Candida albicans

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-fold increase in purity was obtained by these procedures . The use of purified MARS to study C . albicans yeast to mycelial transition may lead to a better understanding of morphogeneis of this important opportunistic pathogen.

Antimicrob Agents Chemother, 1983 Sep, 24(3), 401 - 8
Inhibitory effect of cerulenin and sodium butyrate on germination of Candida albicans; Hoberg KA et al.; Candida albicans germination in liquid medium was inhibition by the antilipogenic agent cerulenin and the fatty acid sodium butyrate . Although these inhibitors prevented germ tube emergence at concentrations of 1 microgram/ml and 20 mM, respectively, neither significantly affected cell viability as judged by trypan blue staining or the rate of protein biosynthesis throughout the time course of the experiments . Cerulenin treatment resulted in inhibition of lipid biosynthesis, but lipid biosynthetic capabilities remained unaltered in sodium butyrate-supplemented cultures . Because each inhibitor blocks germination by different mechanisms, their utility in distinguishing events directly correlated to germination was examined . In this context, chitin synthase activity was inhibited by both compounds, confirming the importance of chitin biosynthesis in C . albicans germination.

Sabouraudia, 1983 Sep, 21(3), 251 - 4
Scanning electron microscope study of Candida albicans invasion of cultured human cervical epithelial cells; Farrell SM et al.; The invasion of monolayer cultures of epithelial cells from the human uterine cervix by clinical isolates of Candida albicans was observed . Blastospores settle on the epithelial cells and produce germ tubes within 2 h . Hyphae penetrate the epithelial cell walls and destroy the cells, weaving in and out of the cytoplasm . No phagocytosis of yeast cells by epithelial cells was seen.

Sabouraudia, 1983 Sep, 21(3), 223 - 31
IgA and IgG serum antibodies to Candida albicans in women of child-bearing age; Schonheyder H et al.; IgA and IgG antibodies against Candida albicans culture filtrate were determined by enzyme-linked immunosorbent assay (ELISA) in sera from 84 pregnant and 21 non-pregnant women . IgA Candida antibody levels were found not to change significantly with age, whereas IgG Candida antibody levels were significantly higher in women aged 27 to 35 years than in women less than 24 years of age . Neither IgA nor IgG Candida antibody levels were related to the number of pregnancies . In a subgroup of 45 pregnant women examined for yeasts in the oral, anal and vaginal flora IgA Candida antibody levels were significantly higher in 13 women with negative cultures than in 19 women with recovery of C . albicans on plates . Intermediate levels of IgA Candida antibodies were found in 9 women with negative plate cultures, but positive enrichment broth cultures of C . albicans . All of 15 women with IgA ELISA values less than or equal to 0.51 had yeast-positive cultures compared with 17 of 30 women with IgA ELISA values greater than 0.51 . This may suggest a role of IgA antibodies in the clearance of C . albicans from mucosal surfaces in healthy individuals.

Sabouraudia, 1983 Sep, 21(3), 185 - 94
Immunological and pathological observations with Candida albicans-infected animals; Kuttin ES et al.; Mice and rabbits immunized intraperitoneally or intradermally with an ethanol-killed crude Candida albicans antigen and non-immunized controls were infected intravenously with C . albicans . The mortality rates clearly demonstrated immune protection, although the proportion of dead cells in the Candida immunization dose was inversely related to the degree of protection . Histopathological observations demonstrated distinct differences in the morphology of the fungal cells as well as in the host tissue reaction between the immunized and the non-immunized animals.

Sabouraudia, 1983 Sep, 21(3), 173 - 8
Interactions of serotypes A and B of Candida albicans in mice; Auger P et al.; Candida albicans serotypes A and B were mixed in different proportions and administered orally to white mice receiving a protein-free diet . Recoveries of the serotype from the stomach and rectosigmoid showed that the relative proportion of serotype A was consistently higher than in the inoculating suspension . No modification of serotype was observed in mice given only one serotype, and there was no change in proportions of serotypes coincubated in vitro . These observations indicate that host factors must be involved in selective colonization by the serotypes in vivo.

J Gen Microbiol, 1983 Sep, 129 (Pt 9), 2809 - 24
Growth and the inducibility of mycelium formation in Candida albicans: a single-cell analysis using a perfusion chamber; Soll DR et al.; In Candida albicans, cells actively growing in the budding form cannot be immediately induced to form a mycelium until they enter stationary phase . However, if exponential phase cells are starved for a minimum of 10 to 20 min, they are inducible . Using a video-monitored perfusion chamber, we found that starved cells were able to form mycelia regardless of their position in the budding cycle . When starved exponential cells were released into fresh nutrient medium at high temperature and pH, conditions conducive to mycelium formation, unbudded cells evaginated after an average lag period of 75 min and then grew exclusively in the mycelial form . Depending upon the volume, or maturity, of the bud, budded cells entered two different avenues of outgrowth leading to mycelium formation . If the daughter bud was small, growth resumed by apical elongation of the bud, leading to a 'shmoo' shape which tapered into an apical mycelium . If the daughter bud was large, the cell underwent a sequence of evaginations: first, the mother cell evaginated after an average period of 75 min; then the daughter bud evaginated 40 min later . Both evaginations then grew in the mycelial form . In this latter sequence, the evagination on the mother cell was positioned non-randomly, occurring in the majority of cells adjacent to the bud . All buds undergoing evagination contained a nucleus, but roughly 20% of buds undergoing apical elongation did not.

Ann Intern Med, 1983 Sep, 99(3), 334 - 6
Fungal peritonitis in patients on continuous ambulatory peritoneal dialysis; Kerr CM et al.; Fungal peritonitis is a rare complication in patients on continuous ambulatory peritoneal dialysis . We report five recent cases and their management . The fungi isolated were Candida albicans, C . parapsilosis, Exophiala jeanselmei, Drechslera spicifera, and a Fusarium species . Chemotherapy was attempted with various regimens including oral ketoconazole, intravenous or intraperitoneal amphotericin B, and oral flucytosine . Pharmacokinetic studies were done in two patients receiving treatment with one of these drugs . Three patients were cured of their fungal infection . Three patients whose Tenckhoff catheters were left in situ died, whereas two patients whose catheters were removed survived . Our experience suggests that removal of the peritoneal catheter should be considered once the diagnosis of fungal peritonitis is established.

Infect Immun, 1983 Sep, 41(3), 1024 - 30
Characterization of Candida albicans adherence to human vaginal epithelial cells in vitro; Lee JC et al.; Certain environmental, physical, and biochemical aspects of Candida albicans adherence to human vaginal epithelial cells were characterized by using an in vitro radiometric adherence assay . Blastospores harvested from cultures grown at 25 degrees C adhered to vaginal epithelial cells in significantly greater numbers than did blastospores isolated from cultures grown at 37 degrees C . C . albicans viability was not essential for adherence, but severe methods used to kill the blastospores did reduce their attachment . The addition of sodium chloride, divalent cations, sugars, mannan, or mannoprotein to the assay had no effect on attachment . Pretreatment of the blastospores with detergents, salts, urea, glycosidases, lipase, or pepsin did not affect adherence, but treatment with reducing agents or five proteolytic enzymes did render C . albicans nonadherent . Cell wall fragments prepared from C . albicans, but not from Candida krusei, adhered to vaginal epithelial cells . Loss of adherence after the cell walls were treated with alpha-mannosidase or papain suggests that cell wall mannoprotein is an essential component of the C . albicans adhesin.

Gastroenterology, 1983 Sep, 85(3), 535 - 7
Occurrence of Candida in gastric ulcers . Significance for the healing process; Gotlieb-Jensen K et al.; In 42 consecutive adult patients with benign gastric ulcers, endoscopic biopsy specimens were examined histologically for infiltration with Candida albicans before the patients entered a double-blind trial of either cimetidine or placebo . Fifteen cases of candidal infiltration were found, giving an overall incidence of 36% . Repeated endoscopy after 6 wk showed complete ulcer healing in 9 of 15 patients with Candida-infiltrated ulcers, compared with 20 of 27 patients with no infiltration . It is concluded that the occurrence of Candida in benign gastric ulcers has no influence on the healing process.

Infect Immun, 1983 Sep, 41(3), 902 - 7
Systemic candidosis in silica-treated athymic and euthymic mice; Lee KW et al.; Intravenous silica injections were used to assess the role of macrophages in the resistance of BALB/c nude and euthymic mice to systemic candidosis . CFU of Candida albicans in the kidneys, livers, and spleens of saline- or silica-treated mice were enumerated at various times after inoculation with 10(4) viable yeast cells . The number of C . albicans organisms recovered from the kidneys of silica-treated euthymic mice was similar to the number recovered from saline-treated controls during the first 3 days of infection; however, at every assay period thereafter, the number of organisms recovered from the kidneys of silica-treated mice was dramatically reduced (100- to 1,000-fold) . Conversely, silica-treated nude mice were no more susceptible to systemic candidosis than were saline-injected nude mice . Silica treatment did not alter the ability of treated or control mice to clear C . albicans from the liver and spleen . These results demonstrate that macrophages play an important role in susceptibility to Candida infections.

Blood, 1983 Sep, 62(3), 635 - 44
Inhibition of zymosan activation of human neutrophil oxidative metabolism by a mouse monoclonal antibody; Nauseef WM et al.; We have studied a neutrophil-specific murine monoclonal antibody, PMN7C3 (IgG3), which specifically alters PMN oxidative metabolism stimulated by serum-opsonized zymosan (STZ) or Candida albicans (STC) . Polymorphonuclear cells (PMNs) exposed to PMN7C3 show a significant depression in O2- release (52.8% +/- 2.5% of control), H2O2 release (44.4% +/- 6.0% of control), and O2 consumption (73.9% +/- 2.6% of control) in response to STZ . O2 release in response to phorbol myristate acetate (PMA) was modestly reduced (78.4% +/- 3.7%) by PMN7C3 treatment, but not to the extent seen with STZ or STC . PMN7C3 did not affect O2 release by PMNs stimulated by zymosan opsonized with IgG or by S . aureus, A 23187, or FMLP . PMN7C3 was not cytotoxic, did not trigger oxidative metabolism when used as a stimulus, did not alter STZ-induced degranulation, and did not interfere with binding or uptake of STZ by PMNs . Exposure of PMNs to PMN7C3 decreased PMN rosette formation with erythrocytes coated with C3b (54% of control) or C3bi (63% of control), but had no affect on rosette formation with IgG-coated erythrocytes . PMN7C3 does not bind to monocytes and had no affect on rosette formation by this cell type . Binding of antibody PMN7C3 to the neutrophil surface inhibits the oxidative response to opsonized STZ or STC, possibly in part by altering the function or expression of C3b and C3bi receptors . Monoclonal antibodies such as PMN7C3 provide highly specific probes that may be used to define the molecular features of the stimulus-coupled response of PMN activation.

Vet Rec, 1983 Aug 6, 113(6), 131 - 2
Mycotic invasion of the mare's uterus; Blue MG; Uterine infections in three mares following repeated uterine manipulations and antibiotic therapy were caused by Aspergillus fumigatus in two cases and Candida albicans in the third . Two of the infections were noticed during dioestrus and one at oestrus and one mare produced a purulent vulval discharge . Large numbers of neutrophils, increased protein concentrations and the presence of fungal hyphae in flushings from the uterine lumen were indicative of active infection . The mycotic infections caused only transient aberrations of the oestrous cycle and recovery without treatment was completed within 23 days.

Am J Med, 1983 Aug, 75(2), 295 - 304
Genetic deficiency of C4 presenting with recurrent infections and a SLE-like disease . Genetic and immunologic studies; Mascart-Lemone F et al.; A young girl presenting with recurrent pulmonary infections and atypical lupus erythematosus was totally deficient in C4 . In one sister, also deficient in C4, the same symptoms developed . Results of family studies were consistent with an autosomal recessive mode of transmission and with linkage of the genes determining C4 deficiency to those of the major histocompatibility complex . The patient's serum and red cells were Chido- and Rodgers-negative . Humoral and cellular immunity were normal, except for a low lymphocyte response in mixed lymphocyte culture . The cellular function of the patient's polymorphonuclear leukocytes was normal, for both phagocytosis and bactericidal activity using Candida albicans . However, in the presence of C4-deficient serum, opsonin generation and bactericidal indexes were diminished . These defects were completely reversible upon addition of purified C4.

J Med Microbiol, 1983 Aug, 16(3), 363 - 9
The role of iron deficiency in experimentally-induced oral candidosis in the rat; Rennie JS et al.; In comparison with normal rats, those with iron deficiency anaemia showed no significant difference in susceptibility to experimental infection with Candida albicans although anaemic rats had a significantly greater incidence of persistent infection . These findings support the suggestion that patients with chronic candidosis should be investigated for iron deficiency.

Invest Ophthalmol Vis Sci, 1983 Aug, 24(8), 1098 - 102
Efficacy of antifungal agents in the cornea . I . A comparative study; O'Day DM et al.; A standardized model of Candida albicans keratitis was developed in pigmented rabbits using a quantitative mycologic technique to evaluate the disease at intervals throughout the course . In this model, using two different infecting strains, the efficacy of five antifungal agents was compared . Amphotericin B, in concentrations of 0.5% to 0.075%, was superior to all other agents tested . Natamycin 5% ranked next, followed by 1% flucytosine, and 1% miconazole . Ketoconazole 1% was ineffective.

Bull Soc Pathol Exot Filiales, 1983 Aug-Oct, 76(4), 351 - 6
{Study of yeast flora of medical interest on the beach of Saint Anne in Guadeloupe}; Boiron P et al.; An investigation of the yeast flora of medical interest was performed in sand and sea water of Sainte-Anne beach, in Guadeloupe . Yeast species of the genera: Candida, Torulopsis, Trichosporon, have been isolated, concurrently in those two environments; some of them were found in very close proportions . From this part, the authors consider the eventuality of a same source for these yeasts . The absence of Candida albicans corroborate the hypothesis in the preliminary study of the margin origin of the isolated yeasts.

Arch Microbiol, 1983 Aug, 135(2), 130 - 6
Growth inhibitory effect of antibiotic tetaine on yeast and mycelial forms of Candida albicans; Milewski S et al.; The mycelial (M) form of Candida albicans is more sensitive to the action of the antibiotic tetaine than the yeast (Y) form . Tetaine, at low concentrations about 1 microgram/ml also inhibits Y-M transition . It causes severe deformation of cells, agglutination and inhibits septum formation in the yeast forms . Tetaine action is reversed by dipeptides in both forms and by tripeptides in M form . N-acetyl glucosamine is a powerful antagonist of tetaine action on both morphological forms . Tetaine action on mycelial forms is slightly antagonised by N-acetyl mannosamine and very powerfully by glutamine.

Antimicrob Agents Chemother, 1983 Aug, 24(2), 181 - 5
Sodium hypochlorite decontamination of split-thickness cadaveric skin infected with bacteria and yeast with subsequent isolation and growth of basal cells to confluency in tissue culture; Fader RC et al.; The ability of sodium hypochlorite to decontaminate skin while leaving sufficient epidermal cell viability for growth in tissue culture was investigated with an in vitro system . Split-thickness cadaveric skin was infected with Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans and subsequently treated with various concentrations of sodium hypochlorite for various time intervals . Exposure to a 0.5% solution of sodium hypochlorite for 6 min effectively decontaminated the skin while leaving 66% of the basal cells viable . The basal cells were subsequently grown to confluency in tissue culture . This study demonstrates that microbial colonization of skin can be eliminated by exposure to dilute hypochlorite . This procedure, while decontaminating the skin, leaves sufficient viability of epidermal cells for subsequent growth and expansion in tissue culture, elements essential for grafting over wounds.

J Clin Microbiol, 1983 Aug, 18(2), 430 - 1
Preliminary investigation of Candida albicans biovars; Roman MC et al.; A total of 126 Candida albicans strains were enzymatically evaluated by the API ZYM system . Four enzymatically based groups of C . albicans are recognized.

J Natl Cancer Inst, 1983 Aug, 71(2), 299 - 307
Relationships among tumor load, route of tumor inoculation, and response to immunochemotherapy in a murine lymphoma model; Marconi P et al.; The combined effects of nonspecific immunostimulation with Candida albicans (CA) and chemotherapy were studied in (BALB/cCr X DBA/2Cr)F1 and (C57BL/6Cr X DBA/2Cr)F1 mice bearing virus-induced LSTRA lymphomas . Paradoxically, animals treated with a relatively high number of tumor cells responded better to therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) than those challenged with a low number of tumor cells . However, the majority of mice subjected to low initial tumor load were cured when they were treated with chemotherapy or chemotherapy plus booster injection of CA at a relatively "late" stage of the disease, i.e., when high tumor load was present in tumor-bearing hosts . It has been shown that this phenomenon, provisionally called high tumor load protection, occurs when the animals are challenged ip but not when they are challenged iv with the tumor and is abolished by total-body gamma-irradiation . Moreover, marked host protection can be attained when immunostimulated mice, inoculated iv with lymphoma cells, are subjected to simultaneous challenge with high inocula of the same tumor ip, followed by BCNU administration . These data stress the importance of the peritoneal cavity for successful CA plus drug treatment and suggest that optimal tumor "antigen load" should be present at the time of CA and/or BCNU administration.

J Gen Microbiol, 1983 Aug, 129 (Pt 8), 2367 - 78
The in situ assay of Candida albicans enzymes during yeast growth and germ-tube formation; Ram SP et al.; Conditions are described for the preparation of permeabilized cells of Candida albicans . This method has been used for the in situ assay of enzymes in both yeast cells and germ-tube forming cells . A mixture of toluene/ethanol/Triton X-100 (1:4:0.2, by vol.) at 15% (v/v) and 8% (v/v) was optimal for the in situ assay of glucose-6-phosphate dehydrogenase in yeast and germ-tube forming cells, respectively . The concentration of toluene/ethanol/Triton X-100 required for optimal in situ activity of other enzymes was influenced by the cellular location of the enzyme, growth phase and morphology . The membrane-bound enzymes (chitin synthase, glucan synthase, ATPase), cytosolic enzymes (glucose-6-phosphate dehydrogenase, isocitrate dehydrogenase, pyruvate kinase, phosphofructokinase, alkaline phosphatase, glucosamine-6-phosphate deaminase and N-acetylglucosamine kinase) and wall enzymes (beta-glucosidase and acid phosphatase) were measured and compared to the activity obtained in cell extracts . The pattern of enzyme induction and the properties of the allosteric enzymes phosphofructokinase and pyruvate kinase were measured in situ . Pyruvate kinase in situ was homotropic for phosphoenolpyruvate with a Hill coefficient of 1.9 and a S0.5 of 0.6 mM, whereas in cell extracts, it had a Hill coefficient of 1.9 and a S0.5 of 1.0 mM . The Km for ATP was 1.6 mM in cell extracts and 1.8 mM in permeabilized cells . In situ phosphofructokinase was homotropic for fructose 6-phosphate (S0.5 of 2.3 mM, Hill coefficient of 4.0) . The kinetic properties of pyruvate kinase and phosphofructokinase measured in situ or in vitro were similar for both yeast cells and germ-tube forming cells.

