Transfusion, 1995 Jul, 35(7), 605 - 11 Protection of human polymorphonuclear leukocyte function from the deleterious effects of isolation, irradiation, and storage by interferon-gamma and granulocyte-colony-stimulating factor; Rex JH et al.; BACKGROUND: Fungal infections represent a difficult challenge to clinicians caring for neutropenic patients with hematologic malignancies, as antifungal therapy often has limited success in that setting . One promising yet problematic alternative approach is leukocyte transfusion . The isolation of polymorphonuclear leukocytes (PMNs) induces apoptosis and functional deterioration, and irradiation to prevent transfusion-associated graft-versus-host disease causes further functional deterioration . STUDY DESIGN AND METHODS: The ability of interferon-gamma and granulocyte-colony-stimulating factor (G-CSF), used both alone and in combination, to protect PMNs after 0 or 20 hours' storage in cell culture (as a model for function after transfusion) and irradiation with 0, 5, or 30 Gy was studied . RESULTS: Without cytokine treatment, 20-hour-old PMNs showed marked apoptosis, no appreciable chemotaxis, and no ability to kill Candida albicans . In contrast, cytokine treatment significantly reduced apoptosis and protected chemotaxis, C . albicans killing, and surface-receptor expression from both storage and irradiation . Although the majority of the benefit appeared to be due to G-CSF, consistent trends suggested better function of PMNs after combined treatment with interferon-gamma and G-CSF . CONCLUSION: Judicious use of cytokines may preserve PMN function . These findings have important implications for the transfusion of PMNs to cytopenic patients. J Bacteriol, 1995 Jul, 177(13), 3788 - 92 Covalent association of beta-1,3-glucan with beta-1,6-glucosylated mannoproteins in cell walls of Candida albicans; Kapteyn JC et al.; Yeast and hyphal walls of Candida albicans were extracted with sodium dodecyl sulfate (SDS) . Some of the extracted proteins reacted with a specific beta-1,6-glucan antiserum but not with a beta-1,3-glucan antiserum . They lost their beta-1,6-glucan epitope after treatment with ice-cold aqueous hydrofluoric acid, suggesting that beta-1,6-glucan was linked to the protein through a phosphodiester bridge . When yeast and hyphal walls extracted with SDS were subsequently extracted with a pure beta-1,3-glucanase, several mannoproteins that were recognized by both the beta-1,6-glucan antiserum and the beta-1,3-glucan antiserum were released . Both epitopes were sensitive to aqueous hydrofluoric acid treatment, suggesting that beta-1,3-glucan and beta-1,6-glucan are linked to proteins by phosphodiester linkages . The possible role of beta-glucans in the retention of cell wall proteins is discussed. J Infect Dis, 1995 Jul, 172(1), 192 - 8 Nitric oxide enhances resistance of SCID mice to mucosal candidiasis; Vazquez-Torres A et al.; The capacity of macrophages from SCID and C.B-17 mice to kill Candida albicans via a nitric oxide (NO)-dependent pathway and the contribution of NO in resistance to mucosal candidiasis were assessed . In vitro, an inhibitor of NO synthase (NOS) reduced the candidacidal activity and nitrite-producing capacity of activated resident peritoneal macrophages from immunocompetent C.B-17 and immunodeficient SCID mice . In vivo, stomachs from gnotobiotic SCID mice that were colonized with a pure culture of C . albicans had low-grade infections and expressed inducible NOS (iNOS) mRNA . C . albicans-monoassociated SCID mice treated with an inhibitor of NOS had more severe orogastric candidiasis than controls . These data suggest that NO contributes to the candidacidal capacity of activated macrophages from C.B-17 and SCID mice and that NO synthesized by iNOS may contribute to the resistance of SCID mice to mucosal candidiasis. Turk J Pediatr, 1995 Jul-Sep, 37(3), 247 - 52 Amphotericin B in the treatment of candida meningitis in three neonates; Aydin M et al.; Candidiasis is an opportunistic infection and may result in significant morbidity and mortality in neonates . Cerebral candidiasis is rare and usually associated with systemic candidiasis . Information concerning the toxicity and efficacy of antifungal therapy for neonates is limited . In this report, we present three neonates with candidiasis . All of the patients were premature with low birth weights, and received antibiotic therapy for one to four weeks before the onset of candidiasis . Candida albicans was isolated from cerebrospinal fluid cultures . Amphotericin B was given administered at an initial dose of 0.25 mg/kg/day intravenously (IV) and increased to a dosage of 2 mg/kg/day, and therapy was continued for three to four weeks . A transient and mild elevation in hepatic enzyme concentration was observed in two patients, and transient thrombocytopenia occurred in all of them. Antimicrob Agents Chemother, 1995 Jul, 39(7), 1538 - 41 Inhibition of sterol 4-demethylation in Candida albicans by 6-amino-2-n-pentylthiobenzothiazole, a novel mechanism of action for an antifungal agent; Kuchta T et al.; The effects of 6-amino-2-n-pentylthiobenzothiazole (APB), a new antifungal agent, on ergosterol biosynthesis in Candida albicans and Saccharomyces cerevisiae were studied, using {14C}acetate incorporation . In C . albicans, the inhibition of growth was accompanied by a marked inhibition of acetate incorporation in 4-desmethylsterols, with a significant portion of the radiolabel being incorporated in 4,4-dimethylsterols, lanosterol, and 4,4-dimethylzymosterol and minor amounts being incorporated in 4-methylsterols and squalene . The data are interpreted as evidence of a block of the ergosterol biosynthesis pathway at the level of 4-demethylation of 4,4-dimethylzymosterol, with partial inhibition of lanosterol 14-dimethylation and squalene epoxidation also being possible . In 6-amino-2-n-pentylthiobenzothiazole-treated S . cerevisiae, a significant amount of the radiolabel was incorporated also in 4-methylsterols, 4-methylzymosterol, and 4-methylfecosterol, indicating that in this microorganism there are different sensitivities of the two 4-demethylations and that the pathway is blocked at the level of 4-demethylation of 4-methylsterols. Antimicrob Agents Chemother, 1995 Jul, 39(7), 1512 - 6 Patterns of in vitro activity of itraconazole and imidazole antifungal agents against Candida albicans with decreased susceptibility to fluconazole from Spain; Martinez-Suarez JV et al.; Two groups of recent clinical isolates of Candida albicans consisting of 101 isolates for which fluconazole MICs were < or = 0.5 microgram/ml (n = 50) and > or = 4.0 micrograms/ml (n = 51), respectively, were compared for their susceptibilities to fluconazole, clotrimazole, miconazole, ketoconazole, and itraconazole . Susceptibility tests were performed by a photometer-read broth microdilution method with an improved RPMI 1640 medium supplemented with 18 g of glucose per liter (RPMI-2% glucose; J . L . Rodriguez-Tudela and J . V . Martinez-Suarez, Antimicrob . Agents Chemother . 38:45-48, 1994) . Preparation of drugs, basal medium, and inocula was done by the recommendations of the National Committee for Clinical Laboratory Standards . The MIC endpoint was calculated objectively from the turbidimetric data read at 24 h as the lowest drug concentration at which growth was just equal to or less than 20% of that in the positive control well (MIC 80%) . In vitro susceptibility testing separated azole-susceptible strains from the strains with decreased susceptibilities to azoles if wide ranges of concentrations (20 doubling dilutions) were used for ketoconazole, miconazole, and clotrimazole . By comparison with isolates for which fluconazole MICs were < or = 0.5 microgram/ml, those isolates for which fluconazole MICs were > or = 4.0 micrograms/ml were in general less susceptible to other azole drugs, but different patterns of decreased susceptibility were found, including uniform increases in the MICs of all azole derivatives, higher MICs of several azoles but not others, and elevated MICs of fluconazole only . On the other hand, decreased susceptibility to any other azole drug was never found among strains for which MICs of fluconazole were lower. Sex Transm Dis, 1995 Jul-Aug, 22(4), 221 - 7 Screening for Chlamydia trachomatis infection in pregnant women in Martinique; Chout RT et al.; GOAL OF THIS STUDY: To determine the prevalence of Chlamydia trachomatis urogenital infection and to identify behavioral, demographic, and clinical factors associated with the infection in pregnant women in Martinique . STUDY DESIGN: One-thousand-four-hundred-eleven patients 15-39 years old, at 10-16 weeks of gestation and attending the prenatal clinic at Lamentin Hospital, were tested for Chlamydia trachomatis infection of the cervix and urethra using tissue culture . RESULTS: Chlamydia trachomatis was isolated from 375 (26.7%) women; 34% of them were positive in the cervix and urethra, 58% in the cervix only, and 8% in the urethra only . Factors found by multivariate analysis to be significantly associated with chlamydial infection were age less than 25 years, first intercourse at less than 18 years old, previous induced abortions, mucopurulent cervicitis, and repeated candidiasis . CONCLUSIONS: None of the factors associated with chlamydial infection was sensitive enough to permit efficient selective screening . It is cost effective to recommend a routine screening for chlamydial infection together with an educational programPIP: To determine the prevalence of Chlamydia trachomatis urogenital infection among pregnant women in Martinique, 1411 consecutive women presenting to Lamentin Hospital for their initial prenatal visit between 1988-90 underwent specimen collection and extensive interviews . The mean age of study subjects was 27.1 years and the mean number of life-time sex partners was 3.2 . C . trachomatis was isolated from 375 women (26.7%), two-thirds of whom were asymptomatic . There was an inverse correlation between age and infection rate; 164 (43.7%) infected women were under 25 years of age . 