revealed antimycotic, antialgal and antibacterial activity of the studied derivatives . The antimycotic activity was found to decrease with increasing the length of the alkyl chain of esters and after introduction of amino nitrogen into the furylethylene backbone . The inhibitory effect on growth is caused by blocking bioenergetic processes, glycolysis in particular. Clin Neuropathol, 1984 Jan-Feb, 3(1), 37 - 41 Systemic Candida albicans infection with cerebral abscess and granulomas; Wietholter H et al.; This study reports the case of a 19-year-old Turkish woman who was suffering from a cerebral abscess and granuloma formation caused by Candida albicans . The diagnosis of her illness was established by cytologic analysis of the cerebrospinal fluid . Combined application of amphotericin B and 5-fluorocytosine cured the patient's disorder . Its remission was documented over a period of 2 years by the use of computed tomography. Ann Biol Clin (Paris), 1984, 42(6), 415 - 8 {Fungal infections: involved species and minimal inhibitory concentrations of common antifungal agents}; Dei-Cas E et al.; Fungal cultures of cutaneous or ungual origin (477 cultures), nasopharyngeal and urogenital origin (2,000 cultures), and blood, internal organs, surgical incisions, and catheters (300 cultures) were obtained in this study . Analysis of the data yielded the following information: Candida albicans and C . tropicalis, frequent causes of superficial or systemic mycoses, were very sensitive to flucytosine and amphotericin B in a liquid medium, but less sensitive to the imidazole derivatives; C . parapsilosis, a cause of superficial and systemic mycoses, was remarkably sensitive to all four antifungal agents tested; Torulopsis glabrata and C . krusei are of greatest concern in a hospital setting since systemic or visceral infections are minimally sensitive to antifungal agents; C . pseudotropicalis, C . guilliermondii, and C . zeylanoides are less pathogenic and sensitive to antifungal agents varies, depending on the strain . Specific measures are presented for management of fungal infections in a hospital setting . The role of antifungal susceptibility testing in everyday practice is also evaluated. Int J Tissue React, 1984, 6(6), 485 - 92 Combined effects of cyclophosphamide and thymostimulin treatment on the in vitro natural killer and candidacidal activity of murine spleen cells; Baccarini M et al.; Two different natural cell-mediated cytotoxic reactions (lysis of YAC-1 and killing of Candida albicans) in vitro were studied in mice undergoing treatment with cyclophosphamide (Cy), thymostimulin (TP-1) or a combination of both . Enhancing effects followed the combination regime in the microbial natural cell-mediated cytotoxicity assay, whereas in the NK assay the effect of TP-1 appeared to be antagonistic to that of Cy . The possible mechanisms involved are discussed. Ann Dermatol Venereol, 1984, 111(11), 1007 - 11 {Factitious crusting cheilitis}; Jeanmougin M et al.; The authors report 4 cases of factitious crusting cheilitis seen in young women . The lesions are crusty, yellowish or even black, forming as a mould casting the lip . The crusts are sometimes very thick just as an oyster-shell . When removed the underlying mucosa appears either normal or erosive and the crusts reappear rapidly . Emotional factors and personality disturbances are often present . Most probably the crusts are the result of a traumatic mechanism induced by chewing or sucking the lip . In the 4 reported patients the clinical aspect and the psychological status of the patients are similar, the 4 of them being not at all bothered by their cheilitis . The factitious keratotic cheilitis has to be differentiated from other cheilitis induced by Candida albicans (although Candida albicans may superinfect any cheilitis) or by an actinic phenomenon, from glandular cheilitis (of the Puente-Acevedo or of the Volkmann type) and from dermatitis localized on the lips . In some instances an exfoliative cheilitis may also to be of factitious origin . The factitious origin of such a cheilitis is always difficult to demonstrate but its possibility should be kept in mind. Ann Clin Res, 1984, 16(4), 201 - 3 Fatal Candida meningitis in a previously healthy adult; Sulkava R et al.; A rare case of fatal Candida albicans meningitis in a healthy middle-aged woman is reported . The organism did not grow in four of the six cerebrospinal fluid cultures despite clinical meningo-encephalitic symptoms and clear cell reaction in cerebrospinal fluid . Death was unexpected with a generalised tonic-clonic seizure and cardiac arrest . A possible relationship between the coexistent long-standing intra-uterine contraceptive device and Candida meningitis is discussed. Sabouraudia, 1984, 22(5), 409 - 18 A comparison of experimental pathogenicity of Candida species in cyclophosphamide-immunodepressed mice; Bistoni F et al.; The experimental pathogenicity of Candida albicans, C . krusei, C . guilliermondii, C . parapsilosis, C . tropicalis and C . viswanathii was tested in normal and in cyclophosphamide-(Cy) immunodepressed mice . In unpretreated CD1 mice only C . albicans, C . tropicalis and C . viswanathii were pathogenic on intravenous challenge, with LD50 of 1.0 X 10(6), 4.8 X 10(6), 7.2 X 10(8) cells, respectively, per kg . Three days after a single intraperitoneal injection of Cy (150 mg kg-1) mice had a marked decrease in spleen weight and cellularity as well as reduced numbers of circulating leukocytes . Under these conditions, there was a significant, proportional increase in pathogenicity of C . albicans, C . tropicalis and C . viswanathii but the animals were still resistant to challenge with C . krusei, C . guilliermondii and C . parapsilosis . This pattern of susceptibility was not influenced by higher doses of Cy . Only C . albicans and C . tropicalis were capable of rapid and extensive multiplication in target organs such as kidney and brain in normal and Cy-treated mice and for both these species of Candida, there was a 'rebound' effect of increased resistance to experimental infection after 12 days from Cy administration . This study shows that the strong immunodepression provoked by Cy does not modify significantly the susceptibility of the animal to those species of Candida which were endowed with low or no pathogenicity for normal mice, but it greatly increases the susceptibility to those species of Candida that are already pathogenic for unmodified host. Boll Ist Sieroter Milan, 1984, 63(6), 537 - 42 {Otomycosis: etiology and analysis of predisposing factors}; Oliveri S et al.; An otomycosis was found in 80 cases of external otitis on a total of 132 . Itching was the characteristic beginning, rapidly followed by pain, conductive hearing loss, tympanic perforation . Aspergillus was isolated in 81.7% of cases: in particular, A . niger in 67.1% of cases . A . flavus in 13.4% A . fumigatus in 1.2% . Candida albicans was isolated in 11% of cases . A statistical analysis based on chi 2 test was performed to evaluate the role of possible predisposing factors . Highly significant factors resulted to be working in gardens (P less than 0.005) or using mechanical removing devices . Not significant resulted to be swimming, water irrigations or antibiotic therapies: however infirmities were often not reliable . The above mentioned highly significant factors seem to be able to determinate the overlaying of otomycosis. Acta Haematol, 1984, 72(6), 379 - 83 Function of peripheral blood and bone-marrow monocytes in preleukemic patients: normal phagocytosis and intracellular killing of Candida albicans; Kletter Y et al.; Studies were performed to evaluate the function of peripheral blood and bone marrow monocytes from 15 patients with preleukemia and 16 healthy controls . The patients were grouped according to the criteria of the FAB collaborative group . No abnormality in phagocytosis and killing of Candida albicans by peripheral blood and bone marrow monocytes was found in patients compared to normal controls . Normal opsonization by autologous serum was found . No differences were found in this respect between the three groups of patients. Clin Exp Immunol, 1984 Jan, 55(1), 133 - 9 Resistance and susceptibility to infection in inbred murine strains . III . Effect of thymosin on cellular immune responses of alloxan diabetic mice; Salvin SB et al.; Three parameters of cell-mediated immunity, namely, (a) resistance to infection with Candida albicans, (b) in vivo release of migration inhibitory factor (MIF) into the circulation and (c) delayed hypersensitivity were markedly reduced when mice of such normally resistant high responder strains as C57B1/10SNJ and C57B1/KsJ became hyperglycaemic after treatment with alloxan . When the alloxan diabetic mice were inoculated daily intraperitoneally with thymosin fraction 5, beginning 3 days before infection, resistance to infection was greatly enhanced . When the mice were administered 5 micrograms thymosin fraction 5 for 3 days before sensitization and for 3 days before challenge, the amount of MIF released in vivo into the circulation after the antigenic challenge was much greater . When the mice were treated daily with 5 micrograms thymosin fraction 5, beginning on the day of sensitization, the capacity to develop delayed footpad reactions was increased . Thus, the treatment of alloxan diabetic mice with thymosin fraction 5 enhanced the three parameters of cell-mediated immunity that were under investigation. Cornea, 1984-85, 3(4), 285 - 7 Candida albicans transmission by penetrating keratoplasty; Stuart JC et al.; Transmission by microbial infection from donor to host during penetrating keratoplasty is of continuing concern to corneal transplant surgeons . Eye banks routinely use antibiotic and/or antiseptic solutions to pretreat donor eyes used for transplantation, but specific antifungal agents are not given . We report a case of Candida albicans endophthalmitis that occurred after using a donor eye found to have Candida positive cultures. Cancer Drug Deliv, 1984 Summer, 1(3), 199 - 205 Altered tissue distribution of amphotericin B by liposomal encapsulation: comparison of normal mice to mice infected with Candida albicans; Lopez-Berestein G et al.; Recently, it has been observed that encapsulation of Amphotericin B (Amp-B) into multilamellar vesicles (liposomes) decreases the toxicity associated with the administration of Amp-B, while maintaining its antifungal efficacy . In this study, the tissue concentrations of Amp-B in normal mice and in mice infected with Candida albicans were examined . Amp-B concentrations in various tissues were quantitated by high-performance liquid chromatography . Liposomal encapsulation improved the delivery of Amp-B to the liver, spleen, lung, and kidney in both normal and infected mice . Furthermore, after injection of the encapsulated drug, Amp-B was demonstrable in brain tissue of infected animals at potentially therapeutic concentrations . None was demonstrable in the brains of normal animals or animals injected with free Amp-B . The results suggest that capillary endothelial damage and phagocytic cell uptake may contribute to an enhanced liposome delivery of Amp-B to those organs most frequently infected with fungi. G Batteriol Virol Immunol, 1984 Jan-Jun, 77(1-6), 3 - 8 Candida contamination in renal transplant recipients: Candida albicans serotypes and sera-antibodies; Ghezzi MC et al.; Candida spp . is an important parasite for the immunocompromised host, and transplant recipients are at high risk for invasive and potentially lethal infections caused by this microorganism . The frequency of colonization at one or more sites and the correlation with humoral antibodies in renal transplant recipients have been studied . Candida strains were identified by cultural and biochemical tests, and moreover serological types of C . albicans were detected . Sera antibodies have been also determined by agglutination and immunodiffusion tests . Our results indicate that about 48.8% of patients had Candida spp . at one or more sites and these yeasts may be of different species or serotypes . None of the patients has had systemic candidiasis and none of them showed any convincing clinical or pathological evidence of invasive Candida disease. Dermatologica, 1984, 169 Suppl 1, 3 - 9 Bifonazole, a biochemist's view; Berg D et al.; Bifonazole, a new broad-spectrum antimycotic, interferes with sterol biosynthesis . Compared to clotrimazole, the primary mode of action of these two antimycotics is accepted to represent inhibition of the cytochrome P450-dependent hydroxylation at the sterol-C14-methyl group, which is the first step in C14-demethylation reaction . At least in dermatophytes bifonazole additionally inhibits directly HMG-CoA-reductase, the starting and regulatory enzyme in terpenoid biosynthesis, whereas after application of clotrimazole the activity of HMG-CoA-reductase is only decreased by feed-back control, resulting from accumulation of dihydrolanosterol . The inhibition of HMG-CoA-reductase obviously is pathogen specific as the mammalian enzyme is not affected . By this, in contrast to clotrimazole, bifonazole possesses a sequential mode of action, namely inhibition of cytochrome P450-dependent C14-demethylation of sterols and direct inhibition of HMG-CoA-reductase . In vitro bifonazole shows a strongly pH-dependent efficacy . The uptake kinetics of bifonazole have been measured with different pathogens . With respect to budding cells of Candida albicans it can be shown that the pH dependence of efficacy is due to a parallel