Dtsch Med Wochenschr, 1983 Jul 8, 108(27), 1062 - 5
{Candida meningitis . Case report}; Knuth A et al.; Subacute meningitis caused by Candida albicans was confirmed by culture and immunoserologically in a 19-year-old girl . Combined administration of amphotericin B and flucytosine only slowly affected the course of the disease despite impressive improvement in clinical symptoms . Pleocytosis (1000/mm3) in cerebrospinal fluid persisted . Falling Candida antibody titre in serum and CSF, however, pointed to an improvement in the acute infection . Treatment had to be discontinued after 42 days because of side-effects such as rigor, fever and polyuria with low concentration . Under serial clinical observations with occasional CSF punctures complete cure occurred with normal CSF findings . There was an additional and unusual neurological-otological condition of intermittent inner-ear deafness, left more than right, before treatment . Recording of early auditory evoked potentials pointed to an involvement of the cranial nerves as part of the inflammatory process.

Clin Exp Immunol, 1983 Jul, 53(1), 165 - 74
Circulating immune complexes in patients with Candida albicans infections; Burges G et al.; The existence of circulating immune complexes in patients with candidiasis has been suggested but not confirmed . In this study we have used four immune complex screening techniques (direct nephelometry, Clq binding assay, PEG-IgG assay and PEG-C4 assay) and an immune complex score compiled from results of the individual tests to establish that elevated levels of immune complexes do exist in a series of 11 patients with systemic candidiasis as compared with a group of 18 normal controls . Isolation and characterization of high molecular weight fractions from the sera of five patients with candidiasis and further purification by affinity chromatography on Sepharose 4B-protein A substantiated the presence of anti-Candida antibody and/or Candida antigen in at least three of them . The presence of complement components and IgG in these fractions further supported the existence of immune complexes containing microbial antigen and antibody.

Pediatr Med Chir, 1983 Jul-Aug, 5(4), 161 - 9
{Aerosol administration in antibiotic therapy of cystic fibrosis}; Battistini A et al.; The aim of this research was to evaluate the response to aerosol antibiotic therapy in Cystic Fibrosis (CF) patients, who because of severe lung disease, were obligated to frequent hospitalizations to undergo intravenous antibiotic therapy . Ten patients, aged 2 to 20 years were submitted to 4 months cycles of aerosol antibiotic therapy for a total of 18 cycles . The daily treatment consisted of carbenicillin 1 g b.d . and gentamicin 80 mgs b.d . At the end of treatment there was a statistically significant improvement of the modified Huang score and of single clinical parameters such as body growth, apetite, physical activity, clinical thoracic evaluation, appearance of sputum . Almost all of the radiographic items remained unchanged: in only 4 cases there was an improvement of the atelectasis-broncopneumonia type lesions . Regarding lung function, there was a statistically significant increase of maximum midexpiratory flow rate (MMEF) from 40% predicted before treatment to 50% predicted after . The reduction of residual volume (RV) from 270% predicted before 170% predicted after treatment was quantitatively more important . Furthermore, the treatment brought about a drastic reduction in number of hospitalizations: from an average of 1,7 hospitalizations/year before to an average of 0,3 hospitalizations/year during treatment . The increased number of isolations of isolations of candida albicans is the only report which favors possible adverse effects, in particular the possibility that this type of treatment favors lung mycosis.

J Cell Physiol, 1983 Jul, 116(1), 111 - 7
The study of human myeloid differentiation using bromodeoxyuridine (BrdU); Keoffler HP et al.; Little is known concerning the mechanism of myeloid differentiation . A human promyelocytic cell line (HL-60) differentiates to granulocytes or macrophage-like cells when cultured with a variety of agents . How these agents trigger myeloid differentiation is not understood . This study shows that 1.0-10.0 micrograms/ml bromodeoxyuridine (BrdU) induced myeloid differentiation of HL-60 in liquid culture . After 7 days, BrdU (3.0 micrograms/ml) produced only moderate inhibition of HL-60 growth, but induced myeloid maturation with 40% of the cells becoming morphologically more mature; 41% developed the ability to reduce nitroblue tetrazolium (NBT); 19% phagocytized Candida albicans; and 18% developed Fc receptors . The action of BrdU was mimicked by 5-iodo-deoxyuridine . Thymidine (Td) (1- to 10-fold excess) competitively inhibited incorporation of {3H}BrdU into DNA of HL-60 and inhibited the triggering of HL-60 differentiation by BrdU . The BrdU-induced maturation of HL-60 correlated with the incorporation of BrdU into DNA of HL-60 . DNA buoyant density studies showed that about 46% of the Td was replaced by BrdU in each DNA strand of HL-60 as the cells differentiated in culture containing 3 micrograms/ml BrdU for 7 days . We established 20 thymidine kinase (TK)-deficient HL-60 clones . The HL-60 TK-deficient cells were unable to phosphorylate Td, to incorporate either {3H}Td or {3H}BrdU or differentiate in the presence of BrdU (1-1000 micrograms/ml) . The HL-60 TK-deficient cells retained the ability to differentiate in the presence of other HL-60 inducers . Taken together, the studies suggest myeloid differentiation of HL-60 is triggered because of incorporation of BrdU into DNA of the cells.

Rev Infect Dis, 1983 Jul-Aug, 5 Suppl 3, S626 - 30
Combination antifungal chemotherapy for experimental disseminated candidiasis: lack of correlation between in vitro and in vivo observations with amphotericin B and rifampin; Ernst JD et al.; Disseminated candidiasis was established in guinea pigs immunosuppressed with high-dose cortisone acetate . After the disease had been characterized by histopathologic study and quantitative culture of selected organs, guinea pigs were given amphotericin B alone or in combination with rifampin . The addition of rifampin to the regimen enhanced the in vitro rate of killing of the strain of Candida albicans used in the studies but was not noticeably beneficial in treatment of the disease in guinea pigs . Thus, the demonstration of an enhanced rate of killing in vitro was not a reliable basis for prediction of the response to the drug in vivo.

Rev Infect Dis, 1983 Jul-Aug, 5 Suppl 3, S620 - 5
Interaction of rifampin with other antifungal agents in experimental murine candidiasis; Graybill JR et al.; A murine model of systemic candidiasis was used for evaluation of the interaction of rifampin with ketoconazole and amphotericin B . In vitro studies with a clinical isolate of Candida albicans showed that rifampin modestly potentiated the antifungal activity of both of these drugs . When mice were challenged iv with C . albicans, therapy with rifampin plus ketoconazole or rifampin plus amphotericin B significantly reduced counts in kidney tissue from levels in untreated controls . However, rifampin plus amphotericin B was no more effective than amphotericin B alone, and rifampin plus ketoconazole was no more effective than ketoconazole alone . In challenges with lethal numbers of organisms, amphotericin B or ketoconazole alone increased the rate of survival from 0% to approximately 50%, and the addition of rifampin to the regimen conferred no further benefit . Therefore, the use of rifampin with either of these antifungal agents resulted in minimal, if any, increase in efficacy.

Microbiologica, 1983 Jul, 6(3), 207 - 20
Suppression of Friend leukemia cell-induced tumours by cellular preparations of Candida albicans; Cassone A et al.; Inactivated cellular preparations and cell wall materials of Candida albicans (CA) were tested for their capacity to suppress the growth of Friend Leukemia Cell (FLC)-induced tumours and the infection by Friend Leukemia Virus (FLV) in histocompatible mice . Factors affecting the inhibition of tumor growth by CA cellular preparations were: i) the schedule of agent administration; ii) the method of cell inactivation; iii) the FLC load . In particular, mice given 10(7) yeast cells, inactivated by cold alkali, on days -14 and +1 with respect to 10(4) FLC challenge on day 0 did not develop tumors . A crude cell wall fraction derived from cells extracted with hot alkali was still effective in reducing (but not suppressing) tumour growth whereas a purified, particulate glucan fraction (glucan "ghosts", essentially consisting of beta 1,3-1,6 glucan) was ineffective . No cellular preparation or cell wall fraction exerted anti-FLV effects (as shown by splenomegaly measurements) nor did any CA material induce interferon-like activity in the serum of animals injected with either FLC or FLV . Therefore, the observed antitumor activity by CA was not mediated by antiviral effects but possibly due to an "adjuvant-type", nonspecific, immunopotentiation of host antitumor response, as documented in other animal tumor models.

J Gen Microbiol, 1983 Jul, 129 (Pt 7), 2327 - 30
Production of contiguously arranged chlamydospores in Candida albicans; Akisada T et al.; Contiguous arrangements of two to three chlamydospores occurred in a clinical isolate of Candida albicans . Time-lapse photography showed that the terminal cell of a cell chain was first transformed into a chlamydospore and such transformation proceeded centripetally to the next cell in the chain . Ultrathin sections revealed that the outermost layer of the three-layered chlamydospore wall was continuous throughout the interconnected spores, with the other layers surrounding each spore separately . Chlamydospore chains were common in this organism.

Monatsschr Kinderheilkd, 1983 Jul, 131(7), 441 - 7
{Nosocomial dyspepsia in newborn and young infants . A 15-month prospective study with continuous Rotavirus surveillance}; Forster J et al.; A 15 months prospective study of gastroenteritis in hospitalized newborns and infants (N = 201) was combined with a Rotavirus infection surveillance . Stool specimens were investigated weekly (CFT) . From patients with gastroenteritis (N = 320) an infectious agent could be detected on average in 41% of each patient group: Rotavirus N = 54, Staph . aureus N = 22, toxin producing E . coli N = 4, other bacteria N = 25, Candida albicans N = 17, Echovirus 11 N = 1 . With certain exceptions, the pathogens were distributed equally within the patient groups . However, Candida albicans appeared most frequently in premature children and the highest incidence of Rotavirus infections was observed in premature small for date babies . Rotavirus caused the mildest illness . The severest forms had usually no detectable cause . Bacteria took up an intermediate position . 68% of patients with detectable Rotavirus in the faeces had symptoms . However, treatment was required in only 25% of premature and small for date babies and 40% of normal newborns . In newborns and infants an isolated tachypnoea was observed 3 days prior to onset of a Rotavirus induced gastroenteritis . Breast fed infants showed no evidence of increased protection . Rotavirus antibodies were detectable in 58% of children prior to infection . The study presents evidence for the value of separate of patient care and meticulous hand disinfection, especially in the case of Rotavirus induced gastroenteritis.

Biomaterials, 1983 Jul, 4(3), 205 - 9
An in vitro and in vivo study of the effect of incorporation of chlorhexidine into autopolymerizing acrylic resin plates upon the growth of Candida albicans; Lamb DJ et al.; Chlorhexidine acetate was incorporated into autopolymerizing acrylic resin and, after studying its ability to diffuse out in vitro, an investigation was made into the potential of the mixture to treat palatal candidosis in the rat . Chlorhexidine was found to diffuse out of acrylic in fungicidal concentrations for up to three weeks when mixed with the acrylic powder in the proportion of 7.5% (w/w) . At this concentration it was found that palatal candidosis as produced by the technique of Shakir et al . was cured or prevented . However, rats fitted with chlorhexidine supplemented plates were found not to take sufficient food during the experimental period to maintain their body weight.

J Lab Clin Med, 1983 Jul, 102(1), 126 - 32
Activity of two polyene and two imidazole antimicrobics on Candida albicans in human fibrin clots; Smith BM et al.; The vegetations of infective fungal endocarditis were simulated by preparing human fibrin clots containing 10(5) CFU of Candida albicans per clot . Clots were incubated in human serum without drugs (controls) or with equimolar concentrations (2.5 to 20 nmol/ml) of four antifungal antimicrobics: AMB and miconazole (both colloidal suspensions) and DAB and KET (both molecularly dispersed) . Over a period of 4 days of incubation, clots were resuspended in freshly prepared serum-antimicrobic every 12 hr . Cohorts of control and drug-exposed clots were cultured quantitatively at 24 hr intervals . Neither imidazole at any concentration tested prevented growth of C . albicans to an extent that was significantly different from growth in the control clots . Both polyenes reduced the CFU/clot, with AMB significantly more active than DAB.

J Exp Med, 1983 Jul 1, 158(1), 174 - 91
Relative efficacy of human monocytes and dendritic cells as accessory cells for T cell replication; Van Voorhis WC et al.; Monocyte-specific monoclonal antibodies (7) were used to compare the efficacy of monocytes and dendritic cells as accessory or stimulator cells for human T cell replication . Both unfractionated and plastic-adherent mononuclear cells were first treated with a cytolytic antimonocyte antibody that kills greater than 95% of monocytes but not dendritic cells . When tested as stimulators of the mixed leukocyte reaction (MLR) and of oxidative mitogenesis (the proliferation of T cells modified with sodium periodate), the monocyte-depleted cells had normal or enhanced stimulatory capacity . Monocyte-depleted mononuclear cells also proliferated normally to soluble antigens (Candida albicans, tetanus toxoid), even under limiting conditions of cell dose, antigen dose, and culture time . Adherent blood mononuclear cells were next separated into monocyte-enriched and -depleted components using fluoresceinated antimonocyte antibody and the cell sorter . The depleted fraction (less than 2% monocytes by esterase staining and by cytology) contained the dendritic cells and exhibited at least 75% of the accessory activity . The monocyte-rich fraction (approximately 97% esterase positive) stimulated the MLR and oxidative mitogenesis weakly, and was comparable in potency to nonadherent cells . Cell-specific antibodies and complement were also used to prepare dendritic cells that were thoroughly depleted of monocytes and lymphocytes . The dendritic cells (70-80% pure) were potent stimulators of the allogeneic MLR, syngeneic MLR, and tetanus toxoid response, being active at stimulator to responder ratios of 1:100 or less . Taken together with previous studies (1, 2), these experiments indicate that the dendritic cell is the major stimulator of T cell replication in man . The contribution of class II products of the major histocompatibility complex (7) was then evaluated with a new monoclonal, 9.3F10 . Accessory function was dramatically inhibited if cells bearing class II antigens were killed with 9.3F10 and complement, or if class II molecules were blocked by the addition of 9.3F10 Fab to the culture medium . The expression of 9.3F10 class II products was therefore studied on purified monocytes and dendritic cells . Most if not all cells in both populations reacted with 9.3F10, and each population exhibited approximately 150,000 125I-Fab 9.3F10 binding sites per cell . Since Ia+ dendritic cells are active accessory cells, but Ia+ monocytes are not, class II products are necessary but not sufficient for the stimulation of T cell proliferation in man.

Infect Immun, 1983 Jul, 41(1), 33 - 8
Candida albicans-induced agglutinin and immunoglobulin E responses in mice; Winterrowd GE et al.; Mice varied in their ability to make detectable antibody responses to cell surface determinants of Candida albicans depending upon the antigen preparation and the immunization schedule used . Immunoglobulin M (IgM) appeared to be the major class of antibody responsible for the C . albicans-agglutinating activity of the immune sera . Various inbred strains of mice injected with a ribosomal fraction from C . albicans produced a low titer (average, 4 to 8) of yeast cell agglutinins and a higher titer (64 to 512) of IgE antibodies detected by passive cutaneous anaphylaxis (PCA) in rats . The two kinds of antibodies appeared to be specific for different antigens because the agglutinin, but not IgE, could be removed by absorbing the serum with a polysaccharide from the cell wall of C . albicans, but the polysaccharide did not provoke the PCA reaction . C . albicans-specific IgE antibodies showed cross-reactivity (PCA) with ribosomal antigens from a strain of C . albicans and C . tropicalis, but PCA reactions could not be elicited with similar antigen preparations from other yeast species . IgE responses were also detected in over 20% of the mice infected intravenously or intraperitoneally with live C . albicans.

J Immunol Methods, 1983 Jun 24, 61(1), 107 - 16
Detection of Candida proteinase by enzyme immunoassay and interaction of the enzyme with alpha-2-macroglobulin; Ruchel R et al.; Double antibody immunoassay of secretory aspartic proteinases from 2 strains of the yeast Candida albicans was performed in microtest plates with rabbit antibody and peroxidase conjugated rabbit antibody . The test detects approximately 0.1 ng of proteinase and is 2 orders of magnitude more sensitive than direct measurement of enzymic activity with hemoglobin as a substrate . The immunoassay was affected both by alkaline denaturation, which is a common feature of aspartic proteinases, and by the presence of the proteinase scavenger alpha-2-macroglobulin . Conditions are described that allow for comparison of proteinases from different strains of yeast and minimize the interference of macroglobulin.

Mycopathologia, 1983 Jun 20, 82(3), 167 - 73
Further evaluation of factors affecting a rapid ELISA procedure for detection of IgG antibodies to Candida albicans; Richardson MD et al.; A rapid enzyme-linked immunosorbent assay (ELISA) was developed to detect IgG antibodies against a cytoplasmic antigen of Candida albicans . The optimum conditions and time required for each step were investigated . Pre-equilibration at 37 degrees C and constant agitation of immunoreactants resulted in a total test time of 1 h for examination of single serum dilutions . Initial binding of the antigen at 37 degrees C to the solid phase occurred within 4-6 min and was dependent on concentration . A serum dilution of 100-fold resulted in adequate discrimination between precipitin test-positive and -negative sera . Interaction of antibody and the bound antigen was maximal after 6 min incubation at 37 degrees C and was dependent upon the precipitin titre of the serum . Ten minutes was selected as the optimal incubation time for each of the stages, by which time maximal binding had occurred, irrespective of antibody affinity for antigen . The ELISA was completed by incubation at 37 degrees C for 10 min with alkaline phosphatase-conjugated anti-human IgG . Discrimination between positive and negative test sera was achieved by incorporating in each test run precipitin test-positive and -negative reference sera from groups of persons with or without C . albicans colonization or infection . Closest agreement between sera positive for C . albicans precipitins by counter-immunoelectrophoresis and the rapid ELISA was seen when reference negative sera were selected from non-colonized individuals.