34% had evidence of infection in both the cervix and urethra, 58% in the cervix only, and 8% in the urethra only . Other sexually transmitted pathogens with a high prevalence in this group included Ureaplasma urealyticum (39.9%), Candida albicans (32%), and Trichomonas vaginalis (13.7%) . Factors that correlated significantly with chlamydia infection by multivariate analysis were age less than 25 years, first intercourse less than 18 years, previous induced abortion, cervicitis, and repeated candidiasis . However, no single risk factor or constellation of risk factors was sufficiently sensitive to form the basis of a selective screening program . Considering the serious maternal and infant complications of C . trachomatis infection, routine screening in pregnant women is urged . Given a prevalence rate of 27%, 1630 infected pregnant women should be identified each year in Martinique . The cost of screening and treating these women and their partners would be US$250,000 compared to $1.2 million required to treat chlamydia-related conjunctivitis and pneumonia in infants and postpartum salpingitis in mothers . Rev Fr Gynecol Obstet, 1995 Jul-Sep, 90(7-9), 345 - 51 {A comparative study of 2 ways of clinical management in premature rupture of the membranes at term: temporization versus labor induction}; Kouam L et al.; Two defined management approaches, temporization limited to 48 hours and immediate induction of labor, for premature rupture of the membranes at term were compared in a prospective study between January 1 1991 and November 30 1993 in the Maternity Unit of Yaounde University Hospital . During this period, 268 cases of premature rupture of the membranes were seen among 3252 deliveries, i.e . an incidence of 8.2% . In the temporization group (153 cases), spontaneous onset of labor was effective in 95 patients (62.1%) within 12 hours and in 137 patients (89.5%) within 24 hours after premature rupture of the membranes . Spontaneous deliveries in this temporization group accounted for 129 cases (92.8%) . In the induction of labor group, spontaneous delivery occurred in 119 cases (93.2%) . There were ten cesareans in the temporization group and eight cesareans and two vacuum cup extractions in the induction group . Short term (24 hours) prophylactic antibiotics were given to 34 patients, i.e . 16 cases in which the duration of rupture of the membranes was more than 24 hours and 18 cases of cesarean section . Maternal infections concerned 18 cases (6.7%) including 12 cases (4.4%) of malaria . Microbiology of vaginal swabs revealed 6 cases of pseudomonas, 4 cases of staphylococcus aureus and 3 of candida albicans . Neonatal infections confirmed by blood culture and assay of C-reactive-protein involved 24 cases (20.3%) . There were three fetal deaths, i.e . perinatal mortality of 1.1% . Risk factors, in these three fetal deaths, included postmaturity (1 case).(ABSTRACT TRUNCATED AT 250 WORDS) Biochemistry, 1995 Jun 20, 34(24), 7896 - 903 Mechanism of irreversible inactivation of phosphomannose isomerases by silver ions and flamazine; Wells TN et al.; Silver ions and silver-containing compounds have been used as topical antimicrobial agents in a variety of clinical situations . We have previously shown that the enzyme phosphomannose isomerase (PMI) is essential for the biosynthesis of Candida albicans cell walls . In this study, we find that PMI can be inhibited by silver ions . This process is shown to be irreversible, and is a two-step process, involving an intermediate complex with a dissociation constant, Ki, of 59 +/- 8 microM, and a maximum rate of inactivation of 0.25 +/- 0.04 min-1 in 50 mM Hepes buffer, pH 8.0 at 37 degrees C . The enzyme can be protected against this inactivation by the substrate mannose 6-phosphate, with a dissociation constant of 0.31 +/- 0.04 mM, close to its Km value . Flamazine (silver sulfadiazine) is a silver-containing antibiotic which is used clinically as a topical antimicrobial and antifungal agent . We compared the ability of silver sulfadiazine and two other silver-containing compounds to irreversibly inactivate C . albicans PMI . The addition of the organic moiety increased the affinity of the compounds, with silver sulfadiazine showing a Ki of 190 +/- 30 nM . In all cases, the maximum inhibition rate was similar, implying a similar rate-determining step . Silver sulfadiazine does not inhibit Escherichia coli PMI, and this suggests a role of the only free cysteine, Cys-150, in the inactivation process . To confirm this, we mutated this residue to alanine in C . albicans PMI . The resultant Cys150 --> Ala mutant protein showed similar Vm and Km values to the wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) FEMS Microbiol Lett, 1995 Jun 15, 129(2-3), 103 - 13 Adherence of Candida albicans to host cells; Pendrak ML et al.; Research devoted to uncovering the mechanisms of adherence of Candida albicans to human tissue is reviewed . The physical aspects of adherence of the fungus to host cells and the biochemical and molecular features, as far as they are known, are discussed . Relevant pre- and post-adherence events in the pathogenesis of disease caused by this fungus are also noted . Putative adhesins and surface receptors of C . albicans for host proteins are discussed in detail. J Leukoc Biol, 1995 Jun, 57(6), 842 - 50 Relationship of phospholipase C- and phospholipase D-mediated phospholipid remodeling pathways to respiratory burst activation in human neutrophils stimulated by Candida albicans hyphae; Meshulam T et al.; Neutrophil (PMN) oxidant release, a key component of defenses against disseminated candidiasis, was preceded by oxidant generation after stimulation by Candida albicans hyphae . Opsonized or unopsonized hyphae triggered phospholipase D (PLD) activation within 5 or 30 s, respectively, forming 1-O-alkyl-phosphatidic acid (alkyl-PA) or 1-O-alkyl-phosphatidyl-ethanol in the presence of ethanol . Ethanol, which competitively lowers phosphatidic acid (PA) production, caused dose-dependent inhibition of superoxide (O2-) generation after hyphal stimulation but altered neither baseline-unstimulated O2- production nor responses to phorbol myristate acetate . PA rises evoked by unopsonized hyphae began 2 min before significant O2- release, also preceding both phospholipase C activation and cytosolic Ca2+ rises . Diacylglycerol (DAG) rose in two distinct phases after stimulation by opsonized or unopsonized hyphae, peaking briefly after 60 or 120 s, respectively, followed by prolonged secondary rises . Initial DAG rises preceded inositol triphosphate elevations evoked by unopsonized hyphae . Though PA rose before DAG, no dephosphorylation of PA to form 1-O-alkyl-DAG was noted . Propranalol, which increases PA accumulation by inhibiting PA phosphohydrolase, lowered PMN O2- responses to hyphae . Early DAG rises temporally overlapped respiratory burst initiation but PMN responses to hyphae were unchanged by a DAG kinase inhibitor, R59022, which blocks phosphorylation of DAG to PA and enhances DAG accumulation . Thus, neither PA nor DAG accumulation individually accounted for triggering PMN O2- responses to hyphae . PLD activation and PA production may facilitate PMN fungicidal responses to hyphae but play an indirect role in initiating the respiratory burst. J Clin Endocrinol Metab, 1995 Jun, 80(6), 1948 - 55 Priming of human polymorphonuclear neutrophilic leukocytes by insulin-like growth factor I: increased phagocytic capacity, complement receptor expression, degranulation, and oxidative burst; Bjerknes R et al.; Insulin-like growth factor I (IGF-I) is a GH-dependent peptide regulating mammalian growth that seems to be of importance for the normal development and function of the immune system . Polymorphonuclear neutrophilic leukocytes (PMNLs) are terminally differentiated phagocytes essential for host defense, and in the present study, recombinant human IGF-I was shown to be a powerful primer of mature human PMNLs . IGF-I augmented the PMNL phagocytosis of both immunoglobulin G-opsonized Staphylococcus aureus and complement-opsonized Candida albicans . In addition, the growth factor increased PMNL complement receptor expression {complement receptors 1 (CD35) and 3 (CD11b)} and primed the cells to stronger f-met-leu-phe-induced degranulation of both specific and azurophilic granules {markers: CD11b, CD35 and CD67 (specific granules); CD63 (azurophilic granules)} . In contrast, IGF-I did not alter the PMNL surface expression of Fc gamma RI (CD64), Fc gamma RII (CDw32), or Fc gamma RIII (CD16) . PMNLs exposed to IGF-I increased their f-met-leu-phe and phorbol myristate acetate-induced oxidative burst, as evaluated by hydrogen peroxide production, whereas IGF-I did not influence PMNL actin polymerization . The priming of PMNLs by IGF-I was dependent on time and concentration, and saturating amounts of a monoclonal antibody to the IGF-I receptor blocked the priming of PMNLs by this peptide . These experiments demonstrate that IGF-I can selectively stimulate mature PMNL functions, providing further evidence for the interaction between the immune and the endocrine systems. Clin Exp Immunol, 1995 Jun, 100(3), 419 - 24 HIV-specific lymphoproliferative responses in asymptomatic HIV-infected individuals; Pontesilli O et al.; In vitro lymphoproliferative responses to HIV-1 recombinant antigens (gp160, p24, and Rev protein) were studied in 83 patients with asymptomatic HIV-1 infection (CDC groups II and III) and circulating CD4 lymphocyte numbers > 400/mm3 . Significant response to at least one of the three antigens was detected in 52.4% of the subjects, but the responses were weak, and concordance of the response to the three antigens was rare, the frequency of individuals responding to each antigen not exceeding 22.4% . Increasing frequencies of response were observed when recall antigens (tetanus toxoid and Candida albicans glycomannoprotein) (65.5%) and anti-CD3 MoAb (76.6%) were used as stimuli . Although a significant association between lymphocyte response to p24, but not gp160, and steadiness of CD4 lymphocyte numbers before the assay was observed, no predictive value for lack of CD4 cell decrease was confirmed for either antigen, and fluctuation of the responses to HIV antigens was seen during subsequent follow up . The panel of T cell assays used could be regarded as appropriate for monitoring both HIV-specific responses and T lymphocyte function during immunotherapy with soluble HIV antigens. Obstet Gynecol, 1995 Jun, 85(6), 993 - 8 Torulopsis glabrata vaginitis; Spinillo A et al.; OBJECTIVE: To study the sociodemographic risk factors and clinical features of Torulopsis glabrata vaginal infection . METHODS: We evaluated the sociodemographic and clinical characteristics of 86 consecutive symptomatic women attending a vaginitis clinic and isolated T glabrata . Case patients were compared with a control group of 174 asymptomatic women with negative vaginal cultures and an additional group of 625 symptomatic women with vaginal cultures positive for Candida albicans . In addition, the sensitivity of the isolates to the more common antimycotic agents used was tested by the modified Kirby-Bauer method . RESULTS: Patients with T glabrata vaginal infection were from lower socioeconomic backgrounds and had less education . They were more likely to use vaginal tampons and to be seropositive