pH dependence of the intracellular concentration of active ingredient . Even sublethal concentrations of bifonazole cause prior damages of young cells of C . albicans . These effects might explain the loss of infectivity of C . albicans after incubation with sublethal concentrations of bifonazole. Dermatologica, 1984, 169 Suppl 1, 11 - 8 Reduction of the in vivo virulence of Candida albicans by pretreatment with subinhibitory azole concentrations in vitro; Plempel M et al.; Cells of Candida albicans exposed to subinhibitory concentrations of clotrimazole or bifonazole in shake cultures were found to have a reduced capacity to divide normally or produce germ tubes and mycelia under appropriate conditions, although treated cultures produced a cell mass equivalent to that of the untreated controls . The long-term morphological effects are considered to be due to azole-caused disturbances in ergosterol biosynthesis . When cells, pretreated with subinhibitory concentrations of the azole compounds, were injected intravenously in mice, the resultant infections were of reduced severity in comparison to controls, as measured by mortalities and colony forming units in kidneys. Sabouraudia, 1984, 22(6), 505 - 7 Demonstration of a septal pore in budding Candida albicans yeast cells; Odds FC; Electron microscopy of Candida albicans yeast cells grown in a peptone glucose broth at 37 degrees C revealed pores in the septum identical in appearance to those already described in the hyphal form of the fungus . The presence of septal pores in yeast cells may explain apparently synchronous post-septation events in parent and daughter cells, and emphasizes the close structural similarities between different morphological forms of C . albicans. Sabouraudia, 1984, 22(6), 455 - 69 Histopathology of experimental systemic candidosis in guinea-pigs; Fransen J et al.; Unpretreated Albino guinea-pigs were infected intravenously with Candida albicans . Cutaneous candidosis with (pseudo-) hyphal outgrowth in the hair shafts and in the keratinized layers of the epidermis developed as a consequence of systemic dissemination . The spread of the infection was followed by cultures and by gross- and micropathological study of various organs of different animals during a follow-up period of 35 days . The possible relationship of organ invasion by C . albicans and skin candidosis is discussed. Mol Gen Genet, 1984, 198(1), 179 - 82 Isolation of the Candida albicans gene for orotidine-5'-phosphate decarboxylase by complementation of S . cerevisiae ura3 and E . coli pyrF mutations; Gillum AM et al.; A gene bank of Sau3A partially digested Candida albicans DNA in vector YEp13 was used to complement a ura3 mutation (orotidine-5'-phosphate decarboxylase, OMPdecase) in S . cerevisiae . Two plasmids which complemented ura3 and showed clear linkage of Ura+ and plasmid markers were selected for further study . Both plasmids also complemented the corresponding OMPdecase mutation (pyrF) in E . coli . Restriction mapping and subcloning studies localized the OMPdecase complementing activity to a region common to both plasmids . Probes prepared from this common region hybridized specifically to C . albicans DNA and not to E . coli or S . cerevisiae DNA . Southern blot analysis also showed that the restriction map of the ura3 complementing region of one plasmid was colinear with C . albicans genomic DNA . Expression of the OMPdecase complementing gene in E . coli and S . cerevisiae was not dependent upon orientation relative to vector sequences, suggesting that promotion could be occurring within the C . albicans fragment . Expression was sufficient to allow complementation in S . cerevisiae with integrating as well as high copy number vectors. Zentralbl Chir, 1984, 109(19), 1225 - 30 {Early recognition of fungal infection by detection of Candida albicans on catheter tips}; Dinger E et al.; The demonstration of Candida (C.) albicans from the tip of indwelling venous catheters may be regarded as a sign of contamination, colonization or Candida sepsis . Diagnostic and therapeutic possibilities in a district hospital are dealt with. Sabouraudia, 1984, 22(4), 351 - 4 The effect of 5-fluorocytosine on the temperature profile of Candida albicans; Lemos-Carolino M et al.; The temperature association of exponential thermal death with exponential growth, observed in a strain of Candida albicans, was disrupted by 5-fluorocytosine which, at a concentration of 2 micrograms ml-1, shifted the maximum temperature for growth from 38 degrees C to 33 degrees C but did not affect thermal death. Sabouraudia, 1984, 22(4), 315 - 21 Isolation of a Candida albicans mutant with reduced content of cell wall mannan and deficient mannan phosphorylation; Shimokawa O et al.; A rough-colony mutant of Candida albicans was isolated after ultraviolet mutagenesis . The mutant contained approximately half the normal amount of the cell wall mannan, the acetolysis pattern of which was indistinguishable from that of the wild-type counterpart . However, the extent of phosphorylation in the mutant mannan was about 12% of the value for wild type. Sabouraudia, 1984, 22(4), 265 - 71 IgA and IgG antibodies to Candida albicans in the genital tract secretions of women with or without vaginal candidosis; Gough PM et al.; Levels of anti-Candida albicans immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay in serum and cervicovaginal secretions from 64 non-pregnant women with vaginal candidosis and 158 uninfected non-pregnant women . Specific IgA and IgG were detected in the serum and secretions of all 222 women . There was no significant difference between the mean levels of specific IgA or IgG in secretions from women with candidosis and those of uninfected women . Neither was there a significant difference between mean levels of specific IgA or IgG when women using oral contraception were compared with others who were not . There was a significant correlation between the levels of IgA and IgG in serum and secretions from women with candidosis and from uninfected women . Blastospore and hyphal forms of C . albicans were seen in vaginal smears from 29 of the 64 women with culture-proven candidosis: in nine, both IgA- and IgG-coated C . albicans cells were recovered from the genital tract; in a tenth, IgG-coated cells were found. Cytobios, 1984, 40(157), 21 - 5 Plasmalemmasomes and lomasomes in Candida albicans; Rajasingham KC et al.; Candida albicans possesses plasmalemmasomes and lomasomes whose origin, structure and distribution are described . It is suggested that plasmalemmasomes become lomasomes during cell wall synthesis . The endoplasmic reticulum and lomasomes may be regarded as the functional equivalent to the Golgi apparatus in C . albicans and this view is discussed. Acta Microbiol Hung, 1984, 31(2), 81 - 4 Decreased permeability of glycerol in an ergosterol-less mutant of Candida albicans; Pesti M et al.; In a comparative study, an ergosterol-less nystatin-resistant mutant of Candida albicans and its ergosterol-producing nystatin-sensitive parental strain were investigated . The sterol mutant showed a more significantly decreased growth yield, respiration and glycerol-uptake activity than the parental strain as the consequence of its altered plasma membrane lipid composition. Sabouraudia, 1984, 22(3), 191 - 200 Correlative relationship between adherence of Candida albicans to human vaginal epithelial cells in vitro and candidal vaginitis; Segal E et al.; PIP: An attempt to determine whether a correlation exists between predisposition to candidal vaginitis and adherence of Candida albicans to vaginal epithelial cells in vitro is reported . Vaginal epithelial cells from 120 fecund women who were pregnant and/or diabetic had a greater propensity to bind C . albicans than did 71 oral contraceptive users and 75 nonpregnant, nondiabetic controls . The highest level of adherence occurred in pregnant diabetic women . Among 48 nondiabetic postmenopausal females, C . albicans adherence was lower than for fecund controls, but it was higher for cells from 33 postmenopausal diabetic women . The hormonal status of the fecund and postmenopausal women was assayed cytologically by the Karyopyknotic and Maturation Indices, which determine the ratios of superficial, intermediate, and parabasal vaginal epithelial cells . Findings point to increased C . albicans adherence in situations where there is and increase in the number of intermediate epithelial cells: pregnancy, the 1st or 4th weeks of the menstrual cycle, or diabetes . The adherence of 41 C . albicans isolates from patients with vaginitis was significantly higher than that of 36 isolates from asymptomatic carriers . author's modified Microbiol Immunol, 1984, 28(4), 393 - 406 The appearance and characterization of cyanide-resistant respiration in the fungus Candida albicans; Aoki S et al.; The respiration of yeast-form cells of the dimorphic fungus Candida albicans became resistant to cyanide during aging treatment in the resting state . An alternative, cyanide-resistant respiratory pathway was found to develop fully in cells aged at a concentration of 0.75 X 10(9)/ml or more at 25 C, but did not appear at 5 C . Chloramphenicol did not prevent the appearance of the alternative respiratory pathway . The effects of inhibitors, salicylhydroxamic acid (SHAM) and disulfiram (tetraethylthiuram disulfide), on respiration of aged cells were examined, and results indicated that SHAM binds at a site on the alternative respiratory pathway whereas disulfiram binds at two sites, one on the conventional respiratory pathway and the other on the alternative pathway . Thus, SHAM is a more selective inhibitor of the alternative respiration of C . albicans cells . SHAM-titration of the alternative respiration revealed that less than 10% of the maximal activity of the alternative respiratory pathway was utilized under normal conditions, indicating that the alternative respiratory pathway makes a small contribution to the total respiration . It was therefore concluded that the alternative, cyanide-resistant respiratory pathway operates fully when the cyanide-sensitive, cytochrome pathway is blocked although aged cells possess both respiratory pathways. Sabouraudia, 1984, 22(2), 137 - 44 A model for the germ tube formation and mycelial growth form of Candida albicans; Gow NA et al.; A model based on morphological and ultrastructural evidence is presented which illustrates a novel and hitherto undescribed pattern of germ tube formation and hyphal growth in early and mature colonies of Candida albicans . Accordingly, most of the cytoplasm within the parent yeast cell migrates into and forward with the extending germ tubes and leaves behind an extensively vacuolated yeast cell . Growing hyphae similarly are subtended by migrating "slugs' of protoplasm and leave behind vacuolated intercalary compartments . The vacuolated cell compartments apparently must first regenerate their protoplasmic contents before producing branches or secondary germ tubes . This model is used to explain certain unusual features of the growth kinetics of the filamentous form of this organism. Arzneimittelforschung, 1984, 34(2), 139 - 46 Bifonazole and clotrimazole . Their mode of action and the possible reason for the fungicidal behaviour of bifonazole; Berg D et al.; Bifonazole (Bay h 4502, Mycospor) and clotrimazole (Bay b 5097, Canesten) are potent inhibitors of ergosterol synthesis in yeasts and dermatophytes . Inhibition of demethylation of 4,4',14-trimethylsterols is accepted as primary mode of action responsible for their fungistatic efficacy . In Candida albicans, Microsporum canis, Trichophyton mentagrophytes as well as in Epidermophyton floccosum the ergosterol precursor 24-methylendihydrolanosterol accumulates, whereas in Torulopsis glabrata lanosterol accumulation occurs, due to the fact that in this organism side chain alkylation proceeds after demethylation reactions . Bifonazole additionally leads to a generally decreased rate of sterol biosynthesis as compared to clotrimazole, due to a direct inhibition of microsomal HMG-CoA-reductase . The additional fungicidal effects of bifonazole are considered to originate from a sequential action by inhibition of HMG-CoA-reductase and of cytochrome P450. Can J Microbiol, 1984 Jan, 30(1), 31 - 5 Comparative pathogenicity of auxotrophic mutants of Candida albicans; Manning M et al.; An induced mutant of Candida albicans with greatly decreased virulence for mice is described . The mutant was one of five auxotrophic mutants obtained by ultraviolet irradiation of a clinical isolate (strain MY 1044) . The five mutants included two methionine auxotrophs, one methionine-cysteine auxotroph, one temperature-sensitive serine auxotroph, and one auxotroph with unknown growth requirements . Each of the mutants produced normal mycelium and had a normal profile of susceptibility to four antifungal drugs . The virulence of each mutant was compared with the parent strain by LD50 determination in mice . Four of the five auxotrophs exhibited LD50's that were not significantly different from the parent strain (mean LD50 = 7.5 x 10(5) cells) . However, the temperature-sensitive serine auxotroph was significantly less virulent than the parent strain (LD50 greater than 10(7) cells), even though it grew well in vivo and in mouse serum at 37 degrees C in vitro . Use of this mutant in conjunction with its "isogenic" parent should help to elucidate true virulence factors in C . albicans. Am J Vet Res, 1984 Jan, 45(1), 87 - 90 Isolation and functional analysis of normal canine blood monocytes and