J Clin Microbiol, 1983 Jun, 17(6), 1166 - 9
Simultaneous determination of arabinitol and mannose by gas-liquid chromatography in experimental candidiasis; de Repentigny L et al.; A method is described for the simultaneous quantitation of D-arabinitol and D-mannose in serum by gas-liquid chromatography as an aid for the diagnosis of disseminated candidiasis . Both variables were observed as per-O-acetylated aldononitrile derivatives in each chromatographic run of sera from immunosuppressed rabbits experimentally infected with Candida albicans 3181A.

J Rheumatol, 1983 Jun, 10(3), 494 - 5
Fungal infection of prosthetic joints: a report of two cases; Goodman JS et al.; Two cases of yeast infection of prosthetic joints, caused by Torulopsis glabrata and Candida albicans are described . One case occurred 27 months after joint insertion . Neither patient had an underlying illness predisposing them to infection . Removal of the prosthetic device appears necessary for cure of such infection.

J Maxillofac Surg, 1983 Jun, 11(3), 124 - 7
Persistent mandibular infection in three patients with lazy and incompetent phagocyte syndromes; Foroozanfar N et al.; Three patients with the lazy phagocyte syndrome suffered from recurrent infections in the orofacial region which persisted despite treatment with antibiotics . All had neutrophil counts at the lower normal limits which did not increase after strenuous exercise or rise during infections . Tests of chemotaxis, random mobility and the skin window were abnormal . Ingestion and intracellular killing, however, were normal in one patient and abnormal in two . The findings are compatible with the lazy leucocyte syndrome but the symptoms were not manifest in early childhood as originally described by Miller et al . (1971), and the neutrophil counts were not as low as in his patients . Two of our patients also differed in showing a defective intracellular killing for Candida albicans . The lazy leucocyte syndrome should now be recognized to include different variants, some with late onset, a range in the degree of neutropenia, and some with defective ingestion and killing, though all possess a basic intrinsic defect of movement.

Eur J Clin Microbiol, 1983 Jun, 2(3), 206 - 12
Comparison of immunodiffusion and crossed-immunoelectrophoresis in the diagnosis of invasive candidiasis; Vanmali AN et al.; A retrospective single blind study was conducted to compare the efficacy of crossed-immunoelectrophoresis using concanavalin A intermediate gel with double immunodiffusion tests in the diagnosis of invasive candidiasis . On the basis of cytoplasmic antibody detection, crossed-immunoelectrophoresis with concanavalin A differentiated reliably between Candida albicans fungemia and invasive candida infection, whereas double immunodiffusion did not . With regard to sensitivity, specificity, and predictive value crossed-immunoelectrophoresis with concanavalin A was superior to double immunodiffusion . Analysis of double immunodiffusion precipitin bands revealed fuzzy and sharp precipitin bands which corresponded to mannan (fuzzy) and cytoplasmic (sharp) antibodies in the crossed-immunoelectrophoresis with concanavalin A assay . Therefore, the finding of sharp bands in the double immunodiffusion procedure supports the diagnosis of invasive candidiasis.

J Appl Bacteriol, 1983 Jun, 54(3), 383 - 9
The antimicrobial effect of dissociated and undissociated sorbic acid at different pH levels; Eklund T; The minimum inhibitory concentration of sorbic acid has been determined for Bacillus subtilis, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans . The inhibition was shown to be due to both undissociated and dissociated acid, and the effect of each has been calculated in accordance with a proposed mathematical model . Although the inhibitory action of undissociated acid was 10-600 times greater than that of dissociated acid, the latter caused more than 50% of the growth inhibition at pH levels above 6 for most of the organisms tested.

Arch Microbiol, 1983 Jun, 134(3), 251 - 3
Differences of asymmetrical division between the pseudomycelial and yeast forms of Candida albicans and their effect on multiplication; Yokoyama K et al.; Unlike asymmetrical division of budding yeast, the daughter cell in the pseudomycelial form of Candida albicans at division was nearly equal in size to the mother cell, it had a larger amount of protein, RNA and active protoplasm (cell size minus vacuolar volume) than the mother cell, and it budded earlier than the mother cell . Results presented here suggest that the cell size control over bud initiation found in budding yeasts is also applicable to the pseudomycelial cells of C . albicans if vacuolar volume is omitted from cell size.

Tsitologiia, 1983 Jun, 25(6), 707 - 10
{Acidification kinetics in macrophage phagosomes based on flow cytometric data}; Filatov AV et al.; Using flow cytofluorimetry, acidification in macrophages was studied during phagocytosis of yeast cells Candida albicans conjugated with FITC . Two phases of acidification were found: one corresponding presumably to yeast cell absorption on the macrophage surface, and the other one being due to cell incorporation into phagolysosomes . The phases are characterized by pH values of 6.3 +/- 0.5 and 4.5 +/- 0.5, respectively . Addition of 10 mM NH4Cl cancelled the observed acidification, whereas the presence of cytochalasin B (2 . 10(-5) M) prevented the very process of acidification.

Sabouraudia, 1983 Jun, 21(2), 93 - 8
Variability of the adherence of Candida albicans strains to human buccal epithelial cells: inconsistency of differences between strains related to virulence; Kearns MJ et al.; Adherence of Candida albicans to human buccal epithelial cells varied with the composition of the culture medium used to grow the fungus and the donor of epithelial cells, and even from day to day with the same fungal growth conditions and cell donor . Small differences in adherence were detected between four laboratory strains of C . albicans that differed in virulence for mice, and between three pairs of minimally subcultured isolates from cases of oral thrush and from the mouths of healthy donors . However the differences were not only small but did not consistently show that the adherence capacities of the strains virulent for mice or obtained recently from oral thrush were greater than those of the other strains.

J Clin Invest, 1983 Jun, 71(6), 1602 - 13
Specific in vitro antimannan-rich antigen of Candida albicans antibody production by sensitized human blood lymphocytes; Durandy A et al.; We have developed a new antigenic system for the induction of specific in vitro antibody response in man . The antigen used was purified from the cell wall of Candida albicans strain A and contained greater than 96% polysaccharide mannan . Peripheral blood mononuclear cells from Candida-sensitized donors produced specific antimannan antibodies during a 7-d culture in the presence of mannan absorbed with methylated bovine serum albumin . Two methods were used to detect antimannan antibody responses . Antimannan antibody-producing cells were identified by radioautography with tritiated mannan . Antibody concentration in culture supernatants was measured by an enzyme-linked immunosorbent assay . In both methods, specific IgM and IgG (but not IgA) antibodies were detected . The antibody production to mannan was specific, since an antigenically unrelated polysaccharide (pneumococcal antigen S III) did not bind to methylated bovine serum albumin-mannan-induced blast cells and did not induce antimannan antibody-containing cells . Furthermore, a pulse with an excess of unlabeled mannan abolished {3H}mannan binding, whereas an excess of unlabeled S III did not . Similarly, no antimannan antibody was obtained in influenza virus-stimulated cultures and mannan-stimulated cultures were not inducing antiinfluenza antibodies . The antimannan antibody production was shown to be a T cell-dependent phenomenon . The T helper effect appeared to be radiosensitive . It was under a genetic restriction as it occurred only in autologous or semi-identical but not in allogeneic situations . This system is relatively simple, reproducible, and well suited for the study of specific secondary in vitro antibody responses to polysaccharide antigens in humans.

Genetics, 1983 Jun, 104(2), 241 - 55
A genetic analysis of Candida albicans: isolation of a wide variety of auxotrophs and demonstration of linkage and complementation; Kakar SN et al.; Naturally occurring strains of Candida albicans appear to be diploid and heterozygous for a limited number of nutritional markers . Additional heterozygosity can be induced by treatment with mutagens; nitrous acid alone or in combination with UV is a potent mutagen in terms of both efficacy and efficiency in the production of a wide variety of mutations . Spheroplast fusion followed by regeneration on selective media revealed complementation among four histidine-requiring mutants analyzed . Some of the fusion products appeared to be stable prototrophs, whereas in others several kinds of segregants resulted, apparently due to chromosomal or nuclear elimination . The results are suggestive of both heterokaryosis as well as nuclear fusion . The procedures described can be successfully used for generating new mutants and studying allelism . Three sets of linkage relationships have been derived from evidence provided by concomitant appearance or cosegragation of several auxotrophic markers.

J Infect Dis, 1983 Jun, 147(6), 1070 - 7
Correlation of in vitro susceptibility test results with in vivo response: flucytosine therapy in a systemic candidiasis model; Stiller RL et al.; The in vitro susceptibility of Candida albicans isolates to flucytosine was compared to therapeutic effect in experimental murine candidiasis (candidosis) . Four groups of 10 isolates were chosen, based upon their broth dilution minimal inhibitory concentrations (MICs), from a group of 402 isolates from patients without prior flucytosine therapy . Group I MICs were less than 12.5 micrograms/ml after seven days, whereas group II, III, and IV MICs exceeded 12.5 micrograms/ml on days 7, 2, and 1, respectively . Pilot experiments selected challenge inocula of similar virulence . Mice were infected intravenously and given various flucytosine doses . Significant prolongation of survival correlated with MICs and with agar disk-diffusion zone diameters (P less than 0.05) . In vivo response to therapy was more favorable for group I isolates compared with group IV isolates (P less than 0.01) . The present study demonstrates in this animal model that in vitro susceptibility does correlate with in vivo response to therapy, although exceptions occur with individual isolates.

J Infect Dis, 1983 Jun, 147(6), 1036 - 40
Strain-related differences in pathogenicity of Candida albicans for oral mucosa; Allen CM et al.; Fifty female Sprague-Dawley rats were divided into five groups of 10 animals and were given a low concentration (0.01%) of tetracycline in drinking water . Four of the groups were orally inoculated weekly with the yeast Candida albicans for a period of 25 weeks . Each group received a different strain . Three of the four strains of yeast were consistently recovered upon culture of the oral cavity during the course of the study . Two of the strains produced grossly visible lesions (four of 10 and two of 10 animals) on the midline dorsal tongue, whereas no lesions were seen in the other two experimental groups or the control group . Clinical findings were supported histologically . These data suggest definite strain-related differences in mucosal pathogenicity for the lingual mucosa of rats among the strains of C . albicans studied.

Infect Immun, 1983 Jun, 40(3), 950 - 5
Influence of preformed antibody on the pathogenesis of experimental Candida albicans endocarditis; Scheld WM et al.; The influence of preformed antibody on the induction of experimental Candida albicans endocarditis was investigated by both in vitro and in vivo techniques . Preincubation of C . albicans with immune serum (raised in rabbits by intravenous injection of Formalin-killed yeast cells) decreased adhesion to the constituents of nonbacterial thrombotic endocarditis, e.g., fibrin plus platelets, in vitro . Two different methods, with radiolabeled or viable yeast cells, were confirmatory and demonstrated decreased adhesion of immune serum-treated C . albicans cells to 0 to 7.8% of control values (P less than 0.001) . These results correlated with protection from the development of C . albicans endocarditis in the immunized rabbits . The mean (+/- standard deviation) infectious dose for 50% of the animals was 10(5.29) +/- 10(0.07) in 48 control animals versus 10(7.11) +/- 10(0.22) in 37 immunized rabbits (P less than 0.001) . These studies suggest that humoral antibody may protect against C . albicans endocarditis, perhaps through inhibition of adhesion, a crucial early step in the pathogenesis of endocarditis.

J Infect Dis, 1983 Jun, 147(6), 1060 - 3
Ketoconazole and candidiasis: a controlled study; Hughes WT et al.; A double-blind, placebo-controlled study was undertaken to determine the efficacy of ketoconazole in the treatment of candidiasis . The drug was administered orally in the dosage of 200 mg/m2 of body surface per day for two weeks to cancer patients with oral candidiasis . Randomization in a 2:1 ratio provided 36 patients treated with ketoconazole and 20 managed with a placebo . Regression of visible lesions was achieved in 26 (72%) of 36 ketoconazole-treated and four (20%) of 20 untreated patients; eradication of culturable organisms occurred in 12 (36%) of 33 ketoconazole-treated and one (7%) of 14 untreated patients; and resolution of lesions plus eradication of Candida albicans occurred in nine (25%) of 36 ketoconazole-treated and one (5%) of 20 untreated patients . Although the therapeutic efficacy of ketoconazole was demonstrated for oropharyngeal candidiasis, the magnitude of its efficacy was less than that desired.

J Bacteriol, 1983 Jun, 154(3), 1033 - 9
Construction of a new yeast cloning vector containing autonomous replication sequences from Candida utilis; Hsu WH et al.; DNA sequences from the Candida utilis genome which, when cloned into a yeast integration plasmid (YIp5), confer on YIp5 the ability to replicate autonomously in Saccharomyces cerevisiae are described . Several recombinant plasmids which transform S . cerevisiae YNN27 to Ura3+ with an efficiency of 2 X 10(3) transformants per microgram of DNA were obtained . One of the recombinant plasmids, pHMR22 (6.6 kilobases) contains ars (autonomous replication sequence), which is homologous with two different DNA fragments of the C . utilis genome but has no detectable homology to total DNA from Candida albicans, Pachysolen tannophilus, or S . cerevisiae . Restriction and subcloning analyses of pHMR22 showed that Sau3A destroys the functions of cloned ars whereas there are no BamHI, PstI, SalI, HindIII, EcoRI, or PvuII sites in the region of ars which is required for its functional integrity . Thus, pHMR22 appears to be a useful vector for cloning desired genes in S . cerevisiae.

Infect Immun, 1983 Jun, 40(3), 1134 - 9
Hydroxamate siderophore production by opportunistic and systemic fungal pathogens; Holzberg M et al.; It has been suggested that siderophores may function as virulence factors . There have been few studies on production of siderophores by opportunistic and pathogenic fungi . We examined siderophore production by Absidia corymbifera, Aspergillus niger, Rhizopus arrhizus, Rhizopus oryzae, Blastomyces dermatitidis, Histoplasma capsulatum, Sporothrix schenickii, Candida albicans, and Trichophyton mentagrophytes . Fungi were cultured at 37 and 27 degrees C in a chemically defined low-iron media (0.2 microM Fe) . Culture supernatants were assayed for siderophores by two nonspecific methods {FeCl3 and Fe(ClO4)3} and three chemically specific assays (catechol, 2,3-dihydroxybenzoate, and hydroxamate) . All fungi secreted siderophores . Only siderophores of the hydroxamate type were found . More siderophore was produced at 27 degrees C than at 37 degrees C . The present study adds eight fungi to the list of known siderophore producers and confirms siderophore production by H . capsulatum.

Sabouraudia, 1983 Jun, 21(2), 99 - 112
Antigenic variations of Candida albicans in vivo and in vitro--relationships between P antigens and serotypes; Poulain D et al.; Serum samples from patients with candidosis and from rabbits experimentally infected with serotype B C . albicans strains consistently showed higher antibody titers against Candida strains with serotype A antigens than strains with serotype B antigens, in indirect fluorescent antibody tests . When sera from rabbits infected with C . albicans serotype B strains were absorbed with blastospores of the homologous strain they continued to react against strains of C . albicans serotype A and a C . tropicalis strain with serotype A antigens . Serotype A-specific antisera reacted against tissue forms of C . albicans serotype B in vivo and against serotype B germ tubes, but not their parent blastospores, in vitro . These findings suggest that C . albicans B serotype cells may sometimes express, in vitro or in vivo, one or several antigens so far considered as specific of serotype A . The results have implications for the classical concept of C . albicans serotypes and for the serological diagnosis of candidosis in relation with the previously described strain P variable antigens.

Med J Aust, 1983 May 14, 1(10), 480 - 1
Neonatal systemic candidiasis treated with miconazole and ketoconazole; Tudehope DI et al.; Three infants of very low birthweight, who contracted systemic Candida albicans infections while receiving neonatal intensive care, underwent therapy with intravenously administered miconazole and orally administered ketoconazole . The drugs proved to be effective against the systemic infections with C . albicans and were well tolerated by babies . However, further trials are necessary to confirm the efficacy of these drugs in newborn infants.

Pharmazie, 1983 May, 38(5), 308 - 10
Preparation and antimicrobial activity of some new bisquaternary ammonium salts; Imam T et al.; A series of new bisquaternary ammonium dibromides of the type N,N'-bis(decyldimethyl)-alpha, omega-alkanediammonium dibromides and N,N'-bis(4-aryloxybutyldimethyl)-1,6-hexane diammonium dibromides has been prepared and screened for antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida albicans . In the first group of compounds the connecting alkyl chain had 2 to 6, 8, 10 and 12 carbon atoms, in the second one in the 4-aryloxybutyl linkage the aryl was phenyl, p-methylphenyl, p-tert-butylphenyl-p-chlorophenyl-1-naphthyl and 2-naphthyl . The effect on the antimicrobial activity of the length of the hydrocarbon chain linking the two nitrogen atoms and the effect of replacing the long alkyl chain with substituted or unsubstituted 4-aryloxybutyl groups was studied.

Contact Dermatitis, 1983 May, 9(3), 201 - 4
Phototoxic and contact toxic reactions of the exocarp of sweet oranges: a common cause of cheilitis?
Volden G, Krokan H, Kavli G, Midelfart K.
Irritant skin reactions were produced within 1 h after application of the exocarp of sweet oranges or alcoholic extracts therefrom . Such reactions faded within 48 h . The exocarp, or extracts thereof, induced phototoxic reactions which were strongest at 72 h after exposure . The phototoxic reactions were only induced in natural blondes and only with some oranges . The in vivo phototoxic reactions were confirmed in vitro, causing a slight but clear photo-inhibition of Candida albicans . Only some oranges inhibited growth.