for human immunodeficiency virus than were negative controls . Compared with C albicans infection, T glabrata was more frequent among women over 38 years of age and in those with less education and of lower social class . In logistic regression analysis, T glabrata was associated more frequently with recurrent vaginal candidiasis than was C albicans (odds ratio 2.46, 95% confidence interval 1.33-4.54; P = .004) . Six of the 86 (7%) T glabrata isolates and none of the C albicans isolates (P < .001 by Fisher exact test) were resistant to the imidazole derivatives tested . CONCLUSION: Torulopsis glabrata was isolated in 10% of women with vulvovaginal candidiasis attending a vaginitis clinic . This infection was associated with recurrent vaginitis in almost one-third of case patients presenting with symptoms. J Infect Dis, 1995 Jun, 171(6), 1664 - 7 Defective killing of Candida albicans hyphae by neutrophils from beige mice; Jones-Carson J et al.; The candidacidal activity of neutrophils from BALB/c, C.B-17 +/+, C.B-17 scid/scid, scid/scid-bg/bg, C57BL/6 bg/+, C57BL/6 bg/bg, NIH III bg/bg-nu/+, and bg/bg-nu/nu mice was assessed . Killing of blastoconidia was moderately deficient with neutrophils from 2 strains of homozygous beige mice; however, neutrophils from all homozygous beige strains had a significantly decreased capacity to kill Candida albicans hyphae . This is the first demonstration of a decreased capacity of beige mouse neutrophils to kill C . albicans hyphae . The latter defect could be related to the enhanced susceptibility of beige mice to candidiasis. J Infect Dis, 1995 Jun, 171(6), 1545 - 52 Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation--a prospective, randomized, double-blind study; Slavin MA et al.; A randomized, double-blind, placebo-controlled trial assessed the efficacy and toxicity of 400 mg/day fluconazole in preventing fungal infections during the first 75 days after marrow transplantation . During prophylaxis, systemic fungal infections occurred in 10 (7%) of 152 fluconazole-treated patients compared with 26 (18%) of 148 placebo-treated patients (P = .004) . There were no Candida albicans infections in fluconazole recipients compared with 18 in placebo recipients (P < .001) and no significant increase in Candida infections other than C . albicans . Fluconazole also significantly reduced the incidence of superficial fungal infections (P < .001), fungal colonization (P = .037), and empiric amphotericin B use (P = .005) . The probability of survival was improved in fluconazole recipients, in whom 31 deaths occurred up to day 110 after transplantation compared with 52 deaths in placebo recipients (P = .004) . No clinically significant toxicity was detected with fluconazole use . Prophylactic fluconazole was safe and significantly reduced systemic fungal infections with other benefits, including improved survival at day 110 after marrow transplantation. J Infect Dis, 1995 Jun, 171(6), 1539 - 44 Mortality of Candida albicans-infected mice is facilitated by superinfection of Escherichia coli or administration of its lipopolysaccharide; Akagawa G et al.; Pathogenesis of complex infection with Candida albicans and gram-negative bacteria was studied by determining the influence of infection with Escherichia coli or injection of E . coli lipopolysaccharide (LPS) on mortality of C . albicans-infected mice . Mice were infected intravenously with lethal doses of C . albicans, then treated intravenously at various times with viable E . coli or E . coli LPS, which individually were not lethal . Treatments 3 h after C . albicans infection clearly facilitated the death of the mice . Corresponding to this facilitated death, production of tumor necrosis factor (TNF) in sera was augmented 2 h after LPS injection into the infected mice . Similar increased production of TNF was also observed in mice treated with a nonlethal combination of heat-killed C . albicans and LPS . The number of viable C . albicans in kidneys of the infected mice was increased by LPS treatment, which was assumed to be the main cause of the greater mortality rate. J Bacteriol, 1995 Jun, 177(11), 2971 - 6 D-arabitol metabolism in Candida albicans: construction and analysis of mutants lacking D-arabitol dehydrogenase; Wong B et al.; Candida albicans produces large amounts of the acyclic pentitol D-arabitol in culture and in infected animals and humans, and most strains also grow on minimal D-arabitol medium . An earlier study showed that the major metabolic precursor of D-arabitol in C . albicans was D-ribulose-5-PO4 from the pentose pathway, that C . albicans contained an NAD-dependent D-arabitol dehydrogenase (ArDH), and that the ArDH structural gene (ARD) encoded a 31-kDa short-chain dehydrogenase that catalyzed the reaction D-arabitol + NAD <=> D-ribulose + NADH . In the present study, we disrupted both ARD chromosomal alleles in C . albicans and analyzed the resulting mutants . The ard null mutation was verified by Southern hybridization, and the null mutant's inability to produce ArDH was verified by Western immunoblotting . The ard null mutant grew well on minimal glucose medium, but it was unable to grow on minimal D-arabitol or D-arabinose medium . Thus, ArDH catalyzes the first step in D-arabitol utilization and a necessary intermediate step in D-arabinose utilization . Unexpectedly, the ard null mutant synthesized D-arabitol from glucose . Moreover, 13C nuclear magnetic resonance studies showed that the ard null mutant and its wild-type parent synthesized D-arabitol via the same pathway . These results imply that C . albicans synthesizes and utilizes D-arabitol via separate metabolic pathways, which was not previously suspected for fungi. Infect Immun, 1995 Jun, 63(6), 2378 - 81 Beta-1,2-linked oligomannosides from Candida albicans act as signals for tumor necrosis factor alpha production; Jouault T et al.; Different cell wall components from Candida albicans have been shown to stimulate murine macrophages for tumor necrosis factor alpha (TNF-alpha) secretion . All of these molecules contain beta-1,2-oligomannosides . In order to examine their role in TNF-alpha production, acid-labile oligosaccharides, released from C . albicans VW32 cell wall phosphopeptidomannan by mild acid hydrolysis, and previously shown to correspond to homopolymers of beta-1,2-linked mannopyranosyl units, were separated by gel filtration chromatography according to their degree of polymerization . Murine macrophages incubated with purified oligomannosides (M2 to M8) released TNF-alpha to an extent which was dependent on, although not directly correlated with, the length of the mannosyl chain . Slight activity was observed with M4 and M5; M6 and M7 had virtually no effect, whereas M8 was associated with strong TNF-alpha release . This effect of M8 was dose dependent and was not altered by polymyxin B, known to interfere with lipopolysaccharide-induced TNF-alpha production . These results suggest that stimulation of TNF-alpha release by C . albicans glycoconjugates containing beta-1,2-linked oligomannosides may be due, at least in part, to the presence of these components. Infect Immun, 1995 Jun, 63(6), 2173 - 9 Evidence for the presence of collagenous domains in Candida albicans cell surface proteins; Sepulveda P et al.; Rabbit polyclonal antibodies (PAbs) directed towards the amino-terminal cysteine-rich 7S domain (PAb anti-7S), the major internal collagenous domain (PAb anti-type IV), and the C-terminal noncollagenous region (PAb anti-NC1) of the type IV collagen molecule were probed by indirect immunofluorescence against Candida albicans blastoconidia and germinated blastoconidia . Most nongerminating cells and mother blastoconidia from which germ tubes originated showed strong fluorescence when PAb anti-7S was used, whereas with PAb anti-type IV, fluorescence was found almost exclusively on the surface of filamentous forms . A patched fluorescent pattern rather than a homogenous confluent fluorescence was observed in all cases . No fluorescent cells were observed with PAb anti-NC1 . By Western immunoblotting, PAb anti-type IV cross-reacted primarily with a polypeptide of 37 kDa present in wall extracts obtained from intact cells of both growth forms by treatment with beta-mercaptoethanol, whereas PAb anti-7S recognized a major 58-kDa antigen also present in both extracts, along with some other high-molecular-mass (> 106-kDa) polydisperse species present only in the material released from blastoconidia with beta-mercaptoethanol . No reactive bands were observed when PAb anti-NC1 was used as a probe in Western immunoblotting experiments . The sensitivities or resistances to collagenase digestion of the different polypeptides that cross-reacted with PAbs anti-type IV and anti-7S suggest the existence of cell wall components in C . albicans that contain epitopes that mimic the collagenous domains of the type IV collagen molecule. Infect Immun, 1995 Jun, 63(6), 2126 - 32 Comparative study of the C3d receptor and 58-kilodalton fibrinogen-binding mannoproteins of Candida albicans; Lopez-Ribot JL et al.; Using polyclonal antibodies (PAbs) raised against the Candida albicans C3d receptor (CR2; PAb anti-CR2) and the 58-kDa fibrinogen-binding mannoprotein (mp58; PAb anti-mp58) as well as ligand interactions, we have studied the relationship between these two receptors . In an indirect immunofluorescence assay with germ tubes, greater intensity was observed on the mother blastoconidium when PAb anti-CR2 was used, whereas greater intensity was localized to the hyphal extension when PAb anti-mp58 or binding of soluble fibrinogen was used . No competition or change in the fluorescence pattern was observed in dual-labeling experiments with PAb anti-CR2 and either fibrinogen or PAb anti-mp58 . Binding competition also was not observed in an enzyme-linked immunosorbent assay using the components present in a beta-mercaptoethanol extract from the cell wall of germ tubes . In immunoblots, PAb anti-CR2 recognized three different discrete bands with apparent molecular masses of 21, 40, and 66 kDa in the beta-mercaptoethanol extracts from the cell wall, whereas a different, single, broader band with an apparent molecular mass of 58 kDa was detected with PAb anti-mp58 . However, when nondenaturing conditions were used to separate the materials present in the cell wall extracts, no reactivity could be detected on Western blots (immunoblots) with PAb anti-mp58 . When PAb anti-CR2 was used for analysis, a single band migrating in the area corresponding to approximately 40 kDa was detected . These observations suggest a higher molecular weight for mp58 and one or more of the components detected with PAb anti-CR2 in their native state. Arch Oral Biol, 