resident alveolar macrophages; Shaw SE et al.; The percentage of mononuclear phagocytes bearing the Fc receptor for immunoglobulin G, the percentage of cells phagocytic for Candida albicans and latex particles, and the phagocytic index for blood monocytes and alveolar macrophages from healthy dogs are reported . Blood monocytes were concentrated by density-gradient centrifugation, whereas alveolar macrophages were obtained in high yield by bronchoalveolar lavage . Adherent populations of those cells were used for functional assays after repeated washing to remove nonadherent cells . A greater percentage of adherent alveolar macrophages than adherent blood monocytes showed evidence of the Fc receptor for immunoglobulin G . Similarly, adherent alveolar macrophages showed significantly greater phagocytic ability, as measured by percent phagocytic cells and phagocytic index, using C albicans and latex particles, than did adherent canine blood monocytes. Sabouraudia, 1984, 22(1), 83 - 5 Prevalence of different strains of Candida albicans in patients with denture-induced stomatitis; McCreight MC et al.; Eighteen resistogram strains of Candida albicans were found among isolates obtained from 10 oral sites sampled prior to treatment in 22 patients with denture stomatitis . Eight strains were isolated from single patients, but two were found in four patients and one was found in five patients . Fifteen of the 18 strains were isolated from sites including the fitting surface of the denture or the denture-bearing mucosa . Twelve patients, sampled on a second occasion after treatment, harboured at least one strain on both occasions. Scand J Infect Dis, 1984, 16(1), 43 - 50 Microbial colonization and infectious complications in bone marrow transplant recipients treated in strict protective isolation; Moller J et al.; Bone marrow transplantation was carried out in 10 patients (5 with acute leukemia and 5 with aplastic anaemia) . Protection against endogenous and exogenous infection was attempted by a rigorous sterile protective isolation regimen, comprising laminar-air-flow cabinets, daily decontamination of skin, mucous membranes and intestines . All supplies of food, fluids, medicine and equipment were sterilized . In all patients a heavy suppression of the normal bacterial flora was obtained after approximately 1 week and 85% of a total of 1026 days of decontamination revealed only scanty growth in one or a few regions of the patients . The surviving microorganisms were Candida albicans and non-pathogenic commensals (mainly Staphylococcus albus) . In 1 patient only an exogenic microorganism was introduced possibly by transfusion or staff . 16 febrile episodes were recorded in the patients during decontamination covering 21% of the period . Four episodes were caused by bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa and mixed) . In most of the remaining episodes the etiology was not established . The results thus show that endogenous pathogenic bacteria can be eradicated by the regimen, and that systemic antimicrobial chemotherapy can be restricted and guided by the results of the previous and contemporary cultures . However, viral infections remain a major problem in these patients . Efforts should be maintained to avoid entrance of exogenic bacteria by staff and supplies. J Fr Ophtalmol, 1984, 7(11), 689 - 95 {Favorable development of bilateral Candida albicans endophthalmitis . Value of early vitrectomy}; Furia M et al.; A chronic bilateral endogenous Candida albicans endophthalmitis in a heroin addict was treated by vitrectomy, argon laser photocoagulation and endodiathermy . In the left eye with a visual acuity of 6/6 there was a totally asymptomatic retinal tear due to vitreous traction . The eye was treated by argon laser photocoagulation immediately, and then underwent a vitrectomy several weeks later . Analysis of the vitrectomy specimen was negative for any organism . In the vitreous of the right eye a "fungus ball" was noted nasally . Visual acuity was also 6/6 . Fluorescein angiography demonstrated the presence of a small area of retinal involvement above the optic disc . During vitrectomy and membrane peeling the area of retinal involvement was torn away . The tear was then treated by endodiathermy . Vitreous analysis showed the presence of Candida albicans, sensitive to 5-fluorocytosine which was then used in treatment . All other cultures and stains were negative for Candida . The patient had negative serology for Candida, but normal immune responses based on cutaneous testing to several antigens and dosage of serum immunoglobulins and complement . A negative serology to Candida is most likely explained by the supposition that an episode of blood stream infection occurred only briefly and long before the eye involvement became clinically significant . At 4 months after bilateral vitrectomy, the patient has maintained 6/6 vision in each eye. J Fr Ophtalmol, 1984, 7(5), 413 - 7 {Retinopexy by endodiathermocoagulation}; Furia M et al.; Retinopexy was performed by endodiathermy coagulation around a retinal tear provoked during dissection of epiretinal membranes . The dissection was a complement to vitrectomy for Candida albicans endophthalmia . The choice of this technique was dependent on the absence of need for the laser, and allowed an internal buffering to be carried out by the use of silicone oil . Angiography showed depigmented areas confirming the presence of scar tissue as seen in experimental rabbit studies . The scar involved the whole thickness of the retina and choroid adjacent to the cauterized pigmented epithelium . This method is simple and possesses the advantage of being able to be used when the perioperative laser beam is unable to cross the transparent media of the eye. Sabouraudia, 1984, 22(1), 7 - 15 In-vitro studies with four new antifungal agents: BAY n 7133, bifonazole (BAY h 4502), ICI 153,066 and Ro 14-4767/002; Shadomy S et al.; Four new antifungal agents were compared in vitro with miconazole and ketoconazole . The agents were BAY n 7133 and ICI 153,066, two orally active triazoles, and bifonazole (BAY h 4502) and Ro 14-4767/002, both topical agents . While all four were found to be broad spectrum antifungal agents they also demonstrated certain gaps in their spectra . In general, Ro 14-4767/002 was the most active agent tested whereas bifonazole and BAY n 7133 were the least active . Noteworthy activities included that of Ro 14-4767/002 against Candida albicans, the dermatophytes and Sporothrix schenckii and that of ICI 153,066 against Torulopsis glabrata. Sabouraudia, 1984, 22(1), 53 - 63 Azole resistance in Candida albicans; Ryley JF et al.; Two isolates of Candida albicans from chronic mucocutaneous candidosis patients who initially responded to ketoconazole treatment but who later relapsed, have shown an abnormal response to ketoconazole in four out of five systems in vitro and in three animal models of vaginal or systemic infection . They have also shown abnormal resistance to inhibition of ergosterol biosynthesis in whole cells, but not in cell-free systems, and to inhibition of amino acid uptake . We conclude that the behaviour of the isolates is consistent with the development of drug resistance to ketoconazole . In all systems the two isolates have shown cross-resistance to the triazole antifungal ICI 153,066 . In addition they fail to take up radiolabelled ICI 153,066--in contrast to normal isolates--indicating that resistance is due to changes in the properties of the cell membrane rather than internal enzymology. Acta Med Scand, 1984, 215(1), 85 - 7 Hematogenous Candida spondylitis . A case report; Pohjola-Sintonen S et al.; A 58-year-old patient with neutropenia due to SLE developed spondylitis of the lumbar region caused by Candida albicans . The spondylitis was probably superinfected with Staphylococcus aureus . The initial one month's intravenous combination therapy with amphotericin B and flucytosine was discontinued because of fever reactions to amphotericin B, suspected myelosuppressive effect of flucytosine and insufficient clinical response . This therapy was followed by four months of oral ketoconazole and clindamycin with good results and without any side-effects. Antonie Van Leeuwenhoek, 1984, 50(4), 341 - 8 Glycogen synthesis by cell-free extracts from the dimorphic yeast Candida albicans; Orlean P; A particulate glucosyltransferase prepared from budding and filamentous cultures of Candida albicans used uridine diphosphate glucose as sole glucosyl donor in a reaction (measured by following the incorporation of {14C}-glucose from UDP {14C}-glucose into polymer) stimulated by glucose-6-phosphate and inhibited by adenosine triphosphate and guanosine triphosphate . The radiolabelled reaction product was solubilized by alpha-amylase, and, on oxidation with periodate followed by reduction with borohydride and acid hydrolysis, yielded erythritol and glycerol in the ratio of 4 to 1 . The radiolabelled glucosyl residues were attached to an endogenous acceptor of high molecular weight. Sabouraudia, 1984, 22(3), 175 - 83 Keratinolytic proteinase produced by Candida albicans; Hattori M et al.; Candida albicans was cultivated in various media that contained human stratum corneum, human scalp hair or keratin powder (cow's hoof) as a nitrogen source . Production of a keratinolytic proteinase (KPase) was observed when C . albicans was incubated in the medium containing stratum corneum . However, there was no production of a KPase that could digest human stratum corneum in the medium containing hair or keratin powder . alpha-fibrous protein extracted from human stratum corneum was digested by the KPase . The pH optimum of the enzyme was 4.0 and enzyme activity was inhibited by pepstatin A and chymostatin . The KPase, a kind of carboxyl proteinase, may be important for C . albicans to enable it to play a pathogenic role in vivo. Trans Am Ophthalmol Soc, 1984, 82, 447 - 91 The retinal lesions of the acquired immune deficiency syndrome; Friedman AH; AIDS is a reliably diagnosed disease that is indicative of an underlying cellular immunodeficiency with no other cause for the disorder . To date over 2000 cases have been reported in North America and Europe and the number is rising . Patients fulfilling the definition for AIDS have included male homosexuals, IV drug abusers of both sexes, people from Haiti, heterosexual partners of AIDS patients, hemophiliacs, and some patients who fit no particular pattern . The etiology has been attributed to factors acting singly or in synergy namely that repeated exposure to CMV, semen, or other antigens results in progressive cellular immunodeficiency, or alternatively, a novel virus has an etiologic role . The epidemiology of the syndrome suggests a horizontally transmissible agent . The spectrum of opportunistic infections observed in AIDS patients is well documented . A higher incidence of KS as well as squamous carcinoma of the oral cavity, cloacogenic carcinoma of the rectum, primary lymphomas of the brain, and systemic Burkitt's-like lymphoma has been noted . Seventy-one patients with AIDS were examined and followed during the course of their disease . Forty-one patients had definite retinal lesions at the time of examination . The most common intraretinal finding was CMV retinitis which displayed the typical white, crumbly areas of retinal necrosis and hemorrhage . Optic nerve involvement was quite common . The development of retinitis was a harbinger of eventual death as it was a progressive and a nontreatable disorder, lasting about 6 months . The second most common retinal finding was cotton wool spots, the lesions were usually present during the course of PCP and were due to microvascular damage in the retina from circulating immune complexes . No organisms were demonstrated in the retina . One AIDS patient who had been an IV drug abuser developed fungal retinitis due to Candida albicans . The patient eventually died from Candida sepsis . One patient had acquired toxoplasmosis retinochoroiditis . Examination revealed a large active intraretinal focus of infection . No other retinal lesion was noted . The patient, a homosexual, died from a toxoplasmosis brain abscess . The patient with AIDS is in a continuing struggle for survival against a myriad assortment of opportunistic infectious agents . Careful initial ophthalmological examination and long-term follow-up are mandatory. Ann Med Interne (Paris), 1984, 135(8), 669 - 71 {Severe candidiasis in heroin addicts}; Badillet G et al.; Seven cases of severe candida infection in heroin addicts are reported . The principal features of this condition which arose in 1980, apparently due to a particular quality of heroin, are described, Candida albicans was the only pathogenic agent isolated from mainly scalp nodular and pustular lesions . These cutaneous lesions were associated in half the cases with ocular lesions, which sometimes had a poor prognosis despite active therapy . Osteo-articular complications were less common . Ketoconazole therapy alone gave good results in this series . The precise reasons for this dissemination of Candida albicans and for these localisations are still not clearly understood. Sabouraudia, 1984, 22(4), 323 - 30 Oral ketoconazole therapy for experimental candida albicans keratitis in rabbits; Ishibashi Y et al.; Oral ketoconazole (100 mg daily for 3 weeks) markedly reduced the severity of experimental Candida albicans keratitis in a group of 10 rabbits . Clinical scores of affected eyes were statistically significantly lower in the treated group than in a control