J Infect Dis, 1983 May, 147(5), 939 - 45
Treatment and prophylaxis of disseminated infection due to Candida albicans in mice with liposome-encapsulated amphotericin B; Lopez-Berestein G et al.; The toxicology of liposome-encapsulated amphotericin B in mice and its efficacy in the treatment and prophylaxis of systemic candidiasis in these animals were studied . The toxicology studies indicated that the maximal tolerated dose of free amphotericin B was 0.8 mg/kg of body weight and the 50% lethal dose (LD50) was reached at 1.2 mg/kg, while neither the maximal tolerated dose nor the LD50 for the liposomal amphotericin B was reached at a dose of 12 mg/kg . No abnormalities in blood chemistry or histology were observed in the animals injected with encapsulated amphotericin B, while the administration of free amphotericin B was associated with nephrocalcinosis and renal parenchymal edema . The encapsulated drug was as effective as the free drug when used in similar concentrations, while the animals treated with higher concentrations of liposomal amphotericin B (4 mg/kg) had a longer survival time . Thus, an improved therapeutic index resulted by encapsulating amphotericin B in liposomes.

Infect Immun, 1983 May, 40(2), 733 - 40
Immunomodulation by Blastomyces dermatitidis: functional activity of murine peritoneal macrophages; McDaniel LS et al.; Cell-mediated immunity plays the dominant role in the immune response of mice to Blastomyces dermatitidis infections . Since macrophages play an important role in cell-mediated immunity, the interactions between sensitized murine peritoneal macrophages and the yeast phase of B . dermatitidis were investigated . Scanning electron microscopy showed that the sensitized macrophages readily phagocytized B . dermatitidis yeast cells . In addition, there appeared to be activation of metabolic pathways within the sensitized macrophages, as indicated by increased chemiluminescence activity during phagocytosis . Sensitized macrophages were significantly better at controlling intracellular proliferation of the yeast cells when compared to nonsensitized cells . This was determined by disruption of macrophages and plating for viable yeasts . Scanning electron microscope observations offered further substantiation . Experiments with Candida albicans indicated that B . dermatitidis non-specifically activated macrophages . At 2 h postphagocytosis, 30% fewer C . albicans in B . dermatitidis-activated macrophages were able to form germ tubes . These studies demonstrated the multiple potential of activated macrophages with regard to their functional activity.

J Gen Microbiol, 1983 May, 129 (Pt 5), 1577 - 82
Calcofluor white alters the assembly of chitin fibrils in Saccharomyces cerevisiae and Candida albicans cells; Elorza MV et al.; In the presence of calcofluor white, budding scars and dividing cross-walls of Saccharomyces cerevisiae exhibited fluorescence, indicating that the brightener was a specific marker of fungal chitin . In addition, incubation of cells in the presence of the brightener did not stop protein and wall-polymer formation, but abnormal deposition of chitin occurred . Chitin synthesis was normal in regenerating protoplasts of Candida albicans in the presence of calcofluor, but formation of the crystalline lattice was blocked . These results suggest that crystallization of nascent subunits may occur by a self-assembly mechanism that was blocked by the stain.

J Gen Microbiol, 1983 May, 129 (Pt 5), 1569 - 75
31P nuclear magnetic resonance study of growth and dimorphic transition in Candida albicans; Cassone A et al.; A 31P NMR study of the fungal pathogen Candida albicans was carried out . Yeast-form cells at different phases of growth, as well as germ tubes and hyphae were examined . In all cases, the NMR spectra showed well separated resonance peaks arising from phosphorus-containing metabolites, the most prominent being attributable to inorganic phosphate (Pi) polyphosphates, sugar phosphates and mononucleotides, NAD, ADP and ATP . Relevant signals were also detected in the phosphodiester region . The intensity of most signals, as measured relative to that of Pi, was clearly modulated both at the different phases of growth and during yeast-to-mycelium conversion, suggesting significant changes in the intracellular concentration of the corresponding metabolites . In particular, the intensity of the polyphosphate signal was high in exponentially growing, yeast-form cells, then progressively declined in the stationary phase, was very low in germ tubes and, finally, undetectable in hyphae . NMR spectral analysis of the Pi region showed that from early-stationary phase, Pi was present in two different cellular compartments, probably corresponding to the cytoplasm and the vacuole . From the chemical shift of Pi, the pH values of these two compartments could be evaluated . The cytoplasmic pH was generally slightly lower than neutrality (6.7-6.8), whereas the vacuolar pH was always markedly more acidic.

Exp Cell Res, 1983 May, 145(2), 255 - 64
The influence of contact guidance on chemotaxis of human neutrophil leukocytes; Wilkinson PC et al.; Chemotaxis of human neutrophil leukocytes moving on or in aligned 3D fibrin gels is more efficient if the cells are moving along the axis of fibre alignment than if they have to cross the fibres . This was shown by using two assays, one in which the cells were responding to a distant (600 micrometers) gradient source diffusing from a filter paper impregnated with formyl-Met-Leu-Phe and incorporated into the gel, the other in which the cells were responding to nearby (20--30 micrometers) Candida albicans spores in serum . In the former assay, impairment of chemotaxis across the axis of fibre alignment was highly significant . In the latter, cells showed efficient chemotaxis to the spores, but took more irregular paths when crossing the aligned fibres than when running along them . Neutrophils show contact guidance in aligned collagen or fibrin gels (Wilkinson et al., Exp cell res 140 (1982) 55) {1}, thus the cells were subjected simultaneously to two directional cues in these experiments, one the chemotactic gradient and the other a contact guidance field . These cues may reinforce or interfere with each other depending on their relative orientation . Since many tissues in vivo show alignment or more complex forms of patterning, tissue architecture is likely to be an important determinant of the efficiency of cellular mobilization in inflamed or infected sites.

J Reticuloendothel Soc, 1983 May, 33(5), 381 - 90
The influence of a gastrointestinal microflora on natural killer cell activity; Bartizal KF et al.; These studies demonstrate that the natural cytotoxicity of BALB/c mouse spleen cells for 51Cr-labeled YAC-1 cells can be significantly enhanced by microorganisms in the alimentary tract . Spleen cells from germfree BALB/c mice, euthymic, athymic, or non-nude background (+/+), had natural cell-mediated cytotoxicity for YAC-1 cells . Intestinal colonization with a few (flora-defined) or many (complex flora-conventionalized) microorganisms significantly enhanced natural cell-mediated cytotoxicity of athymic and euthymic mice over their germfree counterparts . Conversely, colonization of the alimentary tract of athymic and euthymic germfree mice with a pure culture of Candida albicans or colonization with Candida and a Bacillus sp . did not enhance natural cell-mediated cytotoxic activity over germfree levels . Spleen cells from germfree athymic mice were significantly more cytotoxic than spleen cells from germfree BALB/c mice that did not carry the nude gene (ie, +/+) . In the germfree or gnotobiotic state, no difference in natural killer cell activity was evident between athymic (nu/nu) and heterozygous (+/nu) littermate mice; however, athymic (nu/nu) flora-defined or conventionalized mouse spleen cells were significantly more cytotoxic for YAC-1 cells than splenocytes from flora-defined or conventionalized heterozygous (+/nu) littermates . Spleen cells from BALB/c mice that were athymic (nu/nu) and colonized with a complex microbial flora (ie, conventionalized) had the highest percentage of cytotoxicity, at three different effector to target ratios, for YAC-1 cells . These studies indicate that the intestinal microflora can alter murine natural cell-mediated cytotoxicity.

J Fam Pract, 1983 May, 16(5), 919 - 24
Colonization of Candida albicans in vagina, rectum, and mouth; Bertholf ME et al.; To better understand the frequency of appearance, the density of growth, and the most common sites in which female patients harbor Candida albicans, a study was initiated of all patients receiving a pelvic examination for any reason at a solo family practice office . From February 1980 to November 1981, 341 pelvic examinations were accompanied by cultures and colony counts of the vagina, rectum, and mouth . A semiquantitative method adapted to Microstix-Candida (Ames Company) was utilized . Only 39 percent of all examinations had negative cultures in all three sites . Twenty-three percent of the positive cultures for C albicans were found from the vagina, 41 percent from the rectum, and 34 percent from the mouth . Incidence of colonization in any site did not vary significantly from 16 to 75 years of age . Negative rectal colonization was associated with lower vaginal colony counts and less frequent vaginal symptomatology . Relatively high vaginal colony count was associated with symptomatic vaginal candidiasis.

Boll Soc Ital Biol Sper, 1983 Apr 30, 59(4), 532 - 4
{Incidence of oral candidiasis in a sample group of diabetics}; Amato R et al.; The recurrence of Candida albicans in the oral cavity of diabetic subjects is examined in connection with the capacity of dismetabolic diseases, and diabetes in particular, to support the development of various mycoses . Results from the study of (not - saliva samples taken from) 50 diabetic but stomatologically healthy subjects show that Candida albicans was present in half of the cases examined and was more frequent in females than in males (15 and 10 cases, respectively) . Oral cavity pH was also found to be lower in Candida albicans subjects than in normal cases.

Boll Soc Ital Biol Sper, 1983 Apr 30, 59(4), 529 - 31
{Presence of Candida albicans in the oral cavity of healthy subjects}; Amato R et al.; The influence of possible changes in bacterial flora in the etiology of periodontal disease assessed during a study of saprophitism of Candida albicans in the oral cavity is reported . Three saliva samples, each from each of 50 healthy subjects not on drugs, taken prior to breakfast and after careful cleaning of the oral cavity the previous evening were subjected to bacterioscopic examination both immediately and after culturing on Sabouraud medium . pH levels were also determined . 17 subjects, of which females predominated, (12 cases compared to 5 male cases) were found to be C.a carriers.

Urology, 1983 Apr, 21(4), 421 - 3
Anuria from candida pyelonephritis and obstructing fungal balls; Khan MY; A premature newborn male required intensive care and prolonged antibiotic therapy for respiratory distress . Acute renal failure developed from bilateral obstructive candida pyelonephritis complicating systemic Candida albicans infection . Necropsy also revealed organizing subarachnoid hematoma and granulomatous candida meningoencephalitis.

Ann Acad Med Singapore, 1983 Apr, 12(2 Suppl), 416 - 9
Delayed hypersensitivity in squamous cell carcinoma of the oral cavity; Das SN et al.; Delayed hypersensitivity response to Dinitrochlorobenzine (DNCB), Purified Protein Derivative (PPD) and Candida albicans abstract (Dermatophytin 'O') was observed in 60 patients of squamous cell carcinoma of the oral cavity and 40 normal controls . The response to all these three antigens were significantly impaired in cancer patients as compared to normal controls . PPD and Dermatophytin 'O' response showed progressive decline with increasing tumour burden . Patients with well differentiated tumours responded well to all these three antigens as compared to those with poorly differentiated tumours.

J Gen Microbiol, 1983 Apr, 129 (Pt 4), 1133 - 9
Differential protein synthesis in Candida albicans during blastospore formation at 24.5 degrees C and during germ tube formation at 37 degrees C; Ahrens JC et al.; To identify proteins synthesized during blastospore to germ tube transformation in Candida albicans, membrane and cytoplasmic protein fractions labelled with 14C were analysed by SDS-PAGE and autoradiography . Four cytoplasmic proteins were detected in pulse-labelled lysates prepared from cells forming blastospores and germ tubes at 37 degrees C, but not in pulse-labelled lysates prepared from cells forming blastospores at 24.5 degrees C . Three proteins detectable in 24.5 degrees C lysates were diminished in 37 degrees C lysates.

Eur J Obstet Gynecol Reprod Biol, 1983 Apr, 15(1), 37 - 43
Candida albicans strain types from the genitalia of patients with and without Candida infection; Odds FC et al.; The strain phenotypes of 266 C . albicans isolates from patients attending a genitourinary clinic were determined on the basis of 9 biochemical tests . Analysis of the strain patterns of isolates from the genitalia showed that there were no statistically significant differences between types associated with clinically overt Candida infection and types isolated in the absence of symptoms of candidosis . This finding accords with the traditional view of C . albicans as an opportunistic pathogen, rather than a species containing some strains of high virulence . In cases where isolations were made from the same patient at different times, or from different anatomical sites in the same patient, it was found that usually, but not always, a patient carried the same phenotype at different sites and different times . Similarly, the same strain type was isolated from the genitalis of both partners in a majority of instances where strains were isolated from consorts; however, this was not the case for a substantial minority of couples, particularly in those where high promiscuity appeared to promote considerable mixture and interchange of the C . albicans genital microflora.

J Ultrastruct Res, 1983 Apr, 83(1), 48 - 57
Reorganization of membrane ergosterol during cell fission events of Candida albicans: a freeze-fracture study of distribution of filipin-ergosterol complexes; Sekiya T et al.; The redistribution of ergosterol molecules which occurs during bud and germ tube formation (dimorphism) in Candida albicans was studied using filipin, a sterol-specific antibiotic, and examined by the freeze-fracture technique . When cells were fixed in a glutaraldehyde solution containing 50 micrograms/ml of filipin, filipin-ergosterol complexes, which were recognized as either pits on the exoplasmic fracture face or protuberances on the protoplasmic fracture face, were homogeneously distributed on the yeast plasma membranes . The plasma membrane of young budding yeast cells demonstrated few filipin-ergosterol complexes compared to the parent yeast plasma membrane . In addition, at a certain time during enlargement of budding yeast cells, the complexes became virtually absent from the constricted region between daughter and parent yeast cell . On the other hand, when germ tubes emerged as cylindrical outgrowths from the parent yeast cells, filipin-ergosterol complexes were heterogeneously redistributed on the plasma membrane . These results suggest that ergosterol molecules may be in lower concentration in the plasma membrane at the constricted region of yeast cell than elsewhere on the plasmalemma of the yeast cell.

Infect Immun, 1983 Apr, 40(1), 46 - 55
Correlation between in vivo and in vitro studies of modulation of resistance to experimental Candida albicans infection by cyclophosphamide in mice; Bistoni F et al.; Mice receiving a single injection of cyclophosphamide (150 mg/kg) 1 to 6 days before inoculation with viable Candida albicans showed an increased susceptibility to the challenge accompanied by a reduction in peripheral blood polymorphonuclear leukocytes and lymphocytes as well as in spleen cellularity . Several immunological in vitro functions also appeared to be dramatically depressed . Most of these hematological and functional parameters returned to control values by day 9 after cyclophosphamide administration, at a time when resistance to C . albicans infection appeared to be unchanged . However, when exposure to cyclophosphamide occurred 12 to 21 days before inoculation with the live yeast, enhanced resistance was observed with the majority of the animals surviving challenge . To gain some insight into the mechanisms underlying this late increase in resistance to C . albicans infection after cyclophosphamide administration, we analyzed a series of immunological functions, including the in vitro candidacidal activity of polymorphonuclear neutrophils and plastic-adherent and nonadherent spleen cells as well as the activity of natural killer cells and alloreactive T lymphocytes . The results show that a numerical rebound of blood polymorphonuclear neutrophils and the appearance of a highly candidacidal cell population in the spleen may be among the factors underlying the late increase in resistance to C . albicans after administration of cyclophosphamide.

Am J Public Health, 1983 Apr, 73(4), 450 - 2
Quantitative relationships of Candida albicans infections and dressing patterns in Nigerian women; Elegbe IA et al.; Candida albicans colony counts were far higher in patients with vaginitis wearing tight fitting clothing than in patients wearing loose fitting clothing . In Ile-Ife, Nigeria, tight fitting dresses, woolen and corduroy jeans, coupled with nylon underwear, appear to create an environment favorable to Candida albicans colonization.

J Antimicrob Chemother, 1983 Apr, 11(4), 381 - 3
Comparison of miconazole- and ketoconazole-induced release of K+ from Candida species; Beggs WH; Relatively high concentrations of miconazole caused immediate and rapid release of K+ from strains of Candida albicans and Can . parapsilosis . Ketoconazole did not . These results support the recent hypothesis that ketonocazole, unlike related antifungal imidazole-containing drugs, cannot exert a direct membrane damaging effect.

Infect Immun, 1983 Apr, 40(1), 97 - 102
Generation of hydrogen peroxide by Candida albicans and influence on murine polymorphonuclear leukocyte activity; Danley DL et al.; Iodide fixation by murine polymorphonuclear leukocytes (PMN) incubated with viable Candida albicans blastoconidia increases directly with yeast cell concentration up to about 3 x 10(6) cells per ml, but above this concentration bound activity declines dramatically . To understand the basis for this decline, we examined the oxidative metabolism of fungi and stimulated PMN and found some remarkable similarities between these cell types . Both produced 14CO2 when incubated with {1-14C}glucose, both reduced cytochrome c, and both fixed radiolabeled iodide, although the fungi required exogenous lactoperoxidase . In dose-response experiments, iodination by fungi with lactoperoxidase was identical to that with PMN, i.e., the maximum bound activity occurred in cultures with 10(6) to 3 x 10(6) blastoconidia per ml . Iodination by fungi with lactoperoxidase was reduced when blastoconidia were incubated at 25 degrees C or in the presence of catalase and the metabolic inhibitors rotenone, antimycin A, and 2-deoxyglucose . Results from assays for oxidation of scopoletin and o-dianisidine showed that 10(6) blastoconidia in 1.0 ml of medium released 0.5 to 0.7 nmol of H2O2 after 1 h, but 3 X 10(6) and 10(7) cells released significantly less H2O2 . These results suggest that iodide fixation by PMN and low numbers of fungal cells may reflect a cooperative effort, with fungi generating some H2O2 that reacts with the myeloperoxidase released from the PMN . With high concentrations of blastoconidia, H2O2 activity appeared to be specifically inhibited, possibly to protect fungal cells from damage.

Biochim Biophys Acta, 1983 Mar 23, 729(1), 85 - 9
Effect of phosphatidylserine enrichment on amino acid transport in yeast; Trivedi A et al.; A 1.5- to 3.5-fold accumulation of phosphatidylserine was observed when Candida albicans and Saccharomyces cerevisiae cells were grown in the presence of hydroxylamine, a known inhibitor of phosphatidylserine decarboxylase . However, as compared to S . cerevisiae cells, the levels of phosphatidylcholine and phosphatidylethanolamine were much lower in C . albicans cells . The enrichment of phosphatidylserine selectively affected the transport of several amino acids.