1995 Jun, 40(6), 581 - 4 Modulation of the anti-Candida activity of apo-lactoferrin by dietary sucrose and tunicamycin in vitro; Nikawa H et al.; The sensitivity to apo-lactoferrin (apo-LF) of two oral isolates each of Candida albicans and C . krusei preincubated in either sucrose- or tunicamycin-supplemented media was investigated . Known apo-LF-sensitive isolates of both C . albicans and C . krusei demonstrated significantly increased resistance to apo-LF when preincubated in sucrose-supplemented media, but such preincubation had no effect on an apo-LF-resistant isolate of C . albicans, irrespective of the sugar concentration in the medium . Surprisingly, an apo-LF-resistant isolate of C . krusei demonstrated increased susceptibility to apo-LF when preincubated in sucrose . Further, when preincubated with tunicamycin, a chemical that interferes with candidal cell-wall formation, the susceptibility to apo-LF of the resistant isolates increased significantly . These results, when extrapolated in vivo, imply that dietary sucrose may diminish the anticandidal potency of salivary lactoferrin . However, the aberrant behaviour of a single isolate of C . krusei under these circumstances is possibly due to the different cell-wall structure of this yeast and needs to be further investigated. Arch Oral Biol, 1995 Jun, 40(6), 577 - 9 Oral Candida albicans biotypes in Chinese patients with and without oral candidosis; Xu YY et al.; A total of 53 oral Candida albicans isolates from Chinese patients with clinically diagnosed oral candidosis (27 patients) or without overt signs and mycological manifestations of infection (26) were biotyped using two commercially available API micromethod kits and a boric acid-resistance test . There were no significant differences in the biotypes in health and disease, although the biotype A1R was present only in diseased individuals . The biotype A1S accounted for 21% of the total isolates, as in a number of other previous studies from the West . However, 14 of the 27 biotypes characterized were new biotypes that have not been described before . These preliminary data indicate that biotypic profile of C . albicans may bear no relation to the virulence of the isolates, and that diverse subtypes of the fungus are globally prevalent. Microbiology, 1995 Jun, 141 ( Pt 6), 1301 - 8 Neocallimastix frontalis enolase gene, enol: first report of an intron in an anaerobic fungus; Durand R et al.; A DNA clone containing a putative enolase gene was isolated from a genomic DNA library of the anaerobic fungus Neocallimastix frontalis . It was deduced from sequence comparisons that the enolase gene was interrupted by a large 331 bp intron . The enolase gene, termed enol, has an ORF of 1308 bp and encodes a predicted 436 amino acid protein . The deduced amino acid sequence shows high identity (71.5-71%) to those of enolases from the yeasts Saccharomyces cerevisiae and Candida albicans . The G+C content of the enolase coding sequence (43.8 mol%) is considerably higher than the G+C content of the intervening sequence (14.2 mol%) or the 5' and 3' non-translated flanking sequences (15.2 and 4.7 mol%, respectively) . The codon usage of the N . frontalis enolase gene was very biased as has been found for the highly expressed genes of yeast and filamentous fungi . The gene has all the canonical features (polyadenylation signal, intron splicing boundaries) of genes isolated from aerobic filamentous fungi . Only one enolase gene could be detected in N . frontalis genomic DNA by Southern analysis with a homologous probe . RNA analysis detected a single enolase transcript of about 1.6 kb . When mycelium was grown on glucose, levels of enolase mRNA were markedly increased by comparison with enolase mRNA levels in mycelium grown on cellulose, suggesting that expression of the N . frontalis enolase gene was transcriptionally regulated by the carbon source. Cytometry, 1995 Jun 1, 20(2), 127 - 33 Rapid flow cytometric method for measuring lymphocyte subset activation; Maino VC et al.; Standard in vitro methods for assessing T-cell activation have typically measured either the proliferative responses of peripheral blood mononuclear cell (PBMC) cultures to various provocative stimuli employing tritiated thymidine incorporation or the secretion of specific cytokines from activated cells . These bulk assay methods suffer the drawback of being lengthy assays, and, in addition, they do not provide information about functional responses of individual lymphocyte subsets . This report describes a three-color flow cytometric method for the rapid analysis (4 hours) of individual T-cell subsets in whole blood responding to various provocative stimuli, including pokeweed mitogen, the comitogenic monoclonal antibodies (mAbs) CD2/CD2R, the superantigen staphylococcal enterotoxin B (SEB), and the specific antigen Candida albicans . After 4 hours, CD69 expression in response to CD2/CD2R paralleled thymidine incorporation measured after 72 hours . Variations in the proportions of CD4+ and CD4- T cells expressing CD69 were observed with different stimuli . These observations demonstrate the potential of multiparameter flow cytometry for the investigation of functional responses of individual T-cell subsets to a variety of stimuli in whole blood. J Clin Microbiol, 1995 Jun, 33(6), 1501 - 9 Colonizing populations of Candida albicans are clonal in origin but undergo microevolution through C1 fragment reorganization as demonstrated by DNA fingerprinting and C1 sequencing; Lockhart SR et al.; The genetic homogeneity of nine commensal and infecting populations of Candida albicans has been assessed by fingerprinting multiple isolates from each population by Southern blot hybridization first with the Ca3 probe and then with the 0.98-kb C1 fragment of the Ca3 probe . The isolates from each population were highly related, demonstrating the clonal origin of each population, but each population contained minor variants, demonstrating microevolution . Variation in each case was limited to bands of the Ca3 fingerprint pattern which hybridized with the 0.98-kb C1 fragment . The C1 fragment was therefore sequenced and demonstrated to contain an RPS repetitive element . The C1 fragment also contained part or all of a true end of the RPS element . These results, therefore, demonstrate that most colonizing C . albicans populations in nonimmuno-suppressed patients are clonal, that microevolution can be detected in every colonizing population by C1 hybridization, and that C1 contains the repeat RPS element. Clin Exp Allergy, 1995 Jun, 25(6), 522 - 8 Detection of IgE antibody against Candida albicans enolase and its crossreactivity to Saccharomyces cerevisiae enolase; Ito K et al.; Candida albicans 46 kDa protein, a glycolytic enolase enzyme, is an important allergen of the yeast . The purpose of the study was to detect circulating IgE and IgG antibodies against C . albicans enolase (CAE) . We isolated CAE using sequential DEAE Sephacel and P11 column chromatography from spheroplasts of C . albicans, and detected IgE and IgG antibody against CAE by immunoblotting . Crossreactivity of enolase of C . albicans and Saccharomyces cerevisiae was also examined by immunoblotting and immunoblot inhibition test . Among 54 sera with positive IgE RAST to C . albicans, IgE antibody against CAE was detected in 20 sera (37%) and IgG antibody in 27 sera (50%) . The allergenic potency of CAE was confirmed using a skin-prick test in three patients . Simultaneous IgE binding to S . cerevisiae enolase was only observed in four out of 20 sera reacting to CAE . Pre-treatment of sera with CAE completely inhibited IgE binding to S . cerevisiae enolase . Whereas the latter only partially inhibited IgE binding to CAE . These results suggest that CAE shares some crossreacting epitopes with S . cerevisiae enolase, representing minor components of CAE but dominant segments of S . cerevisiae enolase. Trends Microbiol, 1995 Jun, 3(6), 237 - 40 A TH1-TH2-like switch in candidiasis: new perspectives for therapy; Puccetti P et al.; An imbalance in TH1-type and TH2-type responses may allow Candida albicans to modify the host response to favor its own persistence . This hypothesis has important consequences for allergy, autoimmunity and co-infection, and also highlights a potential role for cytokine and anti-cytokine therapy in Candida-related pathology. Eur J Immunol, 1995 Jun, 25(6), 1559 - 65 Interleukin-4 and -10 exacerbate candidiasis in mice; Tonnetti L et al.; Neutralization of endogenous interleukin (IL)-4 or IL-10 in mice with Candida albicans infection initiates or accelerates development of a T helper (Th)1-associated protective response . Here, we report the effect of IL-4 and IL-10 administration on the course of systemic or gastrointestinal (GI) candidiasis and on the development of Th immunity using yeast/host combinations that result either in Th1-associated self-limiting infection (healer mice) or in Th2-associated progressive disease (nonhealer mice) . Treatment with IL-4 or IL-10 greatly exacerbated the course of systemic infection in nonhealer mice and rendered healer mice, inoculated with attenuated yeast cells, susceptible to infection . Under the latter conditions of yeast challenge and IL-4/IL-10 administration, the development of a fatal disease was associated with inhibition of IL-12 production and detection of progressive Th2 cell dominance . In contrast, in healer mice allowed to resolve their infections and to develop long-lived anti-candidal resistance, the expression of this acquired resistance was not impaired by IL-4 and/or IL-10, as shown by the outcome of reinfection with virulent yeast cells . In the GI model of infection, both IL-4 and IL-10 were found to exacerbate the course of infection and to induce the appearance of CD4+ T cells producing high levels of IL-4 and IL-10 in Peyer's patches . These findings demonstrate that exogenous IL-4 and IL-10 may greatly affect the development of Th responses to C . albicans in vivo, but do not modify the expression of established and predominant Th1 cell reactivity. Exp Mycol, 1995 Jun, 19(2), 101 - 10 Detection of myosin immunoanalogue in the yeast Candida albicans; Ghazali M et al.; Detection and localization of myosin immunoanalogue protein in the yeast Candida albicans were achieved by immunoblotting, indirect immunofluorescence assay, and immunoelectron microscopy . A polypeptide with an M(r) about 110,000, from cytosolic extract and insoluble fraction in the corresponding membrane pellet, was reacted with polyclonal and monoclonal antibodies raised against vertebrate muscle myosin . This protein was located by immunofluorescence and immunoelectron microscopy in the cell cortex along the plasmalemma, in