group of 10 untreated rabbits . All cultures of corneal scrapings in the treated eyes were negative on the 15th day after the inoculation, whilst three positive cultures were still obtained on the 21st day in the control animals . Histopathological examination of eyes from treated and untreated rabbits showed great differences in the intensity of inflammatory changes in the two groups. Microbiol Immunol, 1984, 28(8), 903 - 12 Protecting effect of chitin and chitosan on experimentally induced murine candidiasis; Suzuki K et al.; Chitin and chitosan were found to exhibit a protective effect on mice administered these polysaccharides intraperitoneally against infection of the viable cells of Candida albicans NIH A-207 strain . A significant difference was observed between the protective effects of chitin and chitosan, i.e., chitin was much more effective than chitosan when the C . albicans cells were challenged via the intravenous route . In intraperitoneal inoculations of C . albicans cells, however, chitosan provided stronger resistance for mice than chitin . It has also been revealed that the number of polymorphonuclear leukocytes from circulating blood of chitin-administered mice increased remarkably compared with that of untreated and chitosan-treated mice, and that the increase of active oxygen-generating phagocytic cells was significant . On the other hand, the number of peritoneal exudate cells (PEC) and the amounts of active oxygen generated from these cells in chitosan-treated mice were larger than those of chitin-treated mice . However, candidacidal activities of PEC per fixed cell number in mice treated with chitin or with chitosan were almost the same and greater than those of untreated mice. J Int Med Res, 1984, 12(5), 298 - 302 Topical tioconazole versus systemic ketoconazole treatment of vaginal candidiasis; Rohde-Werner H; A total of forty patients participated in an open, randomized study to compare the efficacy and toleration of a single dose of topical tioconazole 6% vaginal ointment with 5 days treatment of systemic ketoconazole (400 mg/day) in patients with symptomatic vaginal candidal infection . Disease in patients of both treatment groups was effectively eradicated after 5 weeks of therapy . Symptoms of patients receiving topical therapy responded more quickly than those of patients receiving oral therapy . Side-effects were more prevalent with ketoconazole systemic therapy . Overall, topical therapy with tioconazole was preferred over systemic ketoconazole therapy for these women with symptomatic vulvovaginitis due to Candida albicans. Chemotherapy, 1984, 30(4), 244 - 7 In vitro susceptibility studies with oxiconazole (Ro 13-8996); Gebhart RJ et al.; Oxiconazole (Ro 13-8996) is a recently described imidazole derivative intended for topical use . 128 isolates of pathogenic fungi were tested in vitro against oxiconazole, miconazole, and ketoconazole using an agar dilution method . Results indicated that miconazole was markedly more active than either oxiconazole or ketoconazole against Candida albicans while ketoconazole was the more active compound against Candida parapsilosis . A species specific difference in the susceptibilities of isolates of Aspergillus fumigatus and Aspergillus flavus to all three imidazoles with A . flavus being more susceptible was noted . Both Mucor and Rhizopus were more susceptible to oxiconazole than to either miconazole or ketoconazole . There were no noticeable differences among the dermatophytes in tests with the three drugs with all geometric mean minimum inhibition concentrations (MIC) being less than 1.0 micromilligram-1 . The dematiaceous fungi also demonstrated no major differences in susceptibility to the three drugs . One isolate of Pseudallescheria boydii was relatively resistant to all three drugs (MIC greater than or equal to 16 micromilligrams-1). Microbiol Immunol, 1984, 28(12), 1359 - 71 Antigenic relationship between Candida parapsilosis and Candida albicans serotype B; Funayama M et al.; We examined the antigenic relationship between Candida parapsilosis and C . albicans serotype B with respect to antigenic factors 13 and 13b, specific for the former species and common to both species, respectively . Acetolysis of C . albicans serotype B cell-wall mannan gave six oligosaccharides . Their chemical structure was determined by 1H-nuclear magnetic resonance (NMR) spectroscopy, methylation analysis, and partial acid hydrolysis . The structure of the hexasaccharide derived from C . albicans serotype B mannan was alpha-D-Manp-(1-2)-alpha-D-Manp-(1-3)-alpha-D-Manp-(1- 2)-alpha-D-Manp-(1-2)- alpha-D-Manp-(1-2)-D-Man (M6) which is identical to that from C . parapsilosis mannan . Inhibition of two precipitin reaction systems (anti-C . albicans serotype B serum and anti-C . parapsilosis serum to the respective homologous mannan), by oligosaccharides from homologous and heterologous mannans indicated that M6 from either C . albicans serotype B or C . parapsilosis was the most effective inhibitor . Moreover inhibition of the agglutination reaction between factor serum containing anti-factors 13 and 13b and C . albicans serotype B or C . parapsilosis cells by oligosaccharides from both mannans also indicated that the M6s were the most effective inhibitors . These results suggest that the M6s derived from the two species are identical in their chemical structure, although the structures of the whole mannans of the two species are not identical as demonstrated by gel diffusion precipitation patterns, and that M6s may be involved in the specificities of antigenic factors 13 and 13b . The amount of M6 is larger in C . parapsilosis cell-wall mannan, suggesting that high repeating frequency of M6 fragment may induce the antibody specific for C . parapsilosis. J Med Chem, 1983 Dec, 26(12), 1725 - 9 Transport of antimicrobial agents using peptide carrier systems: anticandidal activity of m-fluorophenylalanine--peptide conjugates; Kingsbury WD et al.; A series of di- and tripeptides containing D- and L-m-fluorophenylalanine was prepared and tested in vitro for the ability to inhibit the growth of the yeast Candida albicans . The results demonstrate that peptides containing L-m-fluorophenylalanine inhibited the growth of C . albicans with minimum inhibitory concentrations (MIC's) ranging from 0.5 to 63 micrograms/mL . The parent L-m-fluorophenylalanine and peptides containing D-m-fluorophenylalanine were inactive (MIC greater than 250 micrograms/mL) in these tests . The results of competitive antagonism studies support peptide transport mediated entry of the inhibitory peptides, followed by release of L-m-fluorophenylalanine inside the cell. Proc Natl Acad Sci U S A, 1983 Dec, 80(24), 7424 - 7 Thymosin alpha 11: a peptide related to thymosin alpha 1 isolated from calf thymosin fraction 5; Caldarella J et al.; Two peptides related to thymosin alpha 1 have been isolated from preparations of calf thymosin fraction 5 . One, lacking four amino acid residues at the COOH terminus, is designated des-(25-28)-thymosin alpha 1 . The other, named thymosin alpha 11, contains seven additional amino acid residues at the COOH terminus . The sequence of this peptide is: AcSer-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu- Lys-Glu-Lys- Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-Gly-Arg-Glu-Ala-Pro-Ala-AsnOH . Thymosin alpha 11, in doses of less than 300 ng per mouse, protects susceptible inbred murine strains against opportunistic infections with Candida albicans . It is approximately equal to 30 times as potent as thymosin fraction 5 and approximately equal in potency to thymosin alpha 1. Mycopathologia, 1983 Dec 1, 84(1), 41 - 4 Effect of yeast growth conditions on yeast-mycelial transition in Candida albicans; Bell WM et al.; When grown and induced to form germ tubes in liquid defined media, yeast cells of Candida albicans must reach stationary phase before acquiring ability to carry out the yeast-mycelial transition . This study examined the effect of the carbon source utilized for yeast growth on the inducibility of stationary phase yeast . When grown to the same stationary phase cell density as glucose cultures, cultures grown on citrate were fully inducible while cultures grown on galactose and mannose showed a small reduction . Cultures grown on ethanol were reduced 80% in morphological conversion . When glucose grown cells were induced in the presence of these carbon sources, hexoses supported full induction while ethanol reduced induction 80% . Induction in the presence of carboxylic acids was similar to induction in the absence of added carbon source . When induced on the same source used in yeast growth, germ tube formation was reduced for all carbon sources except hexoses . When induced in the absence of added carbon source, yeasts grown on citrate and ethanol were inhibited 80-100% . Cultures starved for glucose were more inhibited than cultures starved for NH4Cl when induced without added carbon source . These observations suggest that the metabolic state of the stationary phase cell is an important factor in the ability to respond to conditions inducing germ tube formation. Sabouraudia, 1983 Dec, 21(4), 271 - 86 Phagocytic killing of Candida albicans by different murine effector cells; Baccarini M et al.; Three major phagocytic populations in the mouse were tested in vitro for killing of Candida albicans by means of 51Cr release assay: early inflammatory peritoneal polymorphonuclear cells (PMN), unfractionated or adherent spleen cells and resident peritoneal macrophages (PEC) . Considerable candidacidal activity was found in the early inflammatory neutrophil and adherent spleen cell populations . On the contrary, only limited activity was found to be associated with resident peritoneal macrophages . The phagocytic killing apparently involved multiple mechanisms. J Lab Clin Med, 1983 Dec, 102(6), 960 - 72 Adherence of Candida albicans to buccal epithelial cells in children and adults; Cox F; Adherence of Candida albicans to BEC was determined in 20 children with oral candidiasis, 20 with oral colonization with C . albicans, and 40 uninfected controls not receiving antibiotics . Mean adherence was 15.3 +/- 0.08 yeast/cell in controls and significantly increased to 16.2 +/- 0.5 in colonized children (p less than 0.001) and 19.3 +/- 0.8 in children with oral candidiasis (p less than 0.001) . Adherence was the same in normal adults and children, suggesting a stable cell receptor system that is not age dependent . Adherence was also tested daily in 15 initially noncolonized, previously healthy children receiving antibiotics . Normally adherent background bacteria decreased significantly (p less than 0.004) on the first day of narrow- or broad-spectrum antibiotic therapy . C . albicans adherence increased significantly (p less than 0.004) on the second day . Oral colonization with C . albicans occurred on the third day of therapy . None of the children developed oral candidiasis over 3 to 9 days of observation . Healthy control children showed no change in adherence when tested daily for 1 week . Increased fungal adherence to BEC during antibiotic therapy may explain, in part, the increased incidence of Candida colonization in patients receiving antibiotics . Persistence of organisms may then permit disease to develop. J Bacteriol, 1983 Dec, 156(3), 1066 - 77 Genetic analysis of red, adenine-requiring mutants of Candida albicans; Poulter RT et al.; A number of investigators have described the isolation of red, adenine-requiring mutants of Candida albicans . Other fungi have been shown to give rise to two phenotypically similar, but genetically distinct, types of red, adenine-requiring mutants . This paper is the first indication that the red adenine mutants of C . albicans can similarly be resolved into two distinct classes . It is also believed to be the first report of such a resolution in an imperfect fungus . The resolution of these two classes was achieved by applying three distinct parasexual, analytical methods to this imperfect, naturally diploid yeast . The methods employed were complementation analysis of fused protoplasts and two methods of recombination analysis, induced mitotic crossing over in heterozygous revertants and induced mitotic crossing over in the heterozygous tetraploid products of protoplast fusion . The recombination methods depended on linkage analysis between the ade loci and two loci, met1 (methionine) and arg1 (arginine) . The three analytical methods supported the same resolution . The results support the generally accepted view that C . albicans is diploid since they indicate disomic inheritance at the ade1, ade2, and met1 loci. Am J Obstet Gynecol, 1983 Dec 1, 147(7), 809 - 11 Inhibition of Candida albicans--induced lymphocyte proliferation by lymphocytes and sera from women with recurrent vaginitis; Witkin SS et al.; To investigate whether there was an immunologic basis for recurrent Candida albicans-induced vaginitis, peripheral blood lymphocytes were isolated from six women with this disorder and from six healthy control women . No differences were observed in the proliferative responses of peripheral blood lymphocytes to mitogens . However, only the control peripheral blood lymphocytes proliferated in response to a C . albicans extract . Furthermore, patients' lymphocytes or serum suppressed the proliferative response of control lymphocytes to C . albicans but not to mitogens . Women with recurrent C . albicans vaginitis appear to produce Candida-specific suppressor lymphocytes which block the cellular immune response to this organism. Boll