Antimicrob Agents Chemother, 1983 Mar, 23(3), 356 - 9
Silver-nylon: a new antimicrobial agent; Deitch EA et al.; The potential effectiveness of a silver nylon (SN) fabric as an antimicrobial agent was evaluated in a series of in vitro experiments . The results indicated that silver ions from the SN fabric penetrated 2 mm of agar and killed a challenge of 6.9 X 10(7) Pseudomonas aeruginosa, 4.1 X 10(7) Staphylococcus aureus, and 1.4 X 10(7) Candida albicans organisms per cm2 of SN fabric after 24 h of incubation at 37 degrees C . To determine some of the microbicidal limits of the SN, the distance between the SN fabric and the microbial challenge was increased . Increasing the height of the agar column overlying the SN fabric diminished the inhibitory effect of SN on microbial growth . For each increase in agar height of 2 mm, up to a total height of 8 mm, the effectiveness of SN to inhibit microbial growth decreased by a factor of 10 . This distance-related decrease in the microbicidal ability of SN could be overcome by placing the SN fabric in contact with the agar column for 24 to 72 h before microbial challenge . On the basis of these experiments, it appears that SN is an effective antimicrobial agent, although further work must be performed before it is applied clinically.

Immunology, 1983 Mar, 48(3), 529 - 35
Effect of angiotensin II on macrophage functions; Foris G et al.; Angiotensin II (At II) has been shown to inhibit in vitro the IgG2a-mediated rosette formation of 51Cr-sheep red blood cells (SRBC) by provoked peritoneal macrophages (PM) at 10(-5)-10(-6) M concentrations . The decreased rosette formation was associated with an increased phagocytosis . It was found that the enhanced rosette formation at 10(-7) M hormone concentration was followed by diminished phagocytosis via Fc gamma receptors (R) . Processes mediated through Fc microR were affected only after incubation with 10(-5) M of At II . The attachment and subsequent phagocytosis through C3bR was markedly enhanced by At II in a dose-dependent way . Thus, the relative phagocytosis (RP) through both FcRs was significantly enhanced by 10(-5), i.e . by 10(-5)-10(-6) M of At II, but lowered at 10(-7) M hormone concentration . In addition, there was no RP enhancing effect of At II after preincubation with 10(-5) M of indomethacin (IM), indicating the significance of prostaglandins (PG) in the hormone effect . The medium containing 5 mM of EGTA diminished both the RP enhancing and inhibiting effects of At II . The RP mediated by C3b was not affected by At II, IM or EGTA . The intracellular killing capability, measured by chromium release from Candida albicans, was not altered or even slightly diminished after At II treatment of PMs.

Cell Immunol, 1983 Mar, 76(2), 243 - 52
Physiochemical characterization of human histamine-induced suppressor factor; Rocklin RE et al.; A product of histamine-stimulated human lymphocytes, histamine-induced suppressor factor or HSF, was characterized by enzyme treatment, sensitivity to reduction and alkylation, by molecular sieve chromatography, and by polyacrylamide gel electrophoresis . HSF was found to have a wide pH stability (pH 3-10), sensitivity to temperatures greater than 80 degrees C, and to have the properties of a glycoprotein by virtue of its sensitivity to chymotrypsin, trypsin, sodium periodate, and neuraminidase . HSF did not appear to have a serine group(s) in its "active" site since its biologic activity remained intact following treatment with an irreversible serine esterase inhibitor (phenylmethylsulfonyl fluoride) . Further, HSF did not appear to have inter- or intra-molecular disulfide linkages because treatment with denaturing and/or reducing agents, followed by alkylation, did not significantly alter its activity . Molecular sieve chromatography employing Sephadex G-100 revealed an apparent molecular weight for HSF of 25-40,000 . Electrophoresis of HSF in polyacrylamide gels at pH 8.7 under nonreducing conditions revealed two regions of activity, one region migrating with albumin and the other region anodal to albumin . In addition to suppressing lymphocyte proliferation, the 25-40,000 Mr Sephadex G-100 fractions also inhibited the production of leukocyte inhibitory factor . Of particular interest, gel filtration of supernatants generated by stimulating mononuclear cells with either histamine, dimaprit (but not 2-pyridylethylamine), concanavalin A, or candida albicans resulted in similar elution profiles with regard to inhibition of lymphocyte proliferation . That is, 25-40,000 Mr fractions of supernatants generated by each stimulant suppressed lymphocyte proliferation to a similar degree . The latter findings provide indirect evidence that T lymphocytes, triggered in response to antigen-specific and nonspecific stimuli, elaborate suppressor molecules capable of modulating T-cell function that share certain similarities.

Biochem Int, 1983 Mar, 6(3), 409 - 17
Transport of purine, pyrimidine bases and nucleosides in Candida albicans, a pathogenic yeast; Rao TV et al.; Saturable, carrier mediated transport mechanism of adenine, guanine, thymine, uracil, adenosine, inosine, thymidine and uridine has been characterized in Candida albicans cells . Analysis of intracellular contents at short and long time intervals and kinetic data revealed that the uptake of all these bases and their nucleosides is independent of phosphoribosyltransferases and phosphorylases and their metabolic conversion starts only after an initial lag of 1-2 minutes . On the basis of competition experiments, different common and specific transport systems have also been identified.

Sabouraudia, 1983 Mar, 21(1), 49 - 57
Induction and morphogenesis of chlamydospores in an agerminative variant of Candida albicans; Torosantucci A et al.; A strain of Candida albicans that did not form germ tubes was endowed with a pronounced ability for massive production of chlamydospores under appropriate environmental conditions . Development of chlamydospores was induced by N-acetyl hexosamines, especially N-acetyl-D-glucosamine, and this induction did not depend on non-specific utilization of N-acetyl hexosamines as metabolic sources nor did it correlate with induction of germ-tube formation . Formation of chlamydospores in N-acetyl hexosamine-agar medium occurs through a multiplication stage (10-12 h) consisting of a few cycles of budding leading to short, "pseudo-hypha-like" structures, followed by progressive differentiation of most cells into young chlamydospores (16-18 h) which go to complete maturation in 36-48 h . There were marked differences in chlamydospore formation among different strains of C . albicans but, when induced, the morphology and kinetics of sporulation were identical in all strains . This study shows that chlamydospore formation is not necessarily associated with the mycelial phase and suggests that N-acetyl hexosamines may induce sporulation by controlling endogenous metabolism rather than through products of their own metabolism.

Obstet Gynecol, 1983 Mar, 61(3 Suppl), 21S - 24S
Perinatal infection with Torulopsis glabrata: a case associated with maternal sickle cell anemia; Sander CH et al.; Torulopsis glabrata is a yeast of low virulence and commensal within the female genitourinary tract . The first case of congenital infection with Torulopsis glabrata was reported in 1980 . An additional example of perinatal Torulopsis infection which is associated with maternal sickle cell anemia is reported . The most common source of congenital fungus infection is Candida albicans . Differences in morphology between T glabrata and C albicans are apparent, particularly the pathologic response within the placenta . Pathogenicity in this case may be associated with increased susceptibility to infection in patients with sickle cell anemia.

J Med Chem, 1983 Mar, 26(3), 442 - 5
Synthesis of (E)-1-(5-chlorothien-2-yl)-2-(1H-imidazol-1-yl)ethanone 2,6-dichlorophenylhydrazone hydrochloride, a novel, orally active antifungal agent; Dyer RL et al.; The preparation, determination of isomeric configuration, and antifungal properties of (E)-1-(5-chlorothien-2-yl)-2-(1H-imidazol-1-yl)ethanone 2,6-dichlorophenylhydrazone hydrochloride (1) are described . In vitro, compound 1 has been shown to have activity against Candida albicans comparable with miconazole . When administered orally to animals with experimentally induced vaginal candidiasis or systemic candidiasis, compound 1 produced results approaching those produced by ketoconazole . In addition, topical administration of compound 1 to rats with vaginal candidiasis produced results comparable with those produced by similar administration of clotrimazole . Unlike ketoconazole, which is active by a mechanism that is essentially fungistatic, compound 1 shares with miconazole a mode of action that is fungicidal . However, unlike miconazole, compound 1 exhibits activity following oral administration . Compound 1 has been found to be negative in the Ames test.

Infect Immun, 1983 Mar, 39(3), 1354 - 60
Modulation of Candida albicans attachment to human epithelial cells by bacteria and carbohydrates; Centeno A et al.; The effects of carbohydrates (mannose and dextrose) . Escherichia coli 07KL . and Klebsiella pneumoniae on Candida albicans attachment to epithelial cells was studied . Dextrose had no effect on yeast attachment to epithelial cells . Conversely, mannose significantly decreased both yeast and piliated bacterial attachment (E . coli 07KL, heavily piliated K . pneumoniae) whereas having no effect on nonpiliated K . pneumoniae attachment to epithelial cells . The number of yeasts attaching to epithelial cells was enhanced by preincubation of epithelial cells with piliated strains of bacteria, whereas preincubation with nonpiliated strains of bacteria had no effect on yeast attachment . Scanning electron microscopy showed that piliated bacteria and yeasts were juxtaposed on the epithelial cell surface . These data suggest that certain piliated strains of bacteria can enhance C . albicans attachment to epithelial cells and that type 1 pili of bacteria can be a factor in the enhanced attachment of C . albicans to epithelial cells.

Doc Ophthalmol, 1983 Feb 28, 55(1-2), 63 - 71
Candida endophthalmitis in heroin addicts; Hogeweg M et al.; The clinical course of endophthalmitis, presumably due to Candida albicans, in nine eyes of heroin addicts is described . In six of the seven eyes in which pars plana vitrectomy was performed the diagnosis was confirmed by the cultivation of Candida albicans from the rinsing fluid . Both purely intraocular treatment and a combination of local and systemic antimycotic therapy caused the intraocular infection to disappear . In this small group of patients the results were most favourable when treatment was started early.

Postgrad Med, 1983 Feb, 73(2), 255 - 62
Vaginal infections . How to identify and treat them; Schneider GT; Vaginal infection occurs at some time in the majority of women . Most such infections are caused by Candida albicans, Trichomonas vaginalis, and Gardnerella (Hemophilus) vaginalis . Some less common--but in many cases increasingly prevalent--causes include herpes-virus type 2, papillomavirus, Chlamydia trachomatis, Mycoplasma T strains, and toxic shock syndrome.

Am J Clin Pathol, 1983 Feb, 79(2), 200 - 5
Diagnostic value of monitoring kinetics of antibody responses in candidiasis by a solid-phase radioimmunoassay; Mauch H; A solid-phase radioimmunoassay was used to monitor antibody binding to cytoplasmic antigens of Candida albicans in sera from patients with superficial or deep-seated candidiasis over extended observation periods . Healthy persons showed a constant level of Candida antibodies . Patients with superficial candidiasis or colonization generally had a slow, but significant rise; patients with presumptive and proven systemic candidiasis, however, developed rapid rises (up to forty-fold) of antibody levels within a few days . This method permitted the kinetics of antibody response to be followed and, thus, appeared to aid in the differentiation among the various forms of candidiasis.

J Gen Microbiol, 1983 Feb, 129 (Pt 2), 431 - 8
Virulence for mice of a proteinase-secreting strain of Candida albicans and a proteinase-deficient mutant; Macdonald F et al.; A proteinase-deficient mutant of Candida albicans, M12, was produced by nitrosoguanidine mutagenesis of a proteinase-producing strain, ATCC 28366 . The mutant was phenotypically identical to its parent in nearly all biochemical and morphological characteristics except proteinase production . The mutant was considerably less lethal than the parent when inoculated intravenously into mice and lower counts of C . albicans were recovered from the organs of mice infected with the mutant . Both strains were phagocytosed and killed to a similar extent by human and murine polymorphonuclear leukocytes when the yeasts were grown in a medium that did not induce proteinase production . However, in a proteinase-inducing medium, ATCC 28366 was phagocytosed and killed less well than M12 . These results indicate that proteinase secretion by C . albicans is one factor determining the virulence of the species, but that other virulence factors are also involved in the pathogenesis of systemic candidosis.

J Cell Biol, 1983 Feb, 96(2), 486 - 93
Filament ring formation in the dimorphic yeast Candida albicans; Soll DR et al.; Stationary phase cultures of Candida albicans inoculated into fresh medium at 37 degrees C synchronously from buds at pH 4.5 and mycelia at pH 6.5 . During bud formation, a filament ring forms just under the plasma membrane at the mother cell-bud junction at roughly the time of evagination . A filament ring also forms in mycelium-forming cells, but it appears later than in a budding cell and it is positioned along the elongating mycelium, on the average 2 microns from the mother cell-mycelium junction . Sections of filament rings in early and late budding cells and in mycelia appear similar . Each contains approximately 11 to 12 filaments equidistant from one another and closely associated with the plasma membrane . In both budding and mycelium-forming cells, the filament ring disappears when the primary septum grows inward . The close temporal and spatial association of the filament ring and the subsequent chitin-containing septum suggests a role for the filament ring in septum formation . In addition, a close temporal correlation is demonstrated between filament ring formation and the time at which cells become committed to bud formation at pH 4.5 and mycelium formation at pH 6.5 . The temporal and spatial differences in filament ring formation between the two growth forms also suggest a simple model for the positioning of the filament ring.

J Invest Dermatol, 1983 Feb, 80(2), 93 - 7
Activation of complement by Pityrosporum orbiculare; Sohnle PG et al.; The ability to activate complement in human serum was evaluated for the two yeast-like organisms Pityrosporum orbiculare, the presumed etiologic agent of tinea versicolor, and Candida albicans . Complement activation was measured by: (a) using inhibition of rabbit red blood cell lysis by human serum after incubation with the organisms, and (b) quantitation of the amount of C3 deposited on the surface of the yeast by an enzyme-linked immunoabsorbent assay . It was found that both organisms had approximately equal ability to activate complement in normal serum or serum having only the alternative pathway intact, even though extracts of C . albicans contained significantly greater amounts of both carbohydrate and antigenic material capable of combining with the antibody present in normal human serum . The marked difference in inflammation in the cutaneous lesions produced by these two organisms does not appear to be related to their complement-activating ability and is more likely due to some other factor such as differences in invasiveness or in ability to elicit other immunologic reactions.

J Invest Dermatol, 1983 Feb, 80(2), 133 - 5
Antibodies to Pityrosporum orbiculare in patients with tinea versicolor and controls of various ages; Faergemann J; Sera from patients with tinea versicolor and controls of various ages were investigated with the indirect immunofluorescence technique for antibodies against Pityrosporum orbiculare, the etiologic agent of tinea versicolor . No differences in titers were observed between patients and adult controls . Also, there were no differences in antibody titers in the patient group with regard to age and sex, or to duration and distribution of lesions . A statistically significant difference in antibody titers was observed between adult controls and children, particularly the youngest . Antibodies against Candida albicans from randomly selected sera from the same groups showed the same tendency, although only statistically significant when children of 5 years or younger were compared with adult controls . This investigation indicates that although P . orbiculare is capable of inducing antibodies, these are not correlated to tinea versicolor but occur when an individual becomes colonized with the organism.

Am J Med, 1983 Jan 24, 74(1B), 23 - 9
Long-term therapy of chronic mucocutaneous candidiasis with ketoconazole: experience with twenty-one patients; Horsburgh CR Jr et al.; Our experience in the treatment of chronic mucocutaneous candidiasis with ketoconazole is reviewed . Of 21 patients, 15 have evidence of deficient cellular immunity and eight have endocrine abnormalities . Six patients had concurrent dermatophytosis or chromomycosis . All patients responded to treatment . Mucosal lesions improved in 6.7 +/- 0.5 days and cutaneous lesions responded to 22.7 +/- 5.1 days . The responses by infected nails were more variable (mean response time 92.4 +/- 14.4 days) . Concurrent dermatophytoses did not prolong response times . Adverse effects were infrequent: one patient had drug-induced hepatitis and two patients became hypertensive . The relationship of hypertension to ketoconazole treatment is unclear . One patient was able to remain in remission after treatment was discontinued . Two patients had relapses while on treatment . Candida albicans isolated from these patients was highly resistant to ketoconazole in vitro . We conclude that ketoconazole is an effective and well-tolerated drug for the treatment of the infectious component of chronic mucocutaneous candidiasis.

Am J Med, 1983 Jan 24, 74(1B), 2 - 8
The mechanism of action of the new antimycotic ketoconazole; Borgers M et al.; Ketoconazole is one of the new members of the imidazole series with a broad-spectrum antifungal profile . Although sharing its basic active principles with the other imidazoles, ketoconazole obtains its superior in vivo activity mainly from its good oral absorption and its lower degree of inactivation once absorbed . Its selective toxicity for yeasts and fungi is found to be primarily linked to the inhibition of ergosterol biosynthesis and to interference with other membrane lipids . In vitro growth studies revealed that ketoconazole's activity was more pronounced against the invasive morphogenetic form than against the saprophytic form of Candida albicans, which at least partly explains its prominent in vivo potency . At extremely low concentrations (10 ng/ml-1) ketoconazole prevents the development of the very form that is responsible for the expression of clinical symptoms . In contrast to other imidazoles, ketoconazole's action on the morphogenesis of the organism is not influenced by serum . The synergistic action with host defense cells, as demonstrated in culture systems, is another inherent property of this drug and may have a great impact on the eradication of systemic fungal infections . These effects of ketoconazole have been studied in a variety of fungal organisms with the aid of phase-contrast, scanning, and transmission electron microscopy in order to characterize ketoconazole's profile in comparison to the other imidazole derivatives.

Poumon Coeur, 1983, 39(2), 87 - 93
{Bronchopulmonary pathology with hypereosinophilia of fungal origin (excluding allergic bronchopulmonary aspergillosis)}; Lahoute C et al.; Five cases of eosinophil lung are reported in which the fungus responsible for the affection was not Aspergillus . Documented data include reports on 19 similar cases with a clinical picture suggestive of allergic bronchopulmonary aspergillosis but with negative tests for Aspergillus . The various fungal species isolated included Candida albicans, Penicillium, Geotrichum candidum, Stemphylium lanuginosum, Culvularia lunata, and Drechsleria hawaiensis . Diagnostic criteria are discussed, with particular emphasis on the importance of the inhalation provocation test, as well as possible efficacy of antifungal treatment.