the cytoplasm, and in the septum corresponding to bud scar region situated between the yeast-mother cell and the bud. Nat Med, 1995 Jun, 1(6), 552 - 7 Gamma delta T cell-induced nitric oxide production enhances resistance to mucosal candidiasis; Jones-Carson J et al.; Despite the prevalence of gamma delta T cells in mucosae that are typically colonized by Candida albicans, little is known of the possible role of these cells in resistance to candidiasis . A sharp increase in the number of gamma delta T cells and macrophages following intraperitoneal inoculation of mice with C . albicans led us to examine the role of these cells in the immune response to C . albicans . We show that the gamma delta T cells enhance macrophage nitric oxide (NO) production and anti-candida activity, in vitro . We also propose that the gamma delta T cells regulate macrophage function during candidiasis in vivo as well, because depletion of these cells abrogated inducible NO synthase expression in mucosae and enhanced murine susceptibility to candidiasis. FEMS Immunol Med Microbiol, 1995 Jun, 11(3), 157 - 62 Nitric oxide-dependent killing of Candida albicans by murine peritoneal cells during an experimental infection; Rementeria A et al.; The phagocytic and candidacidal activities of the peritoneal cells of Candida albicans-infected mice were studied 20 days following experimental infection . Both activities were enhanced during infection . The production of nitric oxide (NO) by the peritoneal cells of infected mice was determined, and an increase in the nitrite concentration in supernatants of peritoneal cell cultures was detected . The period of NO production by the peritoneal cells coincided partially with the period of enhanced C . albicans killing . The inhibition of NO synthesis by N-monomethyl-L-arginine was concomitant with inhibition of candidacidal activity . We conclude that NO synthesis is the primary candidacidal mechanism of the murine peritoneal cells activated by C . albicans infection. J Hosp Infect, 1995 Jun, 30 Suppl, 209 - 17 Infections in liver transplantation: risk factors and strategies for prevention; Kibbler CC; Infection affects up to 70% of liver transplant recipients and is the second most common complication after rejection and graft dysfunction . Identified risk factors for infection include: previous transplantation; type of biliary anastomosis; transfusion requirements at surgery; surgical complications; duration of operation; duration of postoperative ventilation; serological status of donor and recipient; steroid use and serotherapy for rejection; and pre- and post-transplant antibiotic usage . The majority of symptomatic infections are bacterial and relate to surgery (intra-abdominal, biliary and wound infections), ventilation and intravenous cannulae . Cytomegalovirus infections occur in 45-100% of recipients but are asymptomatic in the majority . Fungal infections are mostly due to Candida albicans but infections due to Aspergillus spp . occur in approximately 6% and carry a high mortality . There are very few prospective comparative trials of antimicrobial prophylaxis in this patient population . The management of these patients needs to be based on such studies. J Antimicrob Chemother, 1995 Jun, 35(6), 793 - 804 Correlation of in-vitro susceptibility test results with clinical response: a study of azole therapy in AIDS patients; Rodriguez-Tudela JL et al.; The in-vitro susceptibilities of 40 clinical isolates of Candida albicans to ketoconazole and fluconazole were determined and an attempt was made to correlate these data with the clinical responses of the patients from whom the strains were originally isolated to treatment with these agents . Of 40 patients with the acquired immunodeficiency syndrome (AIDS) with oropharyngeal and/or oesophageal candidosis, 21 received ketoconazole and 19 fluconazole . Susceptibility testing was performed by a microbroth dilution method with RPMI-2% glucose medium according to the recommendations of the National Committee for Clinical Laboratory Standards; growth inhibition was estimated spectrophotometrically and the MIC endpoint was defined in terms of the IC1/2 . The MICs of 236 additional strains of C . albicans, which were also isolated from AIDS patients, were used to establish a susceptibility profile for this species . On the basis of the susceptibility test results and the clinical responses of the 40 patients, the following tentative breakpoints for ketoconazole and fluconazole are proposed: patients with infections caused by C . albicans strains with MICs of ketoconazole and fluconazole or < or = 0.001 and < or = 0.25 mg/L respectively would be expected to respond to treatment with these agents and isolates with MICs which meet these criteria are therefore classified as susceptible; patients with infections caused by strains with MICs of ketoconazole and fluconazole of > or = 0.06 and > or = 16.0 mg/L respectively would not be expected to respond to treatment with these agents and isolates with MICs which meet these criteria are therefore classified as resistant; the response of patients with infections caused by strains with MICs of ketoconazole and fluconazole of 0.003-0.03 and 0.5-8.0 mg/L respectively cannot be reliably predicted and isolates with MICs which fall within these ranges are therefore classified as being of indeterminate susceptibility . The present study demonstrates that the results of in-vitro susceptibility testing with RPMI-2% glucose broth correlate with the clinical response to therapy and can be used to facilitate optimal treatment in AIDS patients with oropharyngeal and/or oesophageal candidosis. J Antimicrob Chemother, 1995 Jun, 35(6), 739 - 49 Defining conditions for microbroth antifungal susceptibility tests: influence of RPMI and RPMI-2% glucose on the selection of endpoint criteria; Rodriguez-Tudela JL et al.; We have compared amphotericin B, flucytosine, ketoconazole and fluconazole susceptibilities of 40 clinical isolates of Candida albicans by broth microdilution in two different media: RPMI 1640 (RPMI) and the same medium supplemented with 18 g of glucose per L (RPMI-2% glucose) . Preparation of media, drugs and inocula, as well as incubation temperature, followed the recommendations of the National Committee for Clinical Laboratory Standards (Villanova, PA, USA) antifungal agent working group for broth macrodilution tests with antifungal agents . Microtitre plates were agitated for 5 min before spectrophotometric readings were performed with an automatic plate reader . MIC endpoints were defined in three different ways: (i) MIC-100% for amphotericin B and flucytosine; (ii) MIC-80% for azole-drugs and also for flucytosine; (iii) IC1/2 for azole-drugs . The MIC endpoints were compared between the two different media in order to ascertain which was the best criterion . For amphotericin B, 100% of strains had a maximum difference of a twofold dilution in both media . For flucytosine, MIC values were very similar in both media, irrespective of the MIC endpoint chosen, MIC-100% or MIC-80% . For azole-drugs the (MIC-80%)50 and (MIC-80%)90 in RPMI were higher than those in RPMI-2% glucose . However, (IC1/2)50 and (IC1/2)90 were identical in both media as well as (MIC-80%)50 and (MIC-80%)90 in RPMI-2% glucose, The limited growth of yeasts in RPMI precludes the selection of an azole-MIC-80% endpoint, although the MIC determination was performed with an objective turbidimetric method (spectrophotometric reading plus mathematical MIC calculation) . The use of RPMI-2% glucose produces the same MIC whatever methods was used, IC1/2 or MIC-80% . However, some minor discrepancies can be expected between IC1/2 and MIC-80% when strains with higher "trailing effect" are being tested . Therefore, we recommended IC1/2 in RPMI-2% glucose as the method of choice for MIC calculation, until more studies correlating in-vitro results with clinical outcome have been performed. Biol Pharm Bull, 1995 Jun, 18(6), 923 - 5 Bioactivity of nickel(II) complex containing N-glycosides derived from D-glucosamine and ethylenediamine against pathogenic yeast, Candida albicans; Yano S et al.; A nickel(II) complex containing N-glycosides derived from the reaction of D-glucosamine (D-GlcN) and ethylenediamine (en) {Ni(D-GlcN-en)2}Cl2.H20 showed effective antifungal activity against pathogenic yeast, Candida albicans, where the MIC (minimal concentration of inhibition) value of the complex is 0.25 mM. Clin Exp Allergy, 1995 Jun, 25(6), 529 - 35 Characterization of IgE-binding epitopes on Candida albicans enolase; Ito K et al.; Candida albicans enolase is one of the important allergens in Candida allergy . We isolated and purified 46kDa C . albicans enolase (CAE) from C . albicans and characterized epitopes for IgE antibody by lectin-blotting and enzymatic digestion followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting . Lectin blotting and deglycozilation indicated that this protein did not contain polysaccharide side chains . The purified CAE and recombinant fusion protein produced from CAE gene possessed common epitopes for IgE antibody . We estimated IgE binding epitopes on the basis of reported amino acid sequences from the analysis of cDNA encoding CAE . V8 protease digestion of CAE gave six polypeptide fragments (A-F) . The N-termini of each fragment were confirmed by amino acid sequence and the C-termini were estimated by molecular weights of each fragment and the specific cutting site of V8 protease . Fragment C (25.0 kDa; F-171-I-399) reacted to 90% IgE antibodies examined, whereas fragments D (21.0 kDa; F-171-I-360), E (16.2 kDa; F-171-D-317) and F (13.0 kDa; A-47-E-170) showed no IgE binding . Our results suggest that epitopes for IgE antibodies exist near the C-terminal of the protein. J Infect Dis, 1995 Jun, 171(6), 1668 - 71 Preliminary assessment of a human recombinant antibody fragment to hsp90 in murine invasive candidiasis; Matthews R et al.; Seroconversion to hsp90 is associated with recovery from systemic candidiasis in humans, and a murine monoclonal antibody to this hsp90 antigen (LKVIRK epitope) was protective in mice . A human recombinant antibody to the same epitope was assessed in acute and chronic models of murine invasive candidiasis . Lethal intravenous challenge with fluconazole-susceptible (strain 4) or fluconazole-resistant (strain 019) Candida albicans, followed 2 h later by a single dose of recombinant antibody, was associated with a statistically significant drop in mortality of > or = 40% (two experiments in BALB/c mice given strain 4; one experiment in CD-1 mice given strain 019) or 23% (BALB/c mice, strain 019) . In mice sublethally infected with strain 4, treatment with recombinant antibody was