Ist Sieroter Milan, 1983 Nov 30, 62(5), 478 - 81 Management of candida peritonitis in a CAPD patient by flucytosine therapy: importance of drug level monitoring in body fluids; Giangrande A et al.; A case of Candida albicans peritonitis in a CAPD patient successfully treated with Flucytosine is reported . Flucytosine blood levels were monitored during intraperitoneal, intravenous and oral administration. Biochem Biophys Res Commun, 1983 Nov 30, 117(1), 43 - 50 Ketoconazole binds to the intracellular corticosteroid-binding protein in Candida albicans; Stover EP et al.; Ketoconazole is a broad-spectrum, orally-active antifungal agent that has been shown to inhibit sterol synthesis in susceptible fungi . We have previously demonstrated the presence of an intracellular protein in several Candida species that binds mammalian corticosteroids with high affinity . In this paper we report that ketoconazole competitively displaces {3H}corticosterone from the Candida corticosteroid-binding protein at concentrations readily achieved in therapeutic settings . Ketoconazole was at least 50-100 times more potent than structurally related imidazole compounds . Additional data suggest, however, that the binding of ketoconazole and related drugs to this Candida protein is not critical for the in vitro antifungal activity of these drugs. Mycopathologia, 1983 Nov 25, 83(3), 161 - 8 Cell-mediated immunity following experimental vaccinations with Candida albicans ribosomes; Levy R et al.; The aim of the present study was to ascertain whether cell-mediated immunity (CMI) is induced in animals by vaccination with Candida albicans ribosomes . Delayed type hypersensitivity (DTH) was detected in vivo in ribosome-vaccinated mice and guinea pigs by the footpad swelling and skin tests, respectively . The observed DTH was similar to that induced by live C . albicans organisms . A lymphocyte transformation assay was used for in vitro detection of CMI . The tritiated thymidine incorporation assays revealed that spleen lymphocytes from mice immunized with C . albicans ribosomes were stimulated by the ribosomal antigen . The findings establish that C . albicans ribosomes are able to induce CMI in experimental animals. Mycopathologia, 1983 Nov 21, 83(2), 97 - 102 Ultrastructural features of phagocytosis and intracellular killing of Candida albicans by mouse polymorphonuclear phagocyte monolayers; Richardson MD et al.; Phagocyte monolayers provided a simple method of following ultrastructural events associated with phagocytosis and intracellular killing of Candida albicans . Preformed monolayers of mouse polymorphonuclear (PMN) phagocytes attached to glass coverslips were incubated with blastospore phase C . albicans and then examined by scanning and transmission electron microscopy . Scanning electron microscopy revealed phagocytosis of C . albicans by mouse phagocytes . Ingestion of the organism was facilitated by the production of lamellipodia by the phagocytes . Transmission electron microscopy revealed complete phagocytosis of C . albicans and the fusion of lysosomal granules with loose and tight phagosomes . Ingested C . albicans remained structurally intact after 2 hr incubation in blastospore-free medium . However, cytoplasmic alterations were clearly evident, with a patchy loss of electron density . Alterations of the blastospore cell wall were also observed, with complete disruption of the plasma membrane but the wall remaining morphologically intact. Mycopathologia, 1983 Nov 21, 83(2), 87 - 95 Effects of growth temperatures on plating efficiencies and stabilities of heterokaryons of Candida albicans; Sarachek A et al.; Heterokaryons (hets) of Candida albicans constructed by fusing protoplasts of complementing auxotrophs produce heterogeneous clones on minimal medium consisting of (i) a minority of slow-growing hets, (ii) a preponderance of non-growing, parental-type auxotrophic monokaryons, and (iii) some prototrophic monokaryons bearing hybrid nuclei . Hets grown at a given temperature within the range 25 degrees C to 41 degrees C replate with higher efficiencies at any lower temperature and exhibit progressively declining plating efficiencies as plate temperatures increase beyond that at which they were initially grown . Neither auxotrophic nor prototrophic monokaryons show such responses . Growth of colonies produced by hets, wild-type strains or prototrophic hybrid monokaryons is stimulated by temperatures in the order, 37 degrees C greater than 30 degrees C greater than 41 degrees C greater than 25 degrees C . However, the proportion of hets to auxotrophic monokaryons within individual het clones increases directly from 25 degrees C to 41 degrees C . Though this pattern obtains whether colonies are compared at equivalent sizes or ages, het frequencies decline as colonies age at all temperatures . Appearance of hybrid monokaryons within het clones is unaffected by growth temperature . The relationships of temperatures to plating efficiencies and stabilities of hets are independent of the natures of their complementing auxotrophies or the wild-type backgrounds of their nuclear components and are, therefore, functions of heterokaryosis per se . Modifications of these relationships by selective metabolic antagonists or by growth of hets on different pre- and post-plating carbon sources indicate that they reflect temperature-dependent properties of mitochondria which are peculiar to hets. Klin Wochenschr, 1983 Nov 15, 61(22), 1137 - 9 {UV irradiation of the peritoneal dialysis solution for the prevention of peritonitis}; Tolon M et al.; Micro-organisms causing peritonitis during peritoneal dialysis or CAPD can reach the peritoneal cavity either along the Tenckhoff-catheter or via contaminated dialysis fluid . Laboratory experiments with UV irradiation of artificially contaminated CAPD fluid were made to demonstrate whether decontamination could be achieved during the flow through a UV-penetrable (lambda 2537 A) section of the CAPD catheter . Five CAPD bags were contaminated with a fluid culture of the following micro-organisms which frequently cause peritonitis (S . epidermidis, S . aureus, P . aeruginosa, E . coli, and Candida albicans) . After UV irradiation positive cultures could not be demonstrated . UV irradiation of the peritoneal dialysis fluid before entering the peritoneal cavity is proposed as an additional preventive measure. Arch Microbiol, 1983 Nov, 136(2), 114 - 6 Toxicity of 5-thioglucose towards a pathogenic yeast, Torulopsis glabrata; Arnold WN; 5-thioglucose (T-glc) caused premature death of T . glabrata cells after 1- and 2-day culture in defined glucose-containing medium . T-glc equilibrated with 80% of the cell water but did not accumulate in resting or growing cells . The sulfur analog had little or no effect on, 1) the rate of glucose uptake, 2) the kinetics of endogenous trehalose turnover preceding new growth, and 3) the viability of resting cells . A hallmark of cells grown in the presence of T-glc was the retention of abnormally high concentrations of glycogen after 2-day culture . Toxicity of T-glc towards Candida albicans and C . tropicalis was also indicated. Am Rev Respir Dis, 1983 Nov, 128(5), 909 - 14 Pulmonary tissue resistance to Candida albicans in normal and in immunosuppressed mice; Nugent KM et al.; We characterized the clearance of Candida albicans from the lung using a murine model for pulmonary aspiration . Swiss Webster mice uniformly survived intratracheally administered boluses of C . albicans (1 to 30 X 10(5) colony-forming units of yeast) which killed the majority of mice (more than 85%) when injected intravenously . Clearance studies, using quantitative cultures of lung homogenates, demonstrated rapid elimination of C . albicans from the lung after a 6-h delay; the residual fractions of viable fungi were 8.3 and 0.7% of the initial inoculums at 24 and 48 h, respectively, after inoculation . The number of leukocytes in the bronchoalveolar spaces increased twofold to threefold after deposition, and this primarily reflected a neutrophil influx . Histologic studies supported the bronchoalveolar lavage results and revealed a diffuse interstitial neutrophilic infiltrate and clusters of inflammatory cells in air spaces at 6 and 24 h after Candida deposition . Examination of lavage pellets demonstrated that both neutrophils and macrophages ingested C . albicans in vivo . Immunosuppression (orally administered prednisolone for 2 wk) delayed the clearance of C . albicans from the lung . However, evaluation of neutrophil migration into bronchoalveolar spaces and of the in vivo ingestion capacity of both macrophages and neutrophils did not identify differences that could explain this delayed clearance in steroid-treated mice . The fungicidal activity of pulmonary leukocytes was measured with in vitro assays and was similar in phagocyte cultures from control and steroid-treated mice . In summary, intrinsic pulmonary defense factors and recruited neutrophils rapidly and completely clear C . albicans from the lung after bolus deposition.(ABSTRACT TRUNCATED AT 250 WORDS) Antimicrob Agents Chemother, 1983 Nov, 24(5), 725 - 30 Bacteriostatic and fungostatic action of catecholamide iron chelators; Bergeron RJ et al.; Iron starvation as a means of controlling the proliferation of microorganisms was evaluated in vitro with spermidine catecholamide iron chelators . The growth of Escherichia coli and Pseudomonas aeruginosa was sensitive only to (D,L)-parabactin, whereas the growth of Candida albicans and Staphylococcus aureus was sensitive to a variety of catecholamide chelators . The disappearance of catecholamide activity upon methylation of the catechol hydroxyls, as well as iron reversal experiments, strongly suggests that the mechanism by which these compounds suppress growth is dependent upon their ability to sequester iron. Antimicrob Agents Chemother, 1983 Nov, 24(5), 787 - 96 Synthesis and biological activity of tripeptidyl polyoxins as antifungal agents; Naider F et al.; Three tripeptidyl polyoxins were synthesized and found to inhibit Candida albicans . Compared with the naturally occurring polyoxin D, the three synthetic polyoxins had little effect on chitin synthetase when assayed with a C . albicans membrane preparation . However, all the compounds inhibited growth, affected cell morphology in a manner similar to that of polyoxin D, and were hydrolyzed by cell extracts of C . albicans . Hydrolysis did not occur extracellularly, and at least one of the synthetic polyoxins, leucyl-norleucyl-uracil polyoxin C, inhibited peptide uptake, suggesting entrance into the cell via the peptide transport system . Thus, the intact tripeptidyl polyoxins are inactive prodrugs that are converted to active moieties by cellular enzymes. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1983 Nov, 255(4), 524 - 36 On the role of proteinases from Candida albicans in the pathogenesis of acronecrosis; Ruchel R; Evidence is presented for the involvement of proteinases from Candida albicans in the pathogenesis of acronecrosis that occurred in a young woman and which coincided with Candida sepsis . Secretory acid Candida proteinase by immunofluorescence was traced in the obstructed blood vessels of necrotic skin that was infested with yeast . The specificity of immunofluorescence was proven by exclusion of cross reactivity with pepsin, cathepsin-D, acid erythrocyte proteinase and porcine renin . The possible molecular mechanisms of interference of fungal proteinases are discussed with respect to the renin-angiotensin system and blood coagulation. J Antibiot (Tokyo), 1983 Nov, 36(11), 1539 - 42 Papulacandins--the relationship between chemical structure and effect on glucan synthesis in yeast; Rommele G et al.; Papulacandin B inhibits glucan biosynthesis in cells of Saccharomyces cerevisiae and Candida albicans . Biological studies with a series of papulacandin derivatives showed that the short fatty acid chain and the galactose residue are not required for activity at the target site, but that they can affect penetration . On the other hand, the long fatty acid residue is essential for biological activity. Antonie Van Leeuwenhoek, 1983 Nov, 49(4-5), 457 - 69 Cell wall composition and protoplast regeneration in Candida albicans; Elorza MV et al.; The transition of blastospores to the mycelial phase in Candida albicans was induced after the blastospores were kept at 4 degrees C for several hours and then transferred to a fresh medium prewarmed at 37 degrees C . Glucan was the most abundant polymer in the wall in the two morphogenetic forms but the amount of chitin was higher in the mycelial form than in blastospores . Efficient protoplasting required reducing agents and proteases together with beta-glucanases (zymolyase) . Protein synthesis in regenerating protoplasts was initiated after about 30 min . Chitin synthetase, initially very low, was incorporated in important amounts into cell membranes mainly in a zymogenic state . After a few hours chitin was the most abundant polymer found in the aberrant wall of the regenerating protoplast. Am J Clin Pathol, 1983 Nov, 80(5), 692 - 6 Improved recovery of microorganisms from patients receiving antibiotics with the antimicrobial removal device; Peterson LR et al.; Three hundred thirty-seven paired sets of blood cultures and ten sets of body fluid cultures from patients receiving antimicrobials were processed simultaneously by conventional methods with and without the use of an antimicrobial removal device (ARD) over a 13-month period of time in order to compare recovery rates . Forty-two