Clin Cardiol, 1983 Jan, 6(1), 37 - 40
Reliability of two-dimensional echocardiography in diagnosing fungal endocarditis; Sarma R et al.; Although the techniques of M-mode and two-dimensional (2D) echocardiography (echo) have been found to be useful in patients with bacterial endocarditis, the 2D findings of fungal endocarditis are not known . In this report, we present the case of a young female narcotic addict with Candida albicans endocarditis in whom we diagnosed a large vegetation by 2D echo . Decision for surgery was made solely on the basis of the 2D-echo findings . We feel that 2D-echo findings are reliable in diagnosing fungal endocarditis because, with this technique, the size, shape, mobility, and exact location of the vegetation can be better identified than by the M-mode echo . In addition, early diagnosis of fungal endocarditis helps in treating the patients with medical and surgical therapy which may result in lower mortality.

Circ Shock, 1983, 10(1), 31 - 9
Hepatic and plasma lysosomal enzyme activity in shock-like state following administration of polysaccharide-protein complex isolated from Candida albicans; Kettner M et al.; Polysaccharide-protein complex (PPC) derived from the cell walls of Candida albicans exerts several pathophysiological effects in laboratory animals similar to the symptoms of shock found at acute disseminated candidiasis . The present study evaluated the presumed fragility of hepatic lysosomes in rats in shock-like state following a single dose of PPC (25 mg/kg) administered intravenously, in terms of temporal changes in lysosomal enzymatic activity (cathepsin D, N-acetylglucosaminidase) in four sedimentable fractions and supernatant of liver homogenate after differential centrifugation, as well as in plasma . A reduction of sedimentable lysosomal activity (13,000 X g) was observed during the first hours (3-5 h) after administration of PPC with both lysosomal hydrolases, accompanied by a concomitant increase in the unsedimentable activity that represented the enzymatic activity released from disrupted lysosomes . Plasma levels of cathepsin D and N-acetylgucosaminidase had the same pattern of changes, reaching the maximum level 2-3 h after administration of PPC with a tendency of returning to the control levels by 12 h . Thus PPC from Candida albicans appears to have similar effects upon integrity of hepatic lysosomes as bacterial endotoxins have by labilizing the lysosomal membrane.

J Nutr, 1983 Jan, 113(1), 178 - 83
Dietary ascorbic acid and resistance to experimental renal candidiasis; Rogers TJ et al.; Guinea pigs were maintained for various periods of time on low (0.5 mg/day), intermediate (20 mg/day), or high (100 and 500 mg/day) levels of dietary ascorbic acid . Animals in each experimental group were challenged with Candida albicans via cardiac injection, and the course of infection in the kidneys was assessed . The results show that the animals receiving only 0.5 mg of ascorbic acid per day were significantly more susceptible to the infection than animals maintained on any higher level of dietary ascorbic acid . The greater susceptibility of the guinea pigs in the 0.5-mg level group was evident, however, only during "early" stages of the infection (until about day 3) . Guinea pigs receiving high levels of dietary ascorbic acid were no more resistant at any time after infection, or with any challenge dose, than those receiving an intermediate dietary level . Although these data suggest that vitamin C may be involved in resistance to candidiasis, tissue levels of ascorbic acid do not change significantly with time after infection . These results indicate that low levels of dietary ascorbic acid increase susceptibility to candidiasis, yet high (or "megadose") levels of dietary vitamin C do not show any effect on resistance to this microorganism.

Arzneimittelforschung, 1983, 33(4), 517 - 24
Antimycotic efficacy of bifonazole in vitro and in vivo; Plempel M et al.; The new imadozolyl derivative 1-(p, alpha-diphenyl-benzyl)imidazole (bifonazole, Bay h 4502, Mycospor) shows in vitro the broad spectrum of activity characteristic of azole antimycotics . The intensity of activity under conventional test conditions is equivalent to that of clotrimazole . Further, concentrations of less than or equal to 5 micrograms/ml bifonazole have a fungicidal effect on dermatophytes, and a MIC value of less than or equal to 0.25 micrograms/ml has a maximal effect on Torulopsis glabrata . In ng concentrations bifonazole is effective on proliferating dermatophytes and pseudomycelia of Candida albicans . The resistance situation regarding bifonazole is favourable--as is typical of azole antimycotics . In animal experiments, topical application of concentrations of between 0.05 and 1% bifonazole as a cream or solution are extremely effective on guinea-pig trichophytosis . This is attributed to the therapeutically achievable fungicidal effect on dermatophytes and the long period of time the substance is retained in the skin . The sum of the experimental properties of bifonazole make it possible to recommend the active drug to be applied, once every 24 h, as a 1% cream or solution and the duration of therapy for these indications being reduced to 2-3 weeks.

J Gynecol Obstet Biol Reprod (Paris), 1983, 12(7), 767 - 74
{Benzalkonium chloride tampons . Local tolerance and effects on cervix mucus}; Erny R et al.; Cylinders of soft polyvinyl soaked in benzalkonium chloride have been used as contraceptive tampons . Benzalkonium chloride is a powerful spermicide which belongs to the cationic or saponium detergents . It does not enter the blood stream . These contraceptive sponges are more efficient and better accepted by patients than spermicides used by themselves . One of the principal advantages of the method is to be able to place the tampon in position hours before sexual intercourse . The authors wanted to test if wearing a tampon for a long time did not have an adverse effect on the cervico-vaginal epithelium . 27 women were seen before and after having worn one of these contraceptive tampons for 24 hours: neither the smears nor colposcopy had changed . 21 vaginal biopsies were taken after the tampon had been removed from the area where it had been lying . Vaginal epithelium tolerates the prolonged presence of the sponge well . The authors carried out bacteriological controls before and immediately after removing the tampon 24 hours later . Commensals were still present . Pathogenic sexually transmitted organisms are moderately sensitive to bactericidal action of benzalkonium chloride except for candida albicans, which is resistant . There was no increase in the number of germs in 69 cases studied . The authors carried out scanning electromicroscopy at different magnifications to see the effect on normal cervical mucus at the time of ovulation when it came into contact with benzalkonium chloride . Ovulatory mucus which had been translucent and fluid became thicker and coagulated and the reticulated web took on the appearance of a bunched up web.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemotherapy, 1983, 29(5), 322 - 31
Terconazole - a new broad-spectrum antifungal; Van Cutsem J et al.; Terconazole, a new triazole ketal, is found to be highly active in vitro on a wide range of yeasts and mycelium-forming fungi . The in vitro activity depends largely on the medium used . In vitro it is a potent antifungal agent in preventing the morphogenetic transformation of the yeast into the (pseudo-)mycelium form of Candida albicans . In vivo terconazole is highly active in topical treatment of various experimental models of dermatophytosis and candidosis . It also possesses moderate oral broad-spectrum activity . No side effects were observed.

J Urol (Paris), 1983, 89(9), 695 - 9
{Multiple splenic and renal abscesses caused by Candida albicans: a new diagnostic and therapeutic method using intraoperative echography and closure of the residual cavities with biological glue}; Giannotta A et al.; The Candida albicans infection represents a rather frequent complication in immunodeficient patients, while the evolution towards the growth of multiple intraparenchymal abscesses constitutes a very rare event . The authors describe the diagnostic-therapeutic pathway chosen in a case regarding a young patient in treatment for leukemia , who was affected by multiple splenic and renal abscesses caused by Candida albicans . After a preoperative diagnosis through ultrasonography and C.A.T., a splenectomy was undertaken . Next the only healthy part of the spleen was removed and grafted into the omentum . By using the intraoperative ultrasonography on both kidneys, the abscess cavities were precisely located, aspirated and finally stuck with a human fibrin glue.

Ann Allergy, 1983 Jan, 50(1), 51 - 4
Serum IgE and IgE antibody levels in patients with bronchial asthma, atopic dermatitis, eosinophilic granulomas of the soft tissue (Kimura's disease) and other diseases; Okudaira H et al.; Hyper-IgE immunoglobulinemia was observed in bronchial asthma, atopic dermatitis, eosinophilic granuloma of the soft tissue (Kimura's disease), disseminated visceral eosinophilic granulomas (Zuelzer-Apt syndrome) and disseminated eosinophilic collagen disease, IgE antibodies to environmental allergens (Dermatophagoides farinae mites, Aspergillus fumigatus, mountain cedar pollen, and Candida albicans) were found in bronchial asthma, atopic dermatitis and combinations of the two, but were not significantly detected in the latter three diseases . Hyper-IgE immunoglobulinemia may be divided into two groups on the basis of the presence of specific IgE antibodies directed to environmental allergens . The presence of antimite IgE antibodies in atopic dermatitis sera was confirmed by radioimmunoelectrophoresis . Anti-mite IgE antibodies in atopic dermatitis were heterogeneous in their specificity and the allergenic moieties to which IgE antibodies were directed varied from one case to another.

J Immunol, 1983 Jan, 130(1), 376 - 9
Studies on the cellular nature of Candida albicans-induced suppression; Rivas V et al.; Animals treated with formalinized Candida albicans manifest depressed cellular immune activity . Splenocytes from mice treated with as little as 14 micrograms of this material exhibited significantly reduced responses to the T cell-dependent mitogens phytohemagglutinin and concanavalin A . On the other hand, the B lymphocyte-dependent response to bacterial lipopolysaccharide was normal in these cultures . Splenocytes from treated mice were capable of actively suppressing the T cell- (but not B cell-) dependent proliferative response of normal cells . Analysis of splenocytes from Candida-treated mice showed that the suppressor cell is adherent to glass wool, is not adherent to Sephadex G-10, does not phagocytize carbonyl iron, is not susceptible to treatment with anti-Thy-1 plus C, but does bind specifically to anti-immunoglobulin- (anti-Ig) coated dishes . The adherence to the anti-Ig-coated dishes was not due to the simple attachment of Fc receptor-bearing lymphocytes, because dishes coated with the F(ab')2 fragment of rabbit antimouse IgG bound the suppressor cell . These results suggest that the active Candida-induced suppressor cell is composed, at least in part, of surface Ig-bearing B lymphocytes.

Ann N Y Acad Sci, 1983, 419, 205 - 13
A biochemical study of the phagocytic activities of tuftsin and its analogues; Hisatsune K et al.; The effects of tuftsin and one of its analogues (4 {lys}-tuftsin) on phagocytosis of Staphylococcus aureus and Candida albicans were investigated in mice and rabbits . Mice were intravenously or orally administered 1-25 mg of 4 {lys}-tuftsin per kg daily for 4 to 7 days . After the mice were further treated with cyclophosphamide, they were intravenously challenged with C . albicans . More than 50% of the mice infected with C . albicans were killed within 7 days, although only 20% to 40% of those infected with the same microbes after 4 {lys}-tuftsin treatment died . A combination of 4 {lys}-tuftsin and an antibiotic was found to be somewhat more effective than either one alone . Further, pretreatment with 4 {lys}-tuftsin depressed microbial growth in the kidneys of mice bearing S-180 tumors . Rabbit peritoneal macrophages and polymorphonuclear leukocytes were harvested by intraperitoneal injection of liquid paraffin and of glycogen solution, respectively . For in vitro study of phagocytosis, rabbit macrophages of polymorphonuclear leukocytes were incubated in Hanks solution together with S . aureus and the number of survivors was determined . Enhanced engulfing activity of macrophages and increased bactericidal activity of polymorphonuclear leukocytes were shown by the in vitro phagocytosis experiments . It is expected that 4 {lys}-tuftsin will be effective against infectious disease, especially in immunocompromised hosts such as patients with malignant tumors.

Arch Oral Biol, 1983, 28(5), 415 - 8
Effects of fluoride on locomotion of human blood leucocytes in vitro; Wilkinson PC; The effect of NaF on the locomotion and chemotaxis of human blood neutrophils and monocytes was studied using two assays: the micropore filter assay and a time-lapse cinematographic assay in which the chemotaxis of cells in response to spores of Candida albicans was filmed . At high concentrations (greater than 10(-4) M), NaF inhibited locomotion of both cell types, but no inhibition of locomotion of either cell-type was seen in either assay using NaF at less than or equal to 10(-4) M, whether or not the cells were responding to a chemotactic source . This was so, even for monocytes incubated for 48 h in the presence of NaF . It is therefore improbable that fluoride, at levels added to drinking water or found in the body fluids of persons drinking fluoridated water, has any deleterious effect on the locomotor capacity of phagocytic cells or on their capacity to detect and home on to chemotactic sources.

Cancer Drug Deliv, 1983, 1(1), 37 - 42
Effects of sterols on the therapeutic efficacy of liposomal amphotericin B in murine candidiasis; Lopez-Berestein G et al.; Incorporation of amphotericin B (AMP-B) into phospholipid vesicles (liposomes) has been shown previously to decrease AMP-B toxicity while retaining the antifungal efficacy of the drug . In this report, the role of sterols in the formulation of liposomes as well as in their effectiveness in the treatment of murine candidiasis have been investigated . The presence of ergosterol or cholesterol at different lipid ratios did not augment the encapsulation efficiency of AMP-B as compared with vesicles containing phospholipids alone . There was no significant difference in the survival time of mice infected with Candida albicans treated with sterol-containing vesicles compared with those treated with sterol-free vesicles . These findings suggest that the sterol-free liposomes might be of advantage for delivering AMP-B because of its simple formulation, lack of toxicity, and ease of preparation.

Cell Immunol, 1983 Jan, 75(1), 173 - 80
Resistance and susceptibility to infection in inbred murine strains . II . Variations in the effect of treatment with thymosin fraction 5 on the release of lymphokines in vivo; Neta R et al.; Of nine inbred murine strains sensitized intravenously with killed lyophilized Candida albicans and challenged 3 weeks later with a C . albicans filtrate, four strains were low responders and five were high responders in the in vivo release of migration inhibitory factor (MIF) and gamma interferon (IFN-gamma) . An identical distribution of high- and low-responder strains occurred in response to sensitization with Mycobacterium bovis BCG and subsequent challenge with old tuberculin . Treatment of the murine strains with thymosin fraction 5 prior to sensitization and challenge had different effects: (a) the high-responder strains had a decrease in their release in vivo of the two lymphokines; (b) three of five of the low-responder strains had a striking increase in the in vivo release of MIF and IFN-gamma; and (c) one low-responder strain did not have its response altered . A parallelism existed between the capacity of a murine strain to release the two lymphokines in vivo on stimulation with C . albicans antigens and the capacity of that strain to resist intravenous infection with living C . albicans.

Arch Oral Biol, 1983, 28(12), 1089 - 91
Experimental oral infection of mice with a pathogenic and a non-pathogenic strain of the yeast Candida albicans; Holbrook WP et al.; Oral infection by Candida albicans is thought to be related more to host susceptibility than to virulence of the organism . Using a mouse model of oral candidosis, differences in colonization and infection between two strains of C . albicans were demonstrated.

Arch Dermatol Res, 1983, 275(5), 318 - 23
Experimental studies on the mechanism of benoxaprofen photoreactions; Ljunggren B et al.; Benoxaprofen (BP), a non-steroidal antiphlogistic drug causing skin and nail photoreactions, has been evaluated for photoactivity using three experimental techniques . In vivo in the mouse, BP was phototoxic in doses of 25 mg/kg in combination with UV-A 54J . The phototoxic potency could be confirmed in vitro with the Candida albicans test . In vitro, using photohemolysis, BP showed a dose-dependent activity causing 40% hemolysis at a concentration of about 25 micrograms/ml with UV-A . Also, small UV-B doses caused red cell lysis with a moderate BP concentration . Pre-irradiation experiments showed that UV-A, but not UV-B, photoproducts could account for some of the activity . The action spectrum of BP photoactivity lies mainly in the UV-A, but may also extend into UV-B . Compared with chlorpromazine in vivo and in vitro, and with doxycycline in vivo, BP showed intermediate phototoxic activity.

Acta Microbiol Hung, 1983, 30(1), 25 - 9
The effect of miconazole on ergosterol-less mutant of Candida albicans; Pesti M et al.; The effect of miconazole in fungistatic concentration on an ergosterol-competent Candida albicans strain and its ergosterol-nonproducing mutant was investigated by scanning and transmission electron microscopy . The ergosterol-less mutant showed pronounced alterations by scanning electron microscopy . The increased sensitivity to miconazole of the ergosterol-less mutant was attributed to an altered plasma membrane composition and rigidity.

Z Allg Mikrobiol, 1983, 23(6), 385 - 91
Recombinogenic activity of nalidixic acid for artificial hybrids but not for natural strains of Candida albicans: evidence for the monoploidy of natural strains; Sarachek A; Nalidixic acid induces segregation of auxotrophs from prototrophic hybrids of Candida albicans artifically produced by fusing complementing auxotrophic protoplasts . The auxotrophies recovered are limited to those introduced through the fusion process, and patterns of segregations for linked auxotrophic markers demonstrate the segregants are products mitotic crossing-over . Nalidixic acid does not induce auxotrophies of any sort in clinical isolates of C . albicans . These findings are contrary to a current hypothesis that natural strains of C . albicans are diploid and heterozygous for a variety of auxotrophic mutations.

Z Allg Mikrobiol, 1983, 23(5), 303 - 12
Growth of Candida albicans on artificial D-glucose derivatives; Hrmova M et al.; Growth of Candida albicans on artificial D-glucose derivatives (amino-, methyl-, acylglycosides and N-acetyl-D-glucosamine derivatives) was examined with the aim to find new inducers of the mycelial growth form . For representatives of particular groups (alpha-D-glucopyranosylamine, D-glucose and N-acetyl-D-glucosamine) some physiological (growth, doubling time, specific growth rate, oxygen uptake and CO2 production, respiration quotients), biochemical (dry weight yield, protein content, ethanol production), and morphological parameters (length-width quotient, volume, percentage of budding cells) of cultures in different growth phases were determined with regard to the type and concentration of carbon source . The results obtained may be valuable for studies of the structure-utilization relationships of carbohydrate derivatives as well as for the elucidation of yeast-mycelial transition in Candida albicans induced by unphysiological hexoses degradable intracellularly.