associated with improved renal clearance of infection . Antibody-mediated protection may involve neutralization of the protein-binding properties of circulating candidal hsp90, since LKVIRK strongly bound dexamethasone in vitro. Med Hypotheses, 1995 Jun, 44(6), 507 - 15 Chronic intestinal candidiasis as a possible etiological factor in the chronic fatigue syndrome; Cater RE 2nd; The chronic candidiasis syndrome, also known as the Candida-related complex, putatively caused by the overgrowth of Candida albicans in the gastrointestinal tract and secondarily in the genital organs, is briefly described . Patients with this disorder have many of the same symptoms as those with the chronic fatigue syndrome, except for the recurrent flu-like symptoms of the latter disorder . The positive response of a large number of patients with the chronic fatigue syndrome (CFS) to an oral antifungal agent and a diet for intestinal candidiasis has been described by another clinician . There is evidence that Candida albicans infection of the mucous membranes depresses T cell and natural killer (NK) cell function . Similar abnormalities of immune function are found in the CFS . The function of cytotoxic T cells, T helper cells, and NK cells is important in preventing reactivation of infections from Epstein-Barr virus, cytomegalovirus, and other herpesviruses . Reactivation of one or more of these viruses could lead to the expression of the flu-like symptoms in the CFS . Yet the immune dysfunction found in this disorder has been considered the primary underlying causal factor . It is proposed that chronic intestinal candidiasis may be an agent which leads to immune depression in many CFS patients and therefore that it could be a causal factor in CFS. FEMS Microbiol Lett, 1995 May 15, 128(3), 271 - 7 Glucosylation of cell wall proteins in regenerating spheroplasts of Candida albicans; Kapteyn JC et al.; The cell wall of Candida albicans contains mannoproteins that are covalently associated with beta-1,6-glucan . When spheroplasts were allowed to regenerate a new cell wall, initially non-glucosylated cell wall proteins accumulated in the medium . While the spheroplasts became osmotically stable, beta-1,6-glucosylated proteins could be identified in their cell wall by SDS-extraction or beta-1,3-glucanase digestion . At later stages of regeneration, beta-1,3-glucosylated proteins were also found . Hence, incorporation of proteins into the cell wall is accompanied by extracellular coupling to beta-1,6-/beta-1,3-glucan . The SDS-extractable glucosylated proteins probably represent degradation products of wall proteins rather than their precursors . Tunicamycin delayed, but did not prevent the formation of beta-1,6-glucosylated proteins, demonstrating that beta-1,6-glucan is not attached to N-glycosidic side-chains of wall proteins. J Immunol, 1995 May 15, 154(10), 5273 - 81 Growth inhibition of Candida albicans hyphae by CD8+ lymphocytes; Beno DW et al.; We have shown previously that IL-2-activated splenocytes can inhibit the growth of Candida albicans hyphae in vitro . Herein we demonstrate that plastic nonadherent lymphocytes that are CD8+ mediate the antifungal activity . Enrichment for CD8+ cells markedly enhanced the antifungal activity of the IL-2-activated lymphocyte population for C . albicans and the cytotoxic activity of the lymphocytes for an NK-resistant cell line . Depletion of CD8+ cells reduced the lymphocyte population's antifungal activity and cytotoxic activity for the NK-resistant cell line . Enrichment for NK1.1+ cells markedly reduced the antifungal activity of the lymphocyte population for C . albicans and increased the cytotoxic activity of the lymphocytes for an NK-sensitive cell line . Depletion of NK1.1+ cells increased the lymphocyte population's antifungal activity and cytotoxic activity for the NK-resistant cell line . Generation of the antifungal lymphocytes in culture required IL-2 and was not replaced with IFN-gamma . These data show that IL-2-activated CD8+ T lymphocytes exert the greatest amount of antifungal effect against the hyphal form of C . albicans, whereas IL-2- or IFN-gamma-activated NK cells have little or no effect against the hyphae. Eur J Biochem, 1995 May 15, 230(1), 111 - 8 Selenomethionine labelling of phosphomannose isomerase changes its kinetic properties; Bernard AR et al.; Phosphomannose isomerase (PMI) is an essential enzyme in the early steps of the protein glycosylation pathway in both prokaryotes and eukaryotes . Lack of the enzyme is lethal for fungal organisms and it is thus a potential fungicidal target . To facilitate the solution of the three-dimensional structure of the enzyme from the pathogen Candida albicans, we have produced the recombinant selenomethionine-labelled enzyme (SeMet-PMI) . DL41, a methionine auxotroph Escherichia coli strain, was transformed with a PMI expression plasmid and grown on an enriched selenomethionine-containing medium to high-cell densities . The SeMet-PMI protein has been purified and found by amino acid analysis to have its methionine residues replaced by selenomethionine residues . Electrospray mass spectroscopy showed a major species of 49,063 +/- 10 Da for SeMet-PMI compared to 48,735 +/- 6 Da for the normal recombinant enzyme, accounting for the incorporation of seven selenomethionine residues . SeMet-PMI crystallised isomorphously with the normal PMI protein and the crystals diffract to 0.23 nm . Kinetic characterisation of SeMet-PMI showed that its Km for the substrate mannose-6-phosphate was fourfold higher than that of its methionine-containing counterpart . The inhibition constant for zinc ions was also increased by a similar factor . However, the Vmax was unaltered . These results suggested that one or more methionine residues must be in close proximity to the substrate-binding pocket in the active site, rendering substrate access more difficult compared to the normal enzyme . This hypothesis was confirmed by the finding of four methionine residues lying along one wall of the active site. Nucleic Acids Res, 1995 May 11, 23(9), 1481 - 6 The CUG codon is decoded in vivo as serine and not leucine in Candida albicans; Santos MA et al.; Previous studies have shown that the yeast Candida albicans encodes a unique seryl-tRNA(CAG) that should decode the leucine codon CUG as serine . However, in vitro translation of several different CUG-containing mRNAs in the presence of this unusual seryl-tRNA(CAG) result in an apparent increase in the molecular weight of the encoded polypeptides as judged by SDS-PAGE even though the molecular weight of serine is lower than that of leucine . A possible explanation for this altered electrophoretic mobility is that the CUG codon is decoded as modified serine in vitro . To elucidate the nature of CUG decoding in vivo, a reporter system based on the C . albicans gene (RBP1) encoding rapamycin-binding protein (RBP), coupled to the promoter of the C . albicans TEF3 gene, was utilized . Sequencing and mass-spectrometry analysis of the recombinant RBP expressed in C . albicans demonstrated that the CUG codon was decoded exclusively as serine while the related CUU codon was translated as leucine . A database search revealed that 32 out of the 65 C . albicans gene sequences available have CUG codons in their open reading frames . The CUG-containing genes do not belong to any particular gene family . Thus the amino acid specified by the CUG codon has been reassigned within the mRNAs of C . albicans . We argue here that this unique genetic code change in cellular mRNAs cannot be explained by the 'Codon Reassignment Theory'. J Biochem (Tokyo), 1995 May, 117(5), 1131 - 7 A novel big defensin identified in horseshoe crab hemocytes: isolation, amino acid sequence, and antibacterial activity; Saito T et al.; Hemocytes of the horseshoe crab (limulus) contain a family of arthropodous peptide antibiotics, termed the tachyplesin family, and antibacterial protein, called anti-LPS factor, of which the former is located in the small (S) granules and the latter in the large (L) granules of the hemocytes . In our ongoing studies on granular components, we have identified here a novel defensin-like substance present in both L- and S-granules . This substance strongly inhibits the growth of Gram-negative and -positive bacteria, and fungi, such as Candida albicans . The isolated substance, tentatively termed "big defensin," consists of 79 amino acid residues, of which the COOH-terminal 37 residues have a sequence similar to those of mammalian neutrophil-derived defensins, especially rat defensin . Characterization of the disulfide motif in big defensin indicated that the disulfide array is identical to that of beta-defensins from bovine neutrophils . One clear structural difference is that the limulus hemocyte-derived big defensin has an extension of the NH2-terminal hydrophobic sequence with 35 amino acid residues followed by the COOH-terminal cationic defensin portion . This amphipathic nature of big defensin seems likely to be associated with its potent antibacterial activity . Furthermore, antibacterial activities of the NH2-terminal hydrophobic region and the COOH-terminal defensin portion separated by tryptic digestion are significantly different: the former displays a more potent activity against Gram-positive bacteria, whereas the latter is more potent against Gram-negative bacteria . Big defensin, therefore, may prove to represent a new class of defensin family possessing two functional domains with different antimicrobial activities. Gen Diagn Pathol, 1995 May, 141(1), 35 - 9 Neuropathologic findings after organ transplantation . An autopsy study; Schwechheimer K et al.; Since 1972 organ transplantations of kidney, bone marrow, liver, heart and lung have been performed at the University Hospital of Essen, Germany . Out of 2535 transplantations until September 1993, autopsies were performed in 157 patients In 25 patients (15.9%) neuropathologic findings (n = 26) were found . In 97 autopsies after bone marrow transplantation, 9 patients (9.3%) exhibited a severe neuropathologic alteration . In six patients (6/9; 66.6%), necrotisizing toxoplasmose encephalitis was found . Other cases showed a septic-metastatic mycotic encephalitis with crypto-coccus neoformans and candida albicans (n = 2) and leucemia infiltrates (n = 1) . Massive cerebral hemorrhage was the most frequent neuropathologic finding after liver (4/8) and kidney transplantation (3/6) . In addition liver-transplanted patients exhibited septic-metastatic encephalitis (3/8) and embolic brain infarct (1/8) as well as cerebral metastases (2/6) and primary malignant cerebral lymphoma in kidney transplantation (1/6) . CNS findings in five autopsies after