significant pathogens were recovered: 19 by ARD processing only, four by conventional testing only, and the remaining 19 by both methods of processing . (P less than 0.001) . Seventeen patient samples contained antimicrobics not active against the blood isolate (mainly Candida albicans) . There was no difference (P greater than 0.1) between ARD-assisted and conventional methods in rate (frequency of cultures that were ultimately positive) or rapidity of detection of these microorganisms . In 17 subjects receiving antimicrobials active, in vitro, against the isolated microorganism, use of the ARD displayed a superior rate of recovery compared with conventional processing (P less than 0.001) and more rapidly detected organisms found both with and without ARD processing (P less than 0.04) . Contamination rate was 3.7% for use of ARD compared with 0.6% without ARD (P less than 0.01) . The ARD is a useful addition to conventional blood culture processing when used in a population of patients already receiving antimicrobial agents. J Allergy Clin Immunol, 1983 Nov, 72(5 Pt 1), 487 - 94 Delayed cutaneous hypersensitivity in normals: choice of antigens and comparison to in vitro assays of cell-mediated immunity; Gordon EH et al.; In 81 normal subjects, ages 19 to 100 yr (mean 52), we studied the prevalence of positive 48 hr skin reactions to six antigens: fluid tetanus toxoid, Candida albicans, SK/SD, Trichophyton, PPD, and coccidioidin . Of these, C . albicans was most frequently reactive (92%); SK/SD (51%) and tetanus (49%) were less so . Each of the remaining three antigens was reactive in less than 42% of the subjects . The minimum number of antigens required to detect delayed hypersensitivity in 100% of subjects was two: C . albicans and tetanus . We found no correlation between skin reactivity at 20 min, 6 hr, and 48 hr for most of the antigens studied, suggesting different mechanisms for reactions occurring at each time . In 60 of the subjects, lymphocyte stimulation index (LSI) with tetanus toxoid and monocyte chemotaxis (MC) assays were done . The natural log of the area of induration at 48 hr after tetanus skin testing (I48) increased as a function of LSI (p less than 0.005) and MC (p less than 0.025) by multiple regression analysis . Skin testing was less sensitive than LSI as a test for cell-mediated immunity in our population . However, because of availability and correlation with LSI, delayed cutaneous hypersensitivity should be tested initially . For this purpose, tetanus toxoid appears to be a useful antigen when used in combination with C . albicans. J Clin Invest, 1983 Nov, 72(5), 1629 - 38 Depression of the lymphocyte transformation response to microbial antigens and to phytohemagglutinin during pregnancy; Brunham RC et al.; Lymphocyte transformation (LT) responses to Chlamydia trachomatis, to four other microbial antigens, and to phytohemagglutinin (PHA) were studied in 201 women during pregnancy and/or 3-18 wk postpartum . The LT responses to all stimulants tested were significantly depressed during pregnancy when compared with postpartum LT responses . This difference occurred whether LT assays were performed in autologous or pooled heterologous plasma collected from nonpregnant donors . Among women studied in the third trimester and again postpartum, the autologous LT stimulation index (LTSI) rose from 1.7 to 3.4 (P less than 0.001) with C . trachomatis elementary body antigen, from 3.7 to 7.9 (P less than 0.001) with Candida albicans cell wall extract, from 4.5 to 7.8 (P = 0.008) with streptokinase-streptodornase, from 1.7 to 3.0 (P = 0.007) with fluid tetanus toxoid, from 1.7 to 2.8 (P = 0.046) with mumps virus skin test antigen, from 35.5 to 87.0 (P less than 0.001) with PHA (2 micrograms/ml), and from 107.2 to 181.9 (P = 0.007) with PHA (10 micrograms/ml) . LT responses to C . trachomatis were compared in 52 pregnant women and 58 nonpregnant women; all the women had C . trachomatis isolated at the time of LT assay . Using either plasma supplement, the mean LTSI with C . trachomatis antigen was significantly higher in nonpregnant women than in pregnant women, regardless of trimester (P less than 0.001) . Among 12 women who were serially tested and remained culture positive for C . trachomatis throughout pregnancy and the postpartum period, the mean autologous LTSI rose from 1.9 in the third trimester to 7.8 postpartum (P = 0.0004) . These data are the first to show that the immune response to an ongoing bacterial infection is depressed during pregnancy and to definitively document the depressed LT responses during human pregnancy. J Bacteriol, 1983 Nov, 156(2), 498 - 506 Conservation of genetic linkage in nonisogenic isolates of Candida albicans; Poulter R et al.; A number of laboratories are now engaged in the genetic analysis of Candida albicans . This diploid yeast, the major fungal pathogen of humans, is imperfect . Parasexual techniques have been devised for complementation and recombination analysis in this organism . This paper attempts to address the question of the extent to which nonisogenic strains of C . albicans have conserved a common genetic map . This analysis is a prerequisite for the integration of work done in different laboratories and may also provide useful information on the taxonomy of the genus Candida . The paper also reports the analysis of an interspecific hybrid between C . albicans and Candida stellatoidea . The method employed in these studies was the analysis of the mitotic recombination relationships of a group of linked genes and their centromere . Strains carrying linked auxotrophic mutations were fused with isogenic and nonisogenic complementary strains to form tetraploids . The mitotic recombination analyses of these tetraploids suggest that in the isolates studied the genetic map is conserved . A comparison of tetraploid and diploid mitotic recombination analyses is also presented. Can J Microbiol, 1983 Nov, 29(11), 1514 - 25 An analysis of the metabolism and cell wall composition of Candida albicans during germ-tube formation; Sullivan PA et al.; The uptake of nutrients (glucose, glutamine, and N-acetylglucosamine), the intracellular concentrations of metabolites (glucose-6-phosphate, cyclic AMP, amino acids, trehalose, and glycogen) and cell wall composition were studied in Candida albicans . These analyses were carried out with exponential-phase, stationary-phase, and starved yeast cells, and during germ-tube formation . Germ tubes formed during a 3-h incubation of starved yeast cells (0.8 X 10(8) cells/mL) at 37 degrees C during which time the nutrients glucose plus glutamine or N-acetylglucosamine (2.5 mM of each) were completely utilized . Control incubations with these nutrients at 28 degrees C did not form germ tubes . Uptake of N-acetylglucosamine and glutamine was inhibited by cycloheximide which suggests that de novo protein synthesis was required for the induction of these uptake systems . The glucose-6-phosphate content varied from 0.4 nmol/mg dry weight for starved cells to 2-3 nmol/mg dry weight for growing yeast cells and germ tube forming cells . Trehalose content varied from 85 nmol/mg dry weight (growing yeast cells and germ tube forming cells) to 165 nmol/mg weight (stationary-phase cells) . The glycogen content decreased during germ-tube formation (from 800 to 600 nmol glucose equivalent/mg dry weight) but increased (to 1000 nmol glucose equivalent/mg dry weight) in the control incubation of yeast cells . Cyclic AMP remained constant throughout germ-tube formation at 4-6 pmol/mg dry weight . The total amino acid pool was similar in exponential, starved, and germ tube forming cells but there were changes in the amounts of individual amino acids . The overall cell wall composition of yeast cells and germ tube forming cells were similar: lipid (2%, w/w); protein (3-6%), and carbohydrate (77-85%) . The total carbohydrates were accounted for as the following fractions: alkali-soluble glucan (3-8%), mannan (20-23%), acid-soluble glucan (24-27%), and acid-insoluble glucan (18-26%) . The relative amounts of the alkali-soluble and insoluble glucan changed during starvation of yeast cells, reinitiation of yeast-phase growth, and germ-tube formation . Analysis of the insoluble glucan fraction from cells labelled with {14C}glucose during germ-tube formation showed that the chitin content of the cell wall increased from 0.6% to 2.7% (w/w). Lancet, 1983 Oct 15, 2(8355), 873 - 8 Acquired immunodeficiency syndrome with severe gastrointestinal manifestations in Haiti; Malebranche R et al.; 29 patients (19 males and 10 females) in Haiti were diagnosed as having acquired immunodeficiency syndrome . Their clinical presentation was characterised by unexplained chronic diarrhoea, prolonged fever, extreme weight loss, anorexia, and severe infections . The infectious agents included: Candida albicans (27 patients), Mycobacterium tuberculosis (7 patients), Cryptosporidium (11 patients), Pneumocystis carinii (2 patients), cytomegalovirus (4 patients), and herpes virus (3 patients) . In 1 woman Kaposi's sarcoma developed during the course of her disease . Immunological studies of 20 patients revealed profound cell-mediated immune deficiency with cutaneous anergy, marked decrease in the number of T helper cells, and impairment of lymphocyte proliferation . 18 patients died. Helv Paediatr Acta, 1983 Oct, 38(4), 351 - 60 {Combination of a Shwachman syndrome and a complex granulocyte function disorder in a girl}; Dopfer R et al.; We report the case of a 1-year-old girl with the typical symptoms of Shwachman syndrome: neutropenia, insufficiency of the exocrine pancreas, and metaphyseal dysostosis . The clinical course is complicated by recurrent infections caused by the neutropenia and an additional defect of granulocyte function . We demonstrate a severe defect of chemotactic activity as well as a disturbance of the intracellular oxidative metabolism leading to defective killing of Staphylococcus aureus and Candida albicans. Pediatr Res, 1983 Oct, 17(10), 814 - 20 A mechanism for liver cell injury in viral hepatitis: effects of hepatitis B virus on neutrophil function in vitro and in children with chronic active hepatitis; Vierucci A et al.; Neutrophil function was studied by nitroblue tetrazolium (NBT) reduction, superoxide anion (O2-) production, chemotaxis, and bactericidal activity in 9 children with HBsAg-positive chronic active hepatitis (CAH) . NBT reduction and O2- production were higher in resting neutrophils from the children with CAH than from the controls, but the production of O2- was depressed after stimulation with zymosan . No defect was observed in both random and direct locomotion, whereas a significant decrease was present in bactericidal activity . To evaluate the role of virus components, purified preparations of HBsAg and HBcAg were added to neutrophils from normal children . The incubation with such products induced in vitro the same modifications that were observed in the neutrophils from children with CAH . In addition, defects in phagocytosis and killing of Candida albicans as well as in chemotaxis were demonstrated . The production of O2- was reduced in the neutrophils, stimulated by zymosan and previously opsonized with HBsAg-positive serum. Am J Hosp Pharm, 1983 Oct, 40(10), 1650 - 3 Microbial growth patterns in intravenous fat emulsions; Keammerer D et al.; Microbial growth patterns were studied in intravenous fat emulsions under conditions that simulated touch contamination before or during administration . Commercially available emulsions of 10% and 20% soybean oil and 10% safflower oil in 500-ml bottles were inoculated with two concentrations of each of four organisms: a coagulase-negative Staphylococcus isolated from a venipuncture site, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans . The bottles were kept at room temperature, and samples were taken by direct puncture of the i.v . port at 0, 3, 6, 12, 24, 48, and 72 hours, diluted, and plated . Emulsions were visually inspected daily . Growth of the coagulase-negative Staphylococcus was minimal for 48 hours . E . coli showed substantial growth within 12 hours in all three emulsions . Growth patterns for Ps . aeruginosa were similar in all emulsions, and growth approximated that of E . coli within 48 hours . The growth rate of C . albicans was intermediate between that of Staphylococcus and those of E . coli and Ps . aeruginosa . Growth of C . albicans was greater in 10% safflower oil emulsion than in the other emulsions . No physical changes were observed . The coagulase-negative Staphylococcus showed less growth than C . albicans, Ps . aeruginosa, and E . coli . Substantial growth within 12 hours was seen only with E . coli . C . albicans exhibited preferential growth in 10% safflower oil emulsion. Can J Microbiol, 1983 Oct, 29(10), 1438 - 44 Cell wall proteins of Candida albicans; Chaffin WL et al.; Proteins were solubilized from cell wall fractions of Candida albicans and separated by polyacrylamide gel electrophoresis . Cell walls were isolated from 25 and 37 degrees C growing and stationary phase yeast cultures and from germ tubes . The 42 protein bands detected by dye binding were observed in all wall extracts, regardless of the temperature, growth state, or morphology of the culture . The carbohydrate content of most bands was below the detectable limit of the periodic acid Schiff reagent . The protein complement revealed by autoradiography of radiolabeled proteins was half that detected by staining . Two bands showed greater intensity from cultures grown at 37 degrees C . The