Scand J Rheumatol, 1983, 12(3), 249 - 53
IgA antibodies to Klebsiella pneumoniae in ankylosing spondylitis; Trull AK et al.; Serum IgA antibodies to Klebsiella pneumoniae were measured in 65 patients with ankylosing spondylitis (AS) during different phases of disease activity and compared with the antibody level in 21 psoriatic arthritis (PsA) patients, 43 rheumatoid arthritis (RA) patients and 57 healthy controls . The mean IgA antibody to Klebsiella in AS patients with an erythrocyte sedimentation rate (ESR) greater than or equal to 15 mm/h was significantly higher than the antibody level in patients with an ESR less than 15 mm/h (p less than 0.02) and tended to increase with rising ESR . There was a significant difference in anti-Klebsiella antibody levels between AS patients with an elevated ESR and antibody levels in PsA patients (p less than 0.001), RA patients (p less than 0.001) and healthy controls (p less than 0.005) . There was no difference between healthy controls and patients with PsA, RA or AS patients with a low ESR . The IgA anti-Klebsiella antibody was specifically absorbed out from sera with inactivated klebsiella pneumoniae organisms . Antibody levels to Candida albicans and Escherichia coli did not differ in patients vis-a-vis control subjects . The mean serum anti-Klebsiella IgA level was found to be higher in patients who were either clinically active or had positive faeval cultures, when compared with patients with inactive disease and negative cultures, but these differences were not statistically significant, although when both parameters were examined together a significant additive effect was detected (p less than 0.001) . It is concluded that patient with AS exhibit a specific elevation of serum IgA antibody to Klebsiella antigen.

Microbios, 1983, 37(148), 105 - 15
Growth and acid production of Candida albicans in carbohydrate supplemented media; Samaranayake LP et al.; Aerobic and anaerobic growth characteristics and acid production of a clinical and a reference laboratory strain of Candida albicans in 0.1 M, glucose or sucrose-supplemented batch cultures were examined for 72 h, at 37 degrees C . Both strains gave sigmoid growth curves, aerobically, and the pH dropped from 7.0 to 3.5 in 48 h . Candidal growth or acid production was not observed in submerged, anaerobic cultures . The specific growth rate (mu) of the clinical strain of Candida was significantly greater than the reference strain, in both sugar media . The major acidic component initiating and sustaining the pH drop appeared to be acetate, although formate, pyruvate and propionate were detected in varying proportions in glucose or sucrose cultures . These anionic, acidic metabolites of C . albicans, may play a role in the pathogenesis of mucosal candidoses such as chronic atrophic candidosis.

Microbios, 1983, 37(147), 23 - 8
Effect of butylated hydroxyanisole on the antifungal activity of amphotericin B; Cosgrove RF; Monitoring the growth curves of Candida albicans has shown that in the presence of sub-MIC levels of amphotericin B the lag phase is extended . If butylated hydroxyanisole (BHA) is added prior to, or with the amphotericin B the lag phase is extended further . However, if BHA is added after the antibiotic, the growth curve is identical to that produced in the presence of amphotericin B alone . The effect of BHA was found to follow the kinetics of a zero order reaction, and adsorption data for amphotericin B to yeast cells shows that BHA may occupy sites in the cell wall of the organism normally occupied by amphotericin B . It is suggested that if the polyene binding capacity in the cell wall is satisfied by the BHA, then the effective concentration of amphotericin B available to exert its lethal effect on the sterol in the cell membrane is increased.

Arzneimittelforschung, 1983, 33(4), 538 - 45
Microscopic studies of Candida albicans and Torulopsis glabrata after in vitro treatment with bifonazole . Freeze fracture electron microscopy; Barug D et al.; 1-{(4-Biphenylyl)-phenylmethyl}-1H-imidazole (bifonazole, Bay h 4502, Mycospor) induced profound ultrastructural alterations in Candida albicans and Torulopsis glabrata as observed by freeze fracture electron microscopy . These alterations were characterized by (1) deformation and decrease in number of invaginations in the protoplasmic fracture face and corresponding ridges on the exoplasmic fracture face, and (2) separation of the plasma membrane from the cell wall, leaving a gap which frequently contained small vesicles . Moreover, parts of the inner half of the plasma membrane of C . albicans cells had been torn off and adhered to the exoplasmic fracture face . Cross-fractures of bifonazole-treated cells of C . albicans showed swollen mitochondria and deposition of lipid granules.

Arzneimittelforschung, 1983, 33(4), 528 - 37
Microscopic studies of Candida albicans and Torulopsis glabrata after in vitro treatment with bifonazole . Light and scanning electron microscopy; Barug D et al.; 1-{(4-Biphenylyl)-phenylmethyl}-1H-imidazole (bifonazole, Bay h 4502, Mycospor) preferentially inhibited yeast-hypha conversion in the dimorphic fungus Candida albicans . As observed by phase-contrast and scanning electron microscopy the morphology of C . albicans yeast cells and Torulopsis glabrata cells markedly altered after treatment with bifonazole . Whereas control cells were mostly occurring singly, the bifonazole-treated cells did not separate, resulting in the formation of chains and clusters of interconnected cells . Furthermore, in contrast with control cells bifonazole-treated cells of C . albicans and T . glabrata were almost spherical in shape . Evidence is presented by means of fluorescence microscopy that bifonazole-treated yeast cells of C . albicans frequently lacked septa and often contained irregular deposition of chitin.

Int J Tissue React, 1983, 5(1), 73 - 84
Comparison between natural reactivity (NR) against Candida albicans and natural killer (NK) activity against YAC-1 tumour cells; Bistoni F et al.; Cytotoxic activity against Candida albicans was measured in vitro in a 4-h 51Cr-release assay . The levels of reactivity correlated well with the number of polymorphonuclear cells in the effector population, being augmented by the enrichment of polymorphonuclear granulocytes . To exclude the possible role of contaminating natural killer cells, natural killer activity against tumour cells was compared with natural reactivity against Candida albicans in vitro . The findings indicate that there are many differences between these reactivities including organ and strain distribution, age dependency, adherence to nylon, and susceptibility to modulation by immuno-adjuvants and to treatment with anti-Thy 1.2 antiserum plus complement . These data further define in vitro polymorphonucleate-mediated cytotoxicity against Candida albicans on the basis of the above-mentioned criteria and clearly demonstrate that this in vitro reactivity could not be due to the presence of contaminating natural killer cells in the effector cell population.

Z Naturforsch {C}, 1983 Jan-Feb, 38(1-2), 151 - 2
Antimicrobial activity of N,N'-bis(decylmethyl)-alpha,omega-alkanediamine dioxides {1}; Devinsky F et al.; Antimicrobial activity of N,N'-bis(decylmethyl)-alpha,omega-alkanediamine dioxides determined on Staphylococcus aureus, Escherichia coli, and Candida albicans is presented as minimal inhibitory concentration (MIC) . The effect of the length of linking alkylene chain on this activity has been followed.

Antimicrob Agents Chemother, 1983 Jan, 23(1), 79 - 85
Mechanisms of action of 5-fluorocytosine; Waldorf AR et al.; 5-Fluorouracil and 5-fluorodeoxyuridine monophosphate levels were estimated in 75 isolates of Candida albicans to determine whether 5-fluorocytosine susceptibility could be ideally correlated with the intrafungal formation of both 5-fluorodeoxyuridine monophosphate and 5-fluorouridine triphosphate or a reciprocal formation of the two metabolites to prove the mechanism of 5-fluorocytosine activity . Using the results of four in vitro susceptibility tests, we separated isolates of C . albicans into susceptibility groups . For most strains, there was a positive correlation between the degree of 5-fluorocytosine susceptibility and the inhibition of biosynthesis of both RNA and DNA, incorporation of 5-fluorouracil into RNA, inhibition of ribosomal protein synthesis, and levels of 5-fluorodeoxyuridine monophosphate . However, in some strains with a similar degree of 5-fluorocytosine resistance, either reduced incorporation of 5-fluorouracil or reduced 5-fluorodeoxyuridine monophosphate levels occurred, suggesting that these two mechanisms are not necessarily linked to each other and that both may be responsible for 5-fluorocytosine activity.

Infect Immun, 1983 Jan, 39(1), 172 - 8
Protective effect of a muramyl dipeptide analog encapsulated in or mixed with liposomes against Candida albicans infection; Fraser-Smith EB et al.; Encapsulation of N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine in multilamellar vesicles composed of phosphatidylcholine, cholesterol, and phosphatidylserine (7:6.7:3) or phosphatidylcholine and phosphatidylserine (7:3) reduced the amount of drug needed to protect against a Candida albicans intravenous infection . The 50% effective doses for encapsulated and free drug were 5.5 and greater than 80 mg/kg, respectively . The optimum treatment was twice (at days 4 and 2 preinfection) by the intravenous route . Intraperitoneal, subcutaneous, and oral routes of administration were ineffective . The same potentiation of anti-Candida activity was observed whether the lower dose of drug was encapsulated in multilamellar vesicles, mixed with multilamellar vesicles, or given either 1 h before or 1 h after multilamellar vesicles . It was postulated that the mechanism of action involved the retention of the liposomes by organs of the reticuloendothelial system, resulting in an enhanced response of the macrophages to the immunostimulating activity of the N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine given in conjunction with the vesicles.

Br J Dermatol, 1983 Jan, 108(1), 69 - 76
Class-specific antibodies in young and aged humans against organisms producing superficial fungal infections; Sohnle PG et al.; Class-specific antibodies (IgG, IgA and IgM) against Candida albicans, Pityrosporum orbiculare and Trichophyton rubrum were measured in the serum from twenty-one young subjects (aged 23-44) and twenty elderly subjects (aged 70-88) who did not have a history of significant superficial fungal infections . We found that (a) antibody to all three organisms was present in all subjects in both groups, (b) except for a reduced level of IgM antibody against P . orbiculare, the elderly subjects demonstrated humoral responses in these assays similar to those of the young subjects, (c) IgA antibody was present in higher amounts against C . albicans that against P . orbiculare or T . rubrum in both groups, and (d) the proportion of IgM antibody against T . rubrum was higher than that against the other two organisms . These findings suggest that the ecology of these three organisms with respect to the normal human host may be reflected in the serological responses against them.

Am Rev Respir Dis, 1983 Jan, 127(1), 110 - 2
Murine pulmonary macrophages: evaluation of lung lavage fluids, miniaturized monolayers, and candidacidal activity; Sugar AM et al.; Optimal yields of pulmonary macrophages (PuM) from lavage of normal murine lungs have been obtained by the study of several different lung lavage fluids . Approximately 1 X 10(6) PuM can be consistently recovered from mice weighing 20 to 30 g, using 15 ml of phosphate buffered saline with 0.1% EDTA, with or without 10% fetal calf serum at 37 degrees C . Use of Terasaki tray wells for monolayer formation has allowed a relatively small number of cells (75,000) to be used to prepare multiple replicate wells from each mouse . Simultaneous functional comparisons with other cell types, e.g., peritoneal macrophages (PeM) were performed using this practical and economical system . Data on the phagocytosis and killing of Candida albicans by PuM and PeM are presented as evidence of the utility of this miniaturized system.

Boll Ist Sieroter Milan, 1983, 62(6), 531 - 4
In vitro effect of ketoconazole on human neutrophil chemotaxis and Candida albicans killing; Le Moli S et al.; Ketoconazole, an antifungal agent, was investigated to discover its possible enhancing role on polymorphonuclear chemotactic and Candida killing functions in vitro . Polymorphonuclear leukocytes from 10 healthy subjects and two different strains of Candida albicans were used . At concentrations of 1 microgram/ml Ketoconazole showed no distinct synergistic effect on either of the above-mentioned polymorphonuclear cellular functions, but, on the other hand it operated directly on Candida cells . In addition, this drug did not demonstrate any chemotactic activity on granulocytes . These data could suggest that host cellular defence and Ketoconazole exert parallel rather than synergistic activity.

Eur J Cancer Clin Oncol, 1983 Jan, 19(1), 43 - 8
Oral prophylaxis with miconazole or ketoconazole of invasive fungal disease in neutropenic cancer patients; Meunier-Carpentier F et al.; Ketoconazole or miconazole was randomly administered to 42 and 46 neutropenic patients respectively . Of the total number of stool cultures 12% were positive for yeasts in both groups; 4% of the total number of cultures from other sites (nose, throat, skin) were positive in both groups . Candida albicans was the most common isolate, but other fungal species were also identified . No patient developed fungemia; 5/88 patients developed severe oropharyngeal candidiasis while receiving prophylaxis . Among the 21 autopsies performed, 5 cases of pulmonary aspergillosis and 2 local and 1 disseminated candidiasis were demonstrated in 7 patients . Although there was no placebo group of patients in this study, post-mortem data suggest that miconazole or ketoconazole might reduce the incidence of disseminated candidiases in neutropenic patients.

Antimicrob Agents Chemother, 1983 Jan, 23(1), 185 - 7
Effect of ketoconazole on the fungicidal action of amphotericin B in Candida albicans; Sud IJ et al.; Amphotericin B-susceptible Candida albicans became resistant to the drug after growth in the presence of ketoconazole . Chromatographic analysis of cellular sterols showed that the organisms became depleted of ergosterol in parallel with the development of amphotericin B resistance . The implications of these findings are discussed in relation to combination chemotherapy with these two important antifungal agents.

Immunol Lett, 1983 Jan, 6(1), 7 - 11
The effect of oligopeptides on the C3b receptor-mediated functions of rat macrophages; Foris G et al.; Effects of various substances known to influence macrophage functions on the adherence of C3b-coated sheep erythrocytes (E-C3b) and their phagocytosis by elicited rat peritoneal macrophages (PM) has been studied . Different oligopeptides (OP) having a chemotactic effect, such as tuftsin, angiotensin II (At II) and the OP-fraction of a lymphokine preparation (LK-OP) increased both adherence and phagocytosis of E-C3b in a concentration-dependent fashion . In contrast, neither substances influencing the membrane cation transport nor prostaglandins (PG) and cyclic nucleotides significantly changed the C3b receptor (C3bR)-dependent effector functions of macrophages . Enhanced functions of the C3bR were not associated with an increased capability of PMs for intracellular killing of Candida albicans.

Cell Immunol, 1983 Jan, 75(1), 160 - 72
Resistance and susceptibility to infection in inbred murine strains . I . Variations in the response to thymic hormones in mice infected with Candida albicans; Salvin SB et al.; Nine inbred murine strains were either highly resistant or highly susceptible to intravenous challenge with 4 X 10(4) to 1 X 10(5) cells of Candida albicans . The resistant strains had the capacity to develop delayed footpad reactions on appropriate sensitization and challenge; the susceptible strains did not have this innate capacity . Administration of thymosin fraction 5 beginning on the day of infection greatly increased the resistance of the susceptible strains to infection, but decreased the resistance of the resistant strains . In contrast, thymosin fraction 5 enhanced the delayed footpad responses of resistant-sensitized mice to specific antigen, but did not have a detectable effect on the delayed footpad reactions of the susceptible strains . Reinfection of the two types of strains had different effects, in that, depending on the strain, resistance could be increased, decreased, or not influenced at all.

Microbios, 1983, 38(153-154), 177 - 85
An investigation of the factors involved in increased adherence of C . albicans to epithelial cells mediated by E . coli; Makrides HC et al.; An in vitro study was carried out in order to investigate the effect of Escherichia coli on the adherence of Candida albicans to epithelial cells . Pre-incubation of HeLa cell monolayers with E . coli cell suspensions resulted in a large, significant increase in candidal adherence . Similar increases in adherence to HeLa cells were observed when incubation of C . albicans and HeLa cell monolayers was carried out in the presence of a mannose-specific lectin, concanavalin A . The enhanced adhesion of C . albicans due to both E . coli and concanavalin A was significantly reduced in the presence of mannose and alpha-methyl-D-mannoside although both sugars alone significantly increased candidal adherence . These studies indicate that the increased candidal adherence due to the presence of E . coli is mediated by the presence of fimbriae on the bacterial cells and mannose-like receptors on both the surfaces of C . albicans and the epithelial cells.

Biochem Int, 1983 Jan, 6(1), 119 - 28
Why choline supplementation did not enhance phosphatidylcholine level in Candida albicans; Trivedi A et al.; In contrast to Saccharomyces cerevisiae cells, the supplementation of the growth media of Candida albicans cells with choline did not result in PC enrichment . The level of accumulation of choline uptake, which is the first step of its utilisation was found to be 50% higher in S . cerevisiae cells . However, the activity of choline kinase (EC 2.7.1.32), the first enzyme in CDP-choline pathway was identical between the two cell types . It appears that CTP: phosphocholine cytidylyl-transferase (EC 2.7.7.15) may be the regulatory enzymatic step in overall PC biosynthesis of C . albicans cells.

Quad Sclavo Diagn, 1982 Dec, 18(4), 406 - 15
{Identification of yeast-like fungi in the hospital laboratory}; Crotti D et al.; Although Candida albicans is a major pathogen yeast, various similar species and genus are responsible for illness in human beings . Therefore, it is necessary to find a practical and efficient system for the identification of these pathogenic microorganisms . The authors propose a valid scheme for this purpose.

J Reticuloendothel Soc, 1982 Dec, 32(6), 443 - 8
Depressed human monocyte function after influenza infection in vitro; Gardner ID et al.; Human monocytes were separated from peripheral blood of 22 normal healthy adults and incubated with Hsw1N1 influenza virus or diluted allantoic fluid . The treated monocyte populations were tested for five parameters of monocyte function . Influenza infection markedly inhibited the monocyte chemotactic response and the killing of Candida albicans; infection also depressed phagocytosis, slightly reduced spreading, but did not affect adhesion to glass . These results suggest that influenza virus may also have an inhibitory effect on monocyte function in vivo and help to explain the increased susceptibility to secondary bacterial infection and the general immunosuppression seen in influenza infection.

Hautarzt, 1982 Dec, 33(12), 632 - 5
{Development and current status of the serodiagnosis of candidiasis}; Muller HL; Present day knowledge of the antigen structure of Blastomyces and the availability of sensitive analytic methods have made serology a valuable aid in the diagnosis of candidiasis . Several factors are essential for correct interpretation: knowledge of the normal titer values obtained by the chosen method, or even better, when supervising patients at risk of mycosis, knowledge of the individual titer; monitoring titer fluctuation and the judicious combination of different methods . The use of Candida albicans as antigen source permits detection of the most common forms of candidiasis . In infections caused by C . krusei, C . pseudotropicalis, and C . guilliermondii, however, homologous antigens must be used to detect the antibodies . Serologic differentiation of mucosal from systemic mycosis is facilitated by detection of antibodies against the cell protein of the blastomycetes.