heart-lung-transplantation were diverse . They comprised intracerebral hemorrhage, intravasal lymphoma and septic-metastatic encephalitis, respectively . In summary, neuropathologic autopsy findings after organ transplantation are diverse and preferentially comprise infections, cerebral hemorrhages, and malignant lymphomas . After bone marrow transplantation, the most frequent neuropathologic autopsy finding was toxoplasmose encephalitis and massive cerebral hemorrhages after liver and kidney transplantations. Mycoses, 1995 May-Jun, 38(5-6), 235 - 7 The aetiological agents of superficial cutaneous mycoses in Jos, Plateau State of Nigeria; Ayanbimpe GH et al.; A survey of superficial skin mycoses was carried out among miners and office workers employed in different establishments in Jos, Nigeria . Mycotic infection was demonstrable by microscopy and culture in 45 (10.4%) subjects: 20 males and 25 females . Malassezia furfur was the predominant aetiological agent, followed by Candida albicans and Trichophyton soudanense . Other aetiological agents frequently recovered were T . rubrum., T . mentagrophytes., Microsporum audouinii and Trichosporon beigelii. Mycoses, 1995 May-Jun, 38(5-6), 191 - 5 Preliminary studies of the antifungal activities of some medicinal plants against Basidiobolus and some other pathogenic fungi; Nwosu MO et al.; The antifungal activities of extracts of 10 medicinal plants collected from south-eastern parts of Nigeria were tested against seven pathogenic fungi using the broth dilution and agar plate methods . All the extracts at 1:10 dilution inhibited the growth of Basidiobolus haptosporus and B . ranarum but did not inhibit that of Aspergillus fumigatus, Geotrichum candidum and Candida albicans . While extracts from Piper guineense, Ocimum gratissimum, Moringa oleifera and Erythrophleum suaveolens inhibited the growth of Trichophyton rubrum and T . mentagrophytes, those from Fatropha curcas, Mitracarpus villosus, Azadirachta indica and Gongronema latifolium failed to do so at 1:10 dilution . Extract from Piper sp . was also able to inhibit the growth of B . haptosporus at a concentration as low as 1:80 dilution followed by those of Ocimum and Rauvolfia spp . at 1:40 dilution . These results indicate possible use of certain plant extracts in the treatment of subcutaneous phycomycosis in humans and animals. Neurosurgery, 1995 May, 36(5), 1009 - 12; discussion 1012-3 Candidal pituitary abscess: case report; Heary RF et al.; We report a case of a culture-proven intrasellar Candida albicans abscess . A 36-year-old woman presented with a history of headaches, menstrual irregularities, and mild symptoms of diabetes insipidus . She was neurologically intact at the time of a transsphenoidal surgery for a presumed pituitary adenoma . An extensive work-up revealed that although the patient was seronegative for human immunodeficiency virus, she was immunocompromised with a T-cell dysfunction . Fungal abscesses of the pituitary gland have rarely been reported . This is the first documented case of a patient who is seronegative for human immunodeficiency virus who becomes infected by an ordinarily innocuous fungus, Candida albicans. J Dent Res, 1995 May, 74(5), 1152 - 61 Oral Candida: clearance, colonization, or candidiasis? Cannon RD, Holmes AR, Mason AB, Monk BC. Candida albicans is frequently isolated from the human mouth, yet few carriers develop clinical signs of candidiasis . Oral candidiasis presents clinically in many forms . This reflects the ability of the yeast to colonize different oral surfaces and the variety of factors which predispose the host to Candida colonization and subsequent infection . Colonization of the oral cavity appears to be facilitated by several specific adherence interactions between C . albicans and oral surfaces which enable the yeast to resist host clearance mechanisms . Thus, Candida has been shown to adhere to complement receptors, various extracellular matrix proteins, and specific sugar residues displayed on host or bacterial surfaces in the oral cavity . Oral candidiasis results from yeast overgrowth and penetration of the oral tissues when the host's physical and immunological defenses have been undermined . Tissue invasion may be assisted by secreted hydrolytic enzymes, hyphal formation, and contact sensing . While these and other phenotypic characteristics may endow certain Candida species or strains with a competitive advantage in the oral cavity, it is the host's immune competence that ultimately determines whether clearance, colonization, or candidiasis occurs. Microbiology, 1995 May, 141 ( Pt 5), 1147 - 56 Cloning of a Candida albicans peptide transport gene; Basrai MA et al.; A Candida albicans peptide transport gene, CaPTR2, was cloned from a C . albicans genomic library by functional complementation of a peptide transport deficient mutant (strain ptr2-2) of Saccharomyces cerevisiae . CaPTR2 restored peptide transport to transformants as determined by uptake of radiolabelled dileucine, growth on dipeptides as sources of required amino acids, and restoration of growth inhibition by toxic peptides . Plasmid curing experiments demonstrated that the peptide transport phenotype was plasmid borne . CaPTR2 was localized to chromosome R of C . albicans by contour-clamped homologous electric field gel chromosome blots . Deletion subclones and frameshift mutagenesis were used to narrow the peptide transport complementing region to a 5.1 kb DNA fragment . DNA sequencing of the complementing region identified an ORF of 1869 bp containing an 84 nucleotide intron . The deduced amino acid sequence predicts a protein of 70 kDa consisting of 623 amino acids with 12 hydrophobic segments . A high level of identity was found between the predicted protein and peptide transport proteins of S . cerevisiae and Arabidopsis thaliana . This study represents the first steps in the genetic characterization of peptide transport in C . albicans and initiates a molecular approach for the study of drug delivery against this pathogen. J Toxicol Environ Health, 1995 May, 45(1), 75 - 82 Effects of exposure to NO2 or SO2 on bronchopulmonary reaction induced by Candida albicans in guinea pigs; Kitabatake M et al.; The effects of NO2 or SO2 on the bronchopulmonary reactions induced by Candida albicans in guinea pigs were evaluated . Thirty-six guinea pigs (3 groups of 12 animals each) were sensitized with intraperitoneal injection of 10 mg of C . albicans, given twice . Two groups of animals were exposed to about 5 ppm of NO2 or SO2 for 4 h/d, 5 d/wk; this exposure was conducted a total of 30 times during the study . The third group served as the control and was not exposed to these pollutants . Two weeks after the second sensitization, all the animals were subjected to inhalation exposure to C . albicans . For 42 h after the antigen challenge, the respiratory rates and expiration/inspiration ratios of the animals were automatically monitored . The number of animals showing tachypnea was significantly higher in the NO2 exposure group than in the control from 15 h after antigen challenge . In the SO2 exposure group, the number of animals showing prolonged expiration or prolonged inspiration, or both, was significantly higher than that in the control group, and the symptoms were observed from approximately 15 h after antigen challenge . These findings showed that delayed-type dyspneic symptoms in guinea pigs were increased by exposure to NO2 or SO2, although the symptoms and degree of dyspnea were different for the two gases. J Med Microbiol, 1995 May, 42(5), 372 - 9 The genotypic relationship of Candida albicans strains isolated from the oral cavity of patients with denture stomatitis; Mathaba LT et al.; Fifty-seven isolates of Candida albicans were obtained from different sites within the oral cavities of 18 dental patients without AIDS or any malignancies . Eleven of the patients had oral candidosis associated with the wearing of dentures . The genotypic relationships of the individual isolates were determined by hybridisation of a C . albicans-specific moderately repetitive sequence, 27A, to EcoRI-digested C . albicans chromosomal DNA . From the DNA profiles, the isolates could be divided into 22 distinct genetic groups . In the majority of patients, a single unique strain of C . albicans appeared to dominate in the oral cavity . Re-infection following antifungal therapy was generally due to the re-emergence of the original infecting strain . The C . albicans strains isolated from dental plates did not form a distinct genetic group . These results suggest that denture stomatitis is due to the outgrowth of commensal strains of C . albicans. J Infect Dis, 1995 May, 171(5), 1289 - 94 Resistance of zinc-supplemented Candida albicans cells to the growth inhibitory effect of calprotectin; Santhanagopalan V et al.; Calprotectin is a neutrophil cytoplasmic protein with significant microbistatic activity . This protein may compete for zinc, or the metal may inactivate a different microbistatic activity of the protein . To distinguish between these possibilities, the sensitivity to calprotectin was determined for zinc-supplemented Candida albicans cells . The latter had increased growth in cultures containing either human empyema fluid as a source of calprotectin or purified calprotectin itself . This increased growth did not appear to be due to leakage of zinc into the medium . In other experiments, empyema fluid supernatants did not suppress C . albicans growth across a dialysis membrane; however, other studies suggested that it is difficult to significantly suppress C . albicans growth by zinc depletion unless the depleting agent remains in the cultures . These results indicate that calprotectin inhibits C . albicans growth through competition for zinc. J Bacteriol, 1995 May, 177(10), 2953 - 5 The "universal" leucine codon CTG in the secreted aspartyl proteinase 1 (SAP1) gene of Candida albicans encodes a serine in vivo; White TC et al.; A number of Candida species possess a tRNA(Ser)-like species that recognizes CTG codons that normally specify leucine (Leu) in the universal code of codon usage . Mass spectrometry and Edman sequencing of peptides from the secreted aspartyl proteinase isoenzyme (Sap1) demonstrate that positions specified by the CTG codon contain a nonmodified serine (Ser) in Candida albicans. EMBO J, 1995 May 1, 14(9), 1932 - 41 Lymphoproliferative disorder and imbalanced T-helper response in C/EBP beta-deficient mice; Screpanti I et al.; C/EBP beta is considered a key element of interleukin-6 (IL-6) signalling as well as an important transcriptional regulator of the IL-6 gene itself . We describe here how mice lacking C/EBP beta develop a pathology similar to mice overexpressing