radio-labeled pattern was similar with both {35S}methionine-and {14C}leucine-labeled proteins and either pulse- or continuous-labeled proteins. J Gen Microbiol, 1983 Oct, 129 (Pt 10), 3001 - 6 Effects of culture density on the kinetics of germ tube formation in Candida albicans; Ahrens JC et al.; The relationship between culture density or phase of growth at 24.5 degrees C and the ability of Candida albicans to form germ tubes when shifted to 37 degrees C was investigated . Evidence is presented demonstrating germ tube production from liquid synthetic medium cultures at all phases of growth . Previous studies reported that only cells from stationary phase cultures were competent to form germ tubes . Comparisons between exponential and stationary phase cultures indicate more rapid and more synchronous germ tube production from cells growing in the exponential phase. Antibiotiki, 1983 Oct, 28(10), 747 - 51 {Morphofunctional features of cells of Candida albicans upon interaction with a polyene antibiotic}; Araviiskii RA et al.; Changes in the volume, mass and concentration of the dry matter in the cells of Candida albicans during 48-hour incubation with various doses of amphotericin B were studied with the use of a polarization interference microscope (BIOLAR, Poland) . The changes of the parameters studied had a wave-like pattern under the effect of fungicidal, fungistatic and subfungistatic doses . It was shown that within the first minutes of the contact any dose increased the volume and lowered the concentration of the dry matter of C . albicans cells due to impairment of the cytoplasmic membrane permeability . Later the fungicidal and fungistatic doses of amphotericin B induced irreversible pathological changes in the cells accompanied by an increase in the volume and a decrease in the mass and concentration of the dry matter in the cytoplasm . The subinhibitory concentrations of the drug promoted the fungus growth instead of its inhibition. J Clin Microbiol, 1983 Oct, 18(4), 849 - 57 Analysis of Candida albicans phenotypes from different geographical and anatomical sources; Odds FC et al.; Strain phenotypes of 330 Candida albicans isolates from five areas in the United States were determined on the basis of nine biochemical tests . Statistical analysis of the distribution of phenotypes revealed no significant differences among types from different anatomical sources . However, there were some differences among the phenotypes of strains from the different geographical areas, and there were substantial differences in biochemical phenotypes associated with strains susceptible and resistant to 5-fluorocytosine and between strains of serotypes A and B . Geographical differences in phenotypes of C . albicans were also noted between the 330 U.S . isolates and 247 isolates from Britain . Cluster analysis of the U.S . strains alone and of all of the U.S . and U.K . strains showed that C . albicans phenotypes can be grouped into fewer than 20 clusters with common biochemical properties. Biull Eksp Biol Med, 1983 Oct, 96(10), 80 - 2 {Interstrain differences in mice in developing migration inhibition factors to Candida albicans antigens}; Vorob'ev KV et al.; The authors studied the time course of MIF production by lymphocytes of CBA (H-2k), C57BL/6J (H-2b) and (CBA X C57BL/6J) F1 (H-2b/H-2k) mice sensitized to Candida albicans antigens . The interstrain differences in lymphokin production were identified, CBA mice appeared to be highly responsive, whereas C57BL/6J to be low-responsive . Partial hybridological analysis made it possible to ascertain the presence of the dominant type heredity of high MIF production in response to Candida albicans antigens. Lab Invest, 1983 Oct, 49(4), 460 - 7 Host-parasite interactions in the pathogenesis of experimental renal candidiasis; Barnes JL et al.; To study the pathogenesis of renal candidiasis, viable Candida albicans blastospores were injected directly into the left renal artery of New Zealand white rabbits . The progression of the disease was followed by light and electron microscopy over a 6-day period . Within 5 minutes after injection of the yeasts, the organisms localized within glomerular and peritubular capillaries of the cortex . Localization of yeasts within the capillaries occurred through adherence, demonstrated by the presence of surface fibrils originating from the yeast cells . Two to 10 hours later, inflammatory nodules comprised of polymorphonuclear leukocytes formed within capillary lumina . Many of the entrapped yeasts remained viable and extended through adjacent endothelium and epithelium by the formation of germ tubes which penetrated between or directly through intact host cells . After 24 hours, numerous hyphal forms were observed within tubules of the cortex, and some necrotic host cells were noted at sites of penetration . Abscesses replaced renal parenchyma in focal areas during subsequent time intervals . These studies indicate that attachment of Candida albicans to endothelium within capillaries of the cortex is a key event in the disease process . Also, growth of germ tubes into renal tubules provides a temporal advantage for amplification of Candida organisms. J Med Chem, 1983 Oct, 26(10), 1518 - 22 Design of anticandidal agents: synthesis and biological properties of analogues of polyoxin L; Shenbagamurthi P et al.; Six analogues of polyoxin L were synthesized from uridine . All of these analogues inhibited chitin synthetase from Candida albicans . Derivatization of the amine terminus of the polyoxin analogues resulted in loss of activity, and analogues containing aromatic amino acid residues were the most efficient inhibitors of chitin synthetase . The concentration of tryptophanyl uracil polyoxin C, 8, which caused 50% inhibition of chitin synthetase activity, was 1.6 X 10(-6) M . This was virtually identical with the activity found for polyoxin D . None of the inhibitors effectively competed with the entry of (Met)3 into C . albicans . All of the analogues caused severe morphological distortions of the yeast in culture, and a number of analogues killed C . albicans at millimolar concentrations . The results suggest that chitin synthetase inhibitors may have potential as anticandidal drugs. Infect Immun, 1983 Oct, 42(1), 285 - 92 Effect of strain of Staphylococcus aureus on synergism with Candida albicans resulting in mouse mortality and morbidity; Carlson E; Nine Staphylococcus aureus strains isolated from patients with toxic shock syndrome (TSS), two strains from non-disease-associated sources, and four strains from disease (not TSS)-associated sources were characterized for the intraperitoneal dose necessary to kill 50% of exposed animals (LD50) and toxic shock toxin production and studied for synergistic effects on mouse mortality and morbidity when combined with a sublethal dose of Candida albicans and inoculated intraperitoneally . Representative toxic shock toxin-producing strains (free of other enterotoxins) exhibited the following unique set of characteristics when inoculated intraperitoneally into mice and compared with all other strains tested: (i) lowest virulence when inoculated alone into mice as determined by the LD50; (ii) greatest synergistic decrease in LD50 (up to 70,000-fold as compared to up to 200-fold for other strains) when combined with C . albicans and injected intraperitoneally; and (iii) induced a characteristic, dose-independent, temporal death pattern in dually injected animals . When sublethal dual doses were used, animals receiving disease (TSS and not TSS)-associated S . aureus in combination with C . albicans developed symptoms, but some differences in symptomatologies, depending on the strain, were observed . The symptoms included conjunctivitis; gastrointestinal, neurological, and circulatory abnormalities; rash followed by desquamation; and patchy baldness . Although overlap in symptoms between animal treatment groups was observed, certain symptoms (neurological sequeae and petechial hemorrhages) were observed only in animals inoculated with a specific S . aureus strain combined with C . albicans . Animals receiving sublethal dual doses, which included non-disease-associated S . aureus, did not develop symptoms . When Staphylococcus epidermidis was combined with C . albicans and inoculated into mice, no synergistic effects on morbidity or mortality were observed. Infect Immun, 1983 Oct, 42(1), 1 - 9 Natural cell-mediated cytotoxicity against Candida albicans induced by cyclophosphamide: nature of the in vitro cytotoxic effector; Baccarini M et al.; We have recently reported the in vivo modulation of resistance to experimental Candida albicans infection by cyclophosphamide (150 mg/kg intraperitoneally) in mice and have shown that increased resistance to the microbial challenge occurs 12 to 21 days after treatment with the drug (Bistoni et al., Infect . Immun . 40: 46-55, 1983) . The event is accompanied by the appearance of a highly candidacidal cell population in the spleen and the activation of a subpopulation of natural cytotoxic effectors reactive in vitro against YAC-1 tumor cells . We now provide evidence that these anti-YAC-1 cytotoxic effectors are clearly distinct from the cyclophosphamide-induced candidacidal effectors, which seem to belong to a macrophage-monocyte lineage . The enhanced cytotoxic activity induced by cyclophosphamide was not restricted to C . albicans but was also exerted against a panel of Candida strains. J Antimicrob Chemother, 1983 Oct, 12(4), 303 - 16 Effect of imidazole antifungals on the development of germ tubes by strains of Candida albicans; Johnson EM et al.; Three imidazole antifungals (ketoconazole, tioconazole and miconazole) were examined for their effect on germ tube development by synchronous blastospore populations and on actively growing germ tubes of three strains of Candida albicans . After incubation in serum for 4 h the largest differences in germ tube elongation between strains were detected at concentrations (0.005 mg/l) where minimal inhibition was observed . Germ tube elongation in antifungal-containing serum diminished with increasing concentration . Maximum inhibition occurred at concentrations of 0.5 mg/l . All three antifungals inhibited the rate of hyphal elongation by the strains over a 6 h period at this concentration . Tests where germinated blastospores of strain 3281 were transferred to serum containing 0.5 mg/l of antifungal indicated that all three drugs inhibited further elongation . However, the rate of inhibition was dependent upon the length of time germination had proceeded in serum alone prior to transfer to antifungal-containing serum. Eur J Clin Microbiol, 1983 Oct, 2(5), 509 - 15 Once-daily administration of ceftriaxone in the treatment of meningitis and other serious infections in children; Martin E; Forty-three children (ten neonates, 15 infants and 18 older children) were treated with single daily doses of ceftriaxone (50 to 100 mg/kg) intravenously or intramuscularly for serious bacterial infections . The infections included meningitis (31 patients), brain abscesses (four patients), septicaemia (three patients), pleuro-pneumonia (two patients), septic arthritis and soft tissue phlegmona (three patients) . No other antibacterial agents were used except in four patients with brain abscesses, in whom ceftriaxone was combined with ornidazole . The overall bacteriological cure rate was 98%, and sterilisation of the cerebrospinal fluid occurred in 27 of 28 patients (96%) with proven bacterial meningitis . Two patients died, three survived with severe neurological sequelae; one neonate required partial gut resection . A complete clinical cure was achieved in the remaining 37 patients . Only one treatment failure was directly related to the drug therapy . The only side effect noted were sterilisation of the gut with overgrowth of Candida albicans in 35% of neonates and infants, an prolonged fever in 13% of all patients . Ceftriaxone given in a 24-hourly regimen is convenient and highly effective in serious bacterial infections in children and is without significant toxicity. Eur J Clin Microbiol, 1983 Oct, 2(5), 445 - 52 Effects of subinhibitory concentrations of ketoconazole on in vitro adherence of Candida albicans to vaginal epithelial cells; Sobel JD et al.; The in vitro adherence of multiple 14C-glucose labeled isolates of Candida albicans to exfoliated vaginal epithelial cells in the presence of subinhibitory concentrations of ketoconazole was studied with a new method utilizing differential centrifugation in a gelatin-PBS solution as well as by the standard method of direct microscopy measurement . Pre-incubation of stationary-phase candida in ketoconazole at concentrations of 0.002 to 0.1 microgram/ml for 4 h at 37 degrees C had no effect on adherence . The addition of ketoconazole to logarithmic phase Candida albicans failed to reduce the total number of cell-associated adherent yeast but exposure to subinhibitory concentrations of ketoconazole was associated with a dystrophic morphology of the blastospores, extensive clumping and reduced germination resulting in fewer individual candida blastospores directly attached to the cell membranes . Germination inhibition and a marked reduction in adherent candida was observed when 0.01 microgram/ml ketoconazole was added to Candida albicans incubated in germination promoting medium . The diminished adherence of Candida albicans to vaginal epithelial cells after exposure to subinhibitory concentrations of ketoconazole may have clinical relevance in preventing recurrent candida vaginitis. Infect Immun, 1983 