Sabouraudia, 1982 Dec, 20(4), 313 - 23
A comparison of bifonazole (BAY H 4502) with clotrimazole in vitro; Shadomy S et al.; The antifungal activity of a new topical imidazole, bifonazole (BAY h 4502, Bayer AG Institute for Chemotherapy), was compared in vitro with that of clotrimazole (BAY b 5097, Schering Corporation) in tests with 67 pathogenic and commensal yeasts, 45 dermatophytes and 14 miscellaneous pathogenic fungi by an agar dilution method . Three media, Kimmig's agar, Sabouraud's agar, and casein-yeast extract-glucose agar were used . Bifonazole was inhibitory for nearly all the yeasts tested including Candida albicans, C . parapsilosis, and Torulopsis glabrata with geometric mean minimal inhibitory concentrations (G-MIC) averaging 5 micrograms ml-1 on all three media . Clotrimazole was the more active drug against these same species with G-MIC's ranging from 0 . 25 to 2 . 10 micrograms ml-1 . Results with bifonazole were affected by choice of medium with Kimmig's agar generally giving the lowest MIC's; results with clotrimazole were also affected by choice of medium but to a lesser degree . In nearly all instances, both bifonazole and clotrimazole were inhibitory for the dermatophytic fungi at concentrations of 0 . 50 micrograms ml-1 or less and clotrimazole was the more active drug . Choice of medium was, in general, not a factor with these latter fungi which included Epidermophyton, Trichophyton, and Microsporum species . Both drugs were active against species of Aspergillus (G-MIC's of 3 . 18 micrograms ml-1), Fusarium (G-MIC's ranging from 1 . 59 to 12 . 70 micrograms ml-1) and Scopulariopsis (G-MIC's of 1 . 78 micrograms ml-1); clotrimazole was the more active drug by factors of 2- to 4-fold on all three media . Bifonazole MICs were shown to vary with pH (maximal activity at pH 6 . 5) with selected yeasts when tested on Kimmig's agar . Differences in results obtained with varying inoculum sizes for these same yeasts generally were unremarkable . With selected species of yeasts and dermatophytes, it was determined that the ratio of minimal fungicidal to inhibitory concentrations (MFC/MIC) was much lower for bifonazole than for clotrimazole.

Infect Immun, 1982 Dec, 38(3), 921 - 4
Synergistic effect of Candida albicans and Staphylococcus aureus on mouse mortality; Carlson E; A synergistic effect on mouse mortality was demonstrated in combined infection of mice with Candida albicans and a Staphylococcus aureus strain isolated from a patient with toxic shock syndrome . Mice exhibited high resistance when inoculated intraperitoneally by either pathogen alone . Dual infection with the two organisms together, however, at doses which separately caused no animal deaths, resulted in 100% mortality . This synergistic effect could not be reproduced when either of the agents was heat inactivated.

Int J Lepr Other Mycobact Dis, 1982 Dec, 50(4), 455 - 67
In vitro lymphocyte stimulation in patients with lepromatous and borderline tuberculoid leprosy . The effect of dapsone treatment on the response to Mycobacterium leprae antigens, tuberculin purified protein derivative and non-mycobacterial stimulants; Reitan LJ et al.; Lymphocytes from peripheral blood were isolated from leprosy patients and healthy contacts (HC) of leprosy patients and stimulated in vitro with: Mycobacterium leprae and a M . leprae cell wall antigen, MLW 1; tuberculin purified protein derivative (PPD); antigens prepared from Candida albicans, Entamoeba histolytica, Leishmania aethiopica, and parotitis virus; the non-specific mitogens phytohemagglutinin (PHA) and concanavalin A (Con-A) . Lymphocytes from patients with untreated lepromatous leprosy failed to respond to the M . leprae antigens, and the median response to PPD was also significantly (p less than 0.005) lower than in the HC group . They responded almost as well as the other groups to non-mycobacterial antigens, PHA, and Con-A . In LL patients who had been treated with dapsone for several (median 10) years, the failure to respond to M . leprae antigens remained, but the depression of the PPD response and the slight non-specific depression of the lymphocyte stimulation test (LST) responsiveness had been reversed . Our results confirm that the major defect in the cell-mediated immune response of LL patients is M . leprae-specific and permanent . The possibility that the defect may be due to a continuous, antigen-induced suppression of the immune response is discussed . That the defect also affected the response to PPD is important since it points to a clear antigenic relationship between M . leprae and BCG/M . tuberculosis . Evidence is presented suggesting that an antigen induced suppressor mechanism may be operating in vitro with cells from patients with borderline tuberculoid leprosy.

Br J Oral Surg, 1982 Dec, 20(4), 294 - 8
Nystatin-resistance of candida albicans isolates from two cases of oral candidiasis; Martin MV et al.; Two cases of oral candidiasis are described which failed to respond to nystatin therapy when used in combination with triamcinolone acetonide . The isolates of C . albicans obtained from the patients after treatment showed high in vitro resistance to nystatin when tested in combination with triamcinolone acetonide . Triamcinolone acetonide was detected in the saliva of both patients after treatment . Addition of this saliva to the isolates of C . albicans obtained after treatment was found to confer nystatin resistance . Both patients were treated with miconazole nitrate and a mycological and clinical cure was obtained in one of the cases.

Sabouraudia, 1982 Dec, 20(4), 303 - 11
Effects of amphotericin B and its methyl ester on plasma membranes of Candida albicans and erythrocytes as examined by freeze-fracture electron microscopy; Sekiya T et al.; Freeze-fracture electron microscopy of the plasma membranes of Candida albicans yeast cells and red blood cells treated with amphotericin methyl ester and amphotericin B showed that amphotericin B (50 micrograms ml-1) caused extreme aggregation of intramembranous particles on the protoplasmic fracture face of the C . albicans membrane, and a marked reduction of the density of intramembranous particles . On the other hand, the rearrangement of intramembranous particles induced by amphotericin methyl ester (50 micrograms ml-1) produced elevations of the particle-free membrane domains toward the outside of the cells, so that the particles were aggregated in linear furrows surrounding these elevations on the protoplasmic fracture face, and the corresponding ridges on the exoplasmic fracture face . The density of intramembranous particles was greatly reduced on the protoplasmic fracture face . Both polyenes produced only small changes in the erythrocyte membranes at the same concentration . These results suggest that amphotericin methyl ester affects the ergosterol-containing membranes more than amphotericin B, and that ergosterol has a higher sensitivity for these two polyene antibiotics than cholesterol.

J Bacteriol, 1982 Dec, 152(3), 969 - 75
Recombination analysis of naturally diploid Candida albicans; Poulter R et al.; A multiply auxotrophic strain, hOG45, was derived from Candida albicans ATCC 10261 . Prototrophic revertants of this multiple auxotroph were selected after mutagenesis . These prototrophic revertants were distinguishable from the original prototroph, ATCC 10261, because of their mitotic instability . They gave rise to auxotrophic derivatives which displayed one or more of the auxotrophic requirements characteristic of hOG45 . Two of the auxotrophic requirements, those for adenine and methionine, frequently reappeared together in the auxotrophic derivatives of the prototrophic revertants . This apparent linkage of ade and met was confirmed by protoplast fusion analysis of the original auxotroph . These data indicate that C . albicans ATCC 10261 is diploid, the multiple auxotroph h0G45 is homozygous for recessive auxotrophic alleles, the prototrophic revertants are multiple heterozygotes, the auxotrophic derivatives are homozygotes produced by mitotic crossing-over, and the association between the ade and met alleles is due to linkage.

Int J Pediatr Nephrol, 1982 Dec, 3(4), 287 - 91
Candida peritonitis in children on continuous ambulatory peritoneal dialysis; Hogg RJ et al.; The management, complications and outcome of two small children who developed Candida albicans peritonitis are reported . Both children developed peritonitis while on continuous ambulatory peritoneal dialysis (CAPD) but their fungal infections were treated differently . In one patient, Amphotericin B (1-4 micrograms/ml) was added to the dialysate; infection resolved but an extensive fibrous reaction developed in the peritoneal cavity making subsequent CAPD ineffective . The second patient was treated with a recently introduced oral antifungal agent, Ketoconazole; her catheter was removed . This patient recovered without any identifiable side effects of the drug . This report discusses the clinical course of two different approaches to Candida peritonitis and suggests certain recommendations regarding the treatment of this uncommon, but potentially lethal complication of CAPD.

J Am Vet Med Assoc, 1982 Dec 1, 181(11), 1316 - 21
Candidiasis in captive cetaceans; Dunn JL et al.; Disseminated Candida albicans infections were found or suspected in 4 captive cetaceans . Ketoconazole at a dosage of 2.5 mg/kg, BID, administered orally for 18 days, followed by 8 biweekly oral doses of levamisole hydrochloride at the rate of 9 mg/kg, resulted in regression of clinical signs of candidiasis in an adult male Atlantic bottlenose dolphin (Tursiops truncatus) . A higher dosage of ketoconazole (6 mg/kg, BID) was effective in eliminating the shedding of C albicans from an adult male belukha whale (Delphinapterus leucas) . A juvenile female harbor porpoise (Phocoena phocoena) treated with nystatin died with disseminated candidiasis, as did a juvenile male longfinned pilot whale (Globicephala melaena) treated with nystatin and levamisole . Three other adult bottlenose dolphins, a juvenile female belukha whale, and a female Commerson's dolphin (Cephalorhynchus commersonii) kept in the same water system never had evidence of candidiasis . A 5th bottlenose dolphin (an adult female) was culture-positive on 1 occasion, but never had signs of the disease.

Infect Immun, 1982 Dec, 38(3), 1102 - 8
Enhanced antibody responses induced by Candida albicans in mice; Cutler JE et al.; Candida albicans may immunopotentiate antibody responses in mice to antigens unrelated to the fungus . This effect occurred best with cell-associated, rather than soluble, antigens . When dead yeasts, cell walls, or a water-soluble candidal polysaccharide were used, immunopotentiation was most dramatic when the antigen and fungal materials were given concomitantly via an intraperitoneal injection . However, mice infected with viable yeasts several days before antigen administration also developed heightened responses to the antigen . The mechanism of the C . albicans-induced adjuvanticity was not defined, but the effect seemed to correlate with induction of inflammation . The presence of C . albicans or other inflammatory agents in the peritoneal cavity caused a more rapid uptake of particulate antigen by the liver . The relationship between this event and immunopotentiation is not known . These studies demonstrate that C . albicans may have profound effects on host immune responses . Because immunological aberrations are commonly found in patients with candidiasis it may be important to determine whether some of these aberrations result from, rather than precede candidiasis.

Farmaco {Sci}, 1982 Nov, 37(11), 759 - 63
{Antifungal activity of diesters of 2-mercaptobenzene methanethiol}; Montanari L et al.; Some diesters of 2-mercaptobenzenmethanthiol and of 2-(2-nitrophenyl)-1,3-benzodithiyne were prepared and tested for in vitro antifungal activity . The substances {Table I: substances (I leads to VIII)} were obtained by condensation of 2-mercaptobenzenmethanthiol with suitable reagents . The antifungal activity of the products was tested in vitro against the following strains: Candida albicans, Saccharomyces cerevisiae and Trichophyton mentagrophytes . It was found that antimycotic activity is shown by only some of the diesters of 2-mercaptobenzenmethanthiol with acyl alkylthiocarbamic groups (Table I) . The diesters with aliphatic, aromatic, alkylcarbamic groups and the 2-(2-nitrophenyl)-1,3-benzodithiyne are inactive or only slightly active.

Int Ophthalmol, 1982 Nov, 5(3), 175 - 9
Mycolase II: an enzyme antifungal agent interacts with the polyene antibiotic pimaricin in the treatment of keratomycosis; Oji EO; An animal model of keratomycosis was used to study the interaction between the new enzyme antifungal compound mycolase II and the polyene antifungal antibiotic pimaricin . Well established corneal infection caused by an ocular pathogenic candida albicans on New Zealand white male rabbits were treated with 3% mycolase II, 5% pimaricin and a combination of 3% mycolase II and 5% pimaricin respectively . The rates of resolution of the corneal lesions for each group of eyes treated by the various drugs were determined and the results were analysed by computer using a two-way analysis of variance to determine the interaction or independence of 3% mycolase II in combination therapy with 5% pimaricin in rabbit keratomycosis . The analysis of variance showed a significant level of positive interaction after each period of treatment . (P less than 0.001).

Infect Control, 1982 Nov-Dec, 3(6), 471 - 4
Transient and resident microflora of burn unit personnel and its influence on burn wound sepsis; Heggers JP et al.; The exogenous contamination of a thermally injured patient by contact with the health are team has been a major concern of all burn units . Since the University of Chicago Burn Center routinely monitors each burn injury for sepsis by quantitative bacteriology and recently examined the microbial population present on the hands of the health care team, it was felt that these combined data would shed some pertinent information on exogenous burn wound sepsis . Twenty-nine patients with clinical burn wound sepsis and a bacterial level of greater than 10(5) bacteria/gram of tissue were studied . These patients yielded a variety of microorganisms with P . aeruginosa and Staphylococcus aureus being predominant, followed in incidence by Candida albicans . The resident and transient microflora isolated from each member of the health care team treating the specific individual concerned did not correlate with the causative agent of burn wound sepsis . The most frequent isolate from the staff personnel was Staphylococcus epidermidis followed by Micrococcus species . Though colonization of the thermally injured individual has been reported, these data strongly suggest that colonization is primarily one of an endogenous source rather than that of an exogenous one.

Bull Soc Pathol Exot Filiales, 1982 Nov, 75(5), 476 - 83
{Phagocytosis of Candida albicans by polymorphonuclear leucocytes from patients with nodular lepromatous leprosy}; Ramos-Zepeda R et al.; Patients suffering from nodular lepromatous leprosy are deficient in cellular immunity but may not be more susceptible to other infections . Therefore it is possible that other defense mechanisms are operational in dealing with other infectious agents these patients may be exposed to . In this report, the phagocytic and fungicidal activity of polymorphonuclear (PMN) cells against Candida albicans was examined using PMN from 20 nodular lepromatous patients and from 20 healthy subjects (controls) . The method used was that of PMN adherence to glass . The phagocytic activity was evaluated after 15 mn and 45 mn . We observed that there was phagocytized by 94 % of the PMN from patients and by 95 % of the PMN from the controls . The phagocytic index of the yeasts ingested by the PMN were 4.47 and 4.10 for, respectively, patients and controls . The frequencies of yeasts killed by PMN from patients and controls were, respectively, 29.6 and 29.4 % . The results indicated that PMN from patients and healthy controls had the same capacity to phagocytize and to destroy yeasts of C . albicans.

Ann Microbiol (Paris), 1982 Nov-Dec, 133(3), 491 - 501
{Comparative effect of a single or continuous administration of "Saccharomyces boulardii" on the establishment of various strains of "candida" in the digestive tract of gnotobiotic mice}; Ducluzeau R et al.; Saccharomyces boulardii became established in the digestive tract of monoxenic mice; the number of viable cells ranged around 10(7.5) per gram faeces . This yeast was drastically eliminated from the digestive tract of gnotoxenic mice harbouring a complex flora of human origin . In monoxenic mice harbouring S . boulardii, Candida albicans became established at a level equivalent to that observed in monoxenic mice harbouring C . albicans alone . If gnotoxenic mice received a concentrated suspension of viable S . boulardii cells so as to steadily maintain a population level close to 10(9) viable cells, C . albicans then became established at a level 10 to 50 times lower than that reached by the yeast strain alone . The antagonistic effect exerted in vivo by S . boulardii was preventive and curative . It was active against C . albicans, C . krusei and C . pseudotropicalis strains, but ineffective against C . tropicalis . This antagonistic effect disappeared when S . boulardii cells were killed by heating.

Antimicrob Agents Chemother, 1982 Nov, 22(5), 810 - 5
Candida albicans resistance to 5-fluorocytosine: frequency of partially resistant strains among clinical isolates; Defever KS et al.; Resistance to 5-fluorocytosine was studied in 137 independent Candida albicans clinical isolates . Seventy-eight isolates (57%) were susceptible; 51 isolates (37%) were partially resistant; 8 isolates (6%) were highly resistant . All partially resistant isolates gave rise to variants which were highly resistant . Some susceptible isolates gave rise to variants which were highly resistant; two such isolates were shown to be heterozygous for resistance, and these isolates define a new type of heterozygote . A partially resistant isolate gave rise to resistant variants which were auxotrophic for lysine; this result was interpreted as preliminary evidence that the allele which determined resistance was linked to an allele which determined auxotrophy for lysine . It is suggested that heterozygotes constitute a source of preexisting mutant alleles which determine resistance, and that 5-fluorocytosine treatment of infections due to heterozygotes may result in significant selection for resistant variants . A simple screening procedure is described by which partially resistant strains may be recognized.

J Med Microbiol, 1982 Nov, 15(4), 511 - 7
The effect of dietary carbohydrates on the in-vitro adhesion of Candida albicans to epithelial cells; Samaranayake LP et al.; The effects of dietary carbohydrates on the adherence of Candida albicans to HeLa epithelial monolayers and buccal epithelial cells were compared by two assay systems . Candida preincubated in 0.5M, glucose, sucrose, galactose, xylitol or maltose medium produced a significant enhancement in adhesion to both types of epithelial cells . Maltose was the most effective sugar and glucose the least effective in promoting adhesion, while lactose had no significant effect . A clinical isolate of C . albicans demonstrated a greater overall enhancement in adhesion from preincubation with glucose, sucrose and maltose, when compared with a reference laboratory strain of Candida . These results imply that exogenous or endogenous carbon sources may affect the oral and vaginal carriage of C . albicans, by modifying their adhesive properties.

Infect Immun, 1982 Nov, 38(2), 788 - 90
Mammary gland contamination as a means of establishing long-term gastrointestinal colonization of infant mice with Candida albicans; Hector RF et al.; Infant outbred CD-1 mice were infected intragastrically with Candida albicans by inoculating the mammary glands of the lactating mothers with viable blastospores and allowing the infants to suckle . Levels of colonization were determined by quantitative cultures of stomachs and selected organs at various intervals up to 6 weeks after infection . The results demonstrate that a high percentage of infant mice can be colonized in this manner and that the colonization is of long duration . Although systemic spread of the yeast to other visceral organs did occur, the numbers of yeasts recovered were minimal.

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