Oct, 42(1), 76 - 80 Candidacidal activity of myeloperoxidase: mechanisms of inhibitory influence of soluble cell wall mannan; Wright CD et al.; We have previously demonstrated the ability of human neutrophil myeloperoxidase to bind to mannan isolated from Candida albicans . Mannan may therefore be a primary component of the yeast cell wall which provides for binding of myeloperoxidase, a requirement potentially important for the candidacidal activity of the enzyme . In this report, we describe experiments to consider the relationship of the mannan-binding activity of myeloperoxidase to its candidacidal activity and the possibility that free mannan may inhibit myeloperoxidase-mediated candidacidal activity . We observed that binding of myeloperoxidase to the target yeasts was required for killing of C . albicans . We also observed that addition of soluble mannan significantly reduced myeloperoxidase-mediated killing of the yeasts in a dose-dependent manner by antagonizing binding of myeloperoxidase . Soluble mannan was demonstrated to have a similar dose-dependent inhibitory effect on neutrophil-mediated candidacidal activity without influencing phagocytosis of the organism . On the basis of these observations, we speculate that mannan solubilized in plasma and tissue fluid may interfere with neutrophil-mediated host defense against Candida infection. Biochem Biophys Res Commun, 1983 Sep 30, 115(3), 1108 - 13 Mechanism of action of the antibiotic thiolactomycin inhibition of fatty acid synthesis of Escherichia coli; Hayashi T et al.; Thiolactomycin, an antibiotic with the structure of (4S)-(2E,5E)-2,4,6-trimethyl-3-hydroxy-2,5,7-octatriene-4-thiolide, inhibits the incorporation of {14C}acetate into cellular fatty acids of Escherichia coli . This antibiotic inhibits the fatty acid synthetase system of E . coli . However, the fatty acid synthetases from Saccharomyces cerevisiae, Candida albicans and rat liver are insensitive to thiolactomycin . This effect may account for the antibacterial activity of thiolactomycin and for its low toxicity in animals. J Immunol Methods, 1983 Sep 30, 63(1), 139 - 43 Comparison of three tests for measuring footpad swelling in the mouse; Ponton J et al.; Three tests, footpad thickness, footpad weight and footpad dye accumulation have been compared for measuring the local inflammatory reaction developed in the hind footpads of the mouse after injection of increasing doses of heat killed Candida albicans yeasts . The 3 tests showed high correlation indicating that any one of them may be used to evaluate such inflammatory reactions. Br Med J (Clin Res Ed), 1983 Sep 24, 287(6396), 861 - 2 Disseminated candidiasis: evidence of a distinctive syndrome in heroin abusers; Collignon PJ et al.; Seven young men developed similar manifestations of disseminated candidiasis after a single episode of intravenous heroin abuse . Sequential development of lesions of the eye, skin, and bone or costal cartilage was noted within 10 days after injection . Skin lesions were confined to the scalp and other hair bearing areas . Candida albicans was cultured readily from affected skin and costal cartilage . Histological examination of scalp biopsy specimens showed infiltration of hair follicles with chronic inflammatory cells and C albicans . Pseudohyphas of C albicans were also identified in and around hair shafts . The skin, skeletal, and small eye lesions resolved on systemic treatment with 1 g amphotericin B plus flucytosine . Pars plana vitrectomy plus local instillation of amphotericin B cured progressive chorioretinitis . These features may represent a distinctive syndrome of disseminated candidiasis in heroin abusers . Systemic antifungal treatment is curative in most cases. Minerva Med, 1983 Sep 15, 74(35), 2029 - 32 {Bacteriological and clinical notes on otitis externa in saturation . Double-blind study on the efficacy of prophylactic and therapeutic preparations}; Marroni A et al.; Microbiological analysis of the variation in the bacterial flora of the external auditory canal was carried out during 39 immersion in saturated solutions . A double blind test on the usefulness of prophylactic and therapeutic preparations was also carried out . Prophylactics . - 5% Al acetate in H2O (P1), Boric alcohol (P2), lactic acid in H2O (P3, Domeboro (P4), no prophylactic (P0) . After the immersions, a significant increase in Pseudomonas Aeruginosa and Candida Albicans (p less than 0,01) was noted in the auricular bacterial flora . Gram positive bacteria in general were considerably reduced (p less than 0,01) . Gram negative bacteria other than pseudomonas . A (p less than 0,3) and coagulase negative straphylococci (p less than 0,03) did not vary significantly . Prophylactic preparations P1 and P2 were shown to be significantly more effective than P3, P4 and P0 in preventing the symptomatology (p less than 0,01) . The most effective therapeutic preparation was found to be a locally applied gentamycinpolymixin association. Lancet, 1983 Sep 10, 2(8350), 599 - 602 Experimental transmission of macaque AIDS by means of inoculation of macaque lymphoma tissue; Letvin NL et al.; Acquired immuno-deficiency syndrome (AIDS) of macaques, an animal model for human AIDS, was transmitted to previously healthy macaque monkeys by means of inoculation of either tissue or a cell-free filtrate of a macaque lymphoma . The recipients showed evidence of profound lymphocyte dysfunction or died with infections from such opportunistic agents as Candida albicans, Cryptosporidium, and cytomegalovirus. J Infect, 1983 Sep, 7(2), 159 - 61 Fatal candida pneumonia in a non-immunosuppressed host; Worthington M; An 83-year-old previously well non-immunosuppressed woman developed invasive fatal candida pneumonia, apparently caused by aspiration . Diagnosis was suggested by the presence of sheets of budding yeasts and pseudohyphae on Gram-stained expectorated sputum and confirmed by an open lung biopsy which demonstrated candida invading lung tissue . Culture of material obtained by open lung biopsy yielded Candida albicans . At autopsy the patient had extensively invasive bilateral candida pneumonia . No other pathogens were isolated from sputum, open lung biopsy or at the time of autopsy . Evidence of disseminated candidiasis was not seen at autopsy . To our knowledge, this is only the fourth documented case of aspiration candida pneumonia in a non-immunosuppressed adult . While candida pneumonia in an immunocompetent adult is very rare, it should be considered in an elderly patient who is not responding to antibiotic therapy . Diagnosis requires aspiration or biopsy of lung, with preferably both histological and cultural evidence of candida infection. Farmaco {Sci}, 1983 Sep, 38(9), 709 - 12 {Aryl esters of N-benzyldithiocarbamic acid with antimycotic activity}; Mazza M et al.; Some aryl esters of N-benzyldithiocarbamic acid {substances (I leads to XVI)}, in which S aryl substituents were hydrophylic or potentially hydrophylic groups, were tested for in vitro antifungal activity against the following strains: Candida albicans, Saccharomyces cerevisiae and Trichophyton mentagrophytes . The substances were prepared by condensation of benzylisothiocyanate with suitable benzenethiols . The results, given in Table I, show the marked activity as antifungal agents of the N-benzyldithiocarbamic acid aryl esters studied; the antifungal activity, connected with the N-benzyldithiocarbamic group, is only slightly influenced by the nature of the substituents. J Antibiot (Tokyo), 1983 Sep, 36(9), 1195 - 200 Preparation, properties and biological activity of natural and semisynthetic urethanes of monensin; Westley JW et al.; Conversion of the monovalent polyether antibiotic monensin into a series of urethane derivatives substituted at C-26 causes a ten-fold increase in the cation transporting properties of the antibiotic as well as making the resulting semisynthetic urethanes divalent ionophores . These changes must in part account for the enhanced antimicrobial activities of the urethanes . The most active derivatives are the phenylurethanes which are ten times more active in vitro against Gram-positive bacteria and unlike monensin are active against Candida albicans and Penicillium digitatum . Another novel activity exhibited by four of the urethanes was against Plasmodium berghei, the causative agent for malaria. Clin Pharm, 1983 Sep-Oct, 2(5), 432 - 5 Delayed cutaneous hypersensitivity response in patients receiving nutritional support; Griffin RE et al.; The sensitivity and specificity of skin-test antigens were assessed, and the prevalence of anergy was determined in a group of hospitalized patients receiving aggressive nutritional therapy . All patients referred to a nutritional support service during a nine-month period were assessed for intact cellular immunity using Candida albicans, mumps, streptokinase/streptodornase, and tetanus toxoid skin tests for delayed cutaneous hypersensitivity . Some patients were retested at two-week intervals while they were receiving nutritional support . A total of 195 patients (97 men) ranging from 15 to 92 years old were tested; 68 patients received repeat skin tests . Of the 195 patients, 181 (92.8%) reacted positively to one or more antigens when tested initially; all patients (including anergic ones) who were retested reacted positively . Candida and mumps tests produced the highest percentages of positive responses (80 and 75%, respectively); the use of these two antigens concurrently produced a 92.3% response rate . Nonresponding patients to a nonresponding antigen converted to responders to that antigen upon second testing more frequently than responders converted to nonresponders . Candida and mumps skin tests detected anergy and demonstrated that immune responses were maintained and often restored by aggressive nutritional support. Nippon Geka Gakkai Zasshi, 1983 Sep, 84(9), 882 - 5 {Fungal sepsis and DIC in surgical patients}; Kambayashi J et al.; Of 53 surgical cases complicated with severe infection who were admitted to The Second Department of Surgery of Osaka University Hospital between 1975 and 1982, 9 cases were suffered from sepsis with positive blood culture for Candida albicans . All cases developed DIC and subsequent multiple organ failures (MOF), which was likely triggered by fungal sepsis because of the absence of any coexisting pathogens . Fungal sepsis was developed following a long term massive antimicrobial therapy in 7 cases and also following a long term steroid therapy in 1 cases . No apparent portal of fungal entry was confirmed except 3 cases with a positive fungal culture for central venous catheter . Six cases were fatal without improvement of DIC or MOF, to whom no early administration of antifungal agents was performed due to lack of recognition of fungal virulence . However, 3 cases were completely recovered from DIC and MOF by treatment with antifungal agents and anticoagulants . These observations suggest that DIC due to fungal sepsis may be eradicated by recognition of fungal virulence and by appropriate treatment with antifungal agents and anticoagulants. Ann Microbiol (Paris), 1983 Sep-Oct, 134B(2), 293 - 306 In vitro and in vivo adherence of Candida albicans to mucosal surfaces; Lehrer N et al.; In continuation of a previous study, chitin soluble extract (CSE) and anti-Candida albicans antibodies were found to inhibit the in vitro adherence of C . albicans to human vaginal epithelial cells by 60-70% . Pretreatment of epithelial cells with chitin, CSE or N-acetyl-glucosamine (NAG) decreased the percentage of adherence, while pretreatment of yeasts had no such effect, indicating that chitin or its derivatives may be involved in mediating the adherence of C . albicans . In vivo attachment of C . albicans to epithelial cells was studied in an experimental murine vaginitis created by inoculating mice intravaginally with yeasts at the oestrus stage . Attachment of the yeasts to exfoliated vaginal epithelial cells was followed microscopically, and the course of infection was assessed histopathologically in tissue sections at various times post-yeast inoculation . The infection rate at 24-h post-yeast inoculation was approximately 50% . Attempts were made to block in vivo attachment and prevent infection by pretreating 208 mice with either CSE, NAG, mannan or phosphate-buffered saline (PBS) prior to inoculation with yeasts . The infection rate among mice pretreated with mannan or PBS was 41.6% and 43.8%, respectively . Among CSE- or NAG-pretreated animals, the rate ranged from 0-9% . Treatment of mice with CSE or NAG after inoculation of the yeasts did not prevent infection . The data from the in vivo experiments reveal that pretreatment of animals with chitin derivatives blocks attachment of yeasts to the vaginal mucosal surfaces and leads to the prevention of vaginal infection in an experimental model. J Biochem (Tokyo), 1983 Sep, 94(3), 777 - 83 Isolation and purification of morphogenic autoregulatory substance produced by Candida albicans; Hazen KC et al.; The human pathogenic, dimorphic fungus Candida albicans produces in vitro a factor designated morphogenic autoregulatory substance (MARS) which suppresses yeast to mycelial transition . MARS is best produced when a high concentration of yeast cells (2 X 10(8)/ml) in a chemically defined medium is incubated at 37 degrees C for 9-15 h . MARS was isolated to apparent homogeneity by the following successive steps: charcoal absorption; pyridine elution; ether extraction; high pressure liquid chromatography, and Sephadex LH-20 chromatography . A 469-f