IL-6 and nearly identical to multicentric Castleman's disease in human patients, with marked splenomegaly, peripheral lymphadenopathy and enhanced haemopoiesis . Humoral, innate and cellular immunity are also profoundly distorted, as shown by the defective activation of splenic macrophages, the strong impairement of IL-12 production, the increased susceptibility to Candida albicans infection and the altered T-helper function . Our data show that C/EBP beta is crucial for the correct functional regulation and homeostatic control of haemopoietic and lymphoid compartments. Cell Immunol, 1995 May, 162(2), 256 - 64 Cytokine response to inactivated Candida albicans in mice; Rosati E et al.; Inactivated Candida albicans (CA) cells induce strong activation of natural cytotoxic effectors in mice . In the present study we examined the expression of cytokine genes involved in the immune response to CA . It has been reported that differential cytokine production by natural immune cells is important for regulating the development of specific TH response . Northern blot analysis was performed on peritoneal exudate cells (PEC) recovered from CD2F1 mice injected ip with five doses of CA (CA-5d, on Days -14, -10, -7, -3, 0 with respect to the in vitro assays at 2, 24, and 72 hr) or from mice injected ip with four doses of CA (CA-4d, on Days -14, -10, -7, -3 with respect to the in vitro assay on Day 0) . On Day 0, before the fifth CA injection, PEC expressed a high level of IL-2 and a low level of IL-1 beta mRNAs while genes coding for IL-4, IL-5, IL-6, IL-10, IL-12, TNF alpha, and IFN gamma were not expressed and there was a high level of NK activity . Two hours after CA-5d a high level of IFN gamma and a low level of IL-10 mRNAs were already evident, while IL-2 and much more IL-1 beta had greatly increased . IL-6, TNF alpha, and IL-2R alpha chain mRNAs were also detectable, whereas IL-4, IL-5, and IL-12 were not expressed . IL-12 mRNA was also absent in earlier stages of the CA sensitization . Both cellularity and NK activity of peritoneal exudate had increased with respect to Day 0 . At 24 hr whereas IL-2 mRNA remained high, both IL-1 beta and IFN gamma mRNAs expression had decreased . Expression of other cytokines was no longer detectable but NK activity remained high and a significant LAK activity was also induced . After 72 hr, while the IL-2 mRNA level and NK activity were still high the IL-1 beta mRNA expression had further decreased . These results indicate that CA induces a predominant production of IFN gamma and IL-2, cytokines involved in the development of TH1 response but it is unable to induce IL-12 . This secondary pathway, without IL-12 involvement in the development of TH1 response, is probably the result of the ability of IL-2, IL-1 beta, and TNF alpha to synergize in inducing IFN gamma synthesis by NK cells. Infect Immun, 1995 May, 63(5), 1993 - 8 Evidence implicating phospholipase as a virulence factor of Candida albicans; Ibrahim AS et al.; Three different approaches were used to investigate the role of extracellular phospholipases in the pathogenicity of Candida albicans . First, we compared 11 blood isolates of this yeast with an equal number of commensal strains isolated from the oral cavities of healthy volunteers . Blood isolates produced significantly more extracellular phospholipase activity than the commensal strains did . Second, two clinical isolates of C . albicans that differed in their levels of virulence in a newborn mouse model were compared for their ability to secrete phospholipases . The invasive strain produced significantly more extracellular phospholipase activity than the noninvasive strain did . Third, nine blood isolates were characterized for their phospholipase and proteinase production, germ tube formation, growth, and adherence to and damage of endothelial cells in vitro . These factors were analyzed subsequently to determine whether they predicted mortality in a mouse model of hematogenously disseminated candidiasis . By proportional hazard analysis, the relative risk of death was 5.6-fold higher (95% confidence interval, 1.672 to 18.84 {P < 0.005}) in the mice infected with the higher-phospholipase-secreting strains than in the low-phospholipase secretors . None of the other putative virulence factors predicted mortality . Characterization of phospholipases secreted by three of the blood isolates showed that these strains secreted both phospholipase B and lysophospholipase-transacylase activities . These results implicate extracellular phospholipase as a virulence factor in the pathogenesis of hematogenous infections caused by C . albicans. Infect Immun, 1995 May, 63(5), 1887 - 92 Expression of Candida albicans SAP1 and SAP2 in experimental vaginitis; De Bernardis F et al.; Several strains of Candida albicans were compared for their ability to cause vaginal infection in a rat model, and their vaginopathic potentials were correlated with the expression of two aspartyl proteinases genes (SAP1 and SAP2) and adherence in vivo to the vaginal epithelium . Dot blot reactions and Northern blot analysis with RNA extracted from the vaginal fluid of rats infected with the highly vaginopathic strains H12 and 10261 demonstrated the expression of both SAP1 and SAP2 during the first week of infection . In contrast, neither gene was expressed during infection by a nonvaginopathic strain (N), even though the organism could be recovered during the first 24 h postinfection . A moderately vaginopathic strain (P) also expressed both genes, but the level of SAP1 mRNA appeared to decrease prior to that of SAP2 . Neither gene was expressed, even by the highly vaginopathic strains, after the first week of infection, concomitant with a decrease in the number of organisms recovered from the vaginas . Analysis of in vivo adherence showed that the nonvaginopathic strain (N) adhered to vaginal epithelial cells less readily than the highly vaginopathic strain (H12) and moderately vaginopathic strain (P) . Thus, in addition to its inability to express SAP1 and SAP2 in vivo, the nonvaginopathic strain does not colonize host cells to the same extent as the other strains tested . Our results demonstrate the early in vivo expression of two aspartyl proteinase gene during candidal vaginitis and suggest its association with the establishment of a vaginal infection. Infect Immun, 1995 May, 63(5), 1806 - 9 Differential susceptibility of yeast and hyphal forms of Candida albicans to macrophage-derived nitrogen-containing compounds; Blasi E et al.; Candida albicans is a dimorphic fungus capable of transition from the yeast form (Y-Candida) to the hyphal form (H-Candida) . Both Y-Candida and H-Candida are known to be growth inhibited by murine macrophages (M phi) in vitro . In the present report, we demonstrate that M phi exposed to interferon gamma (IFN-gamma) plus lipopolysaccharide (LPS) show enhanced anti-Y-Candida and anti-H-Candida activities . To further investigate the phenomenon, Y-Candida and H-Candida were assessed for susceptibilities to M phi-derived supernatants . Only the growth of H-Candida, and not that of Y-Candida, is impaired by cell-free supernatants from M phi treated with IFN-gamma plus LPS . In contrast, no H-Candida growth inhibition occurs when supernatants from M phi exposed to IFN-gamma plus LPS in the presence of NG-monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthesis, are employed . Finally, supernatants from M phi incubated with sodium nitroprusside, an NO-generating agent, also show anti-H-Candida activity . In conclusion, these results indicate that H-Candida but not Y-Candida is susceptible to extracellular antifungal mechanisms employed by M phi, which likely involve stable nitrogen-containing compounds. Pediatrics, 1995 May, 95(5), 682 - 7 Invasive fungal dermatitis in the < or = 1000-gram neonate; Rowen JL et al.; OBJECTIVE . In 1991, we noted the emergence amongst our extremely low birth weight neonates of a new clinical entity, invasive fungal dermatitis, characterized by erosive, crusting lesions and a high rate of subsequent systemic fungal infection . We sought to define this condition and examine potential risk factors . METHODS . Sixteen neonates with invasive fungal dermatitis were seen during a 2-year period in three Baylor College of Medicine affiliated intensive care nurseries . Seven were confirmed cases, with skin biopsy evidence of invasion beyond the stratum corneum . Nine had a consistent clinical course and a positive potassium hydroxide examination of skin scrapings or isolation of fungi from skin or systemic cultures . Three controls were matched to each case by hospital, date of admission, and birth weight . Data was collected by retrospective chart review . RESULTS . Invasive fungal dermatitis occurred in 5.9% of at-risk infants . Case patients had a mean birth weight of 635 g and developed skin lesions at a mean age of 9 days (range, 6 to 14) . Candida albicans was the most commonly implicated pathogen, but other Candida species, Aspergillus, Trichosporon beigelii, and Curvularia were also seen . Disseminated infection occurred in 69%, all due to Candida sp . Case patients were significantly more premature than controls (mean gestation, 24.4 vs 25.9 weeks) and were more likely to be delivered vaginally (81% vs 50%) . Postnatal steroids were administered to cases (81%) more often than controls (46%) . Case patients had more prolonged hyperglycemia (as assessed by insulin administration) than controls (mean 4.3 vs 2.0 days) . CONCLUSIONS . Invasive fungal dermatitis is a disease of the smallest, most immature neonates and is associated with vaginal birth, steroid administration, and hyperglycemia . We speculate that the skin serves as a portal of entry for colonizing fungal species and may thus lead to disseminated infection . Methods to improve skin barrier function may be useful in preventing this disorder. J Med Vet Mycol, 1995 May-Jun, 33(3), 205 - 7 Molecular identification of Candida albicans; Weissman Z et al.; The benomyl resistant gene (BenR) found in Candida albicans, but not in other species of Candida, was used as a probe for the identification of C . albicans in clinical specimens . The utility of this probe to detect this species was demonstrated by Southern and dot-blot analysis, and by PCR . The possible use of this gene in C . albicans typing by the RFLP method is also demonstrated. J Med Vet Mycol, 1995 May-Jun, 33(3), 201 - 3 Highly sensitive detection of fungal antigens by ultrasound-enhanced latex agglutination; Grundy MA et al.; Treatment with ultrasound has been employed to greatly enhance the sensitivity of commercially available latex agglutination tests for fungal antigens . This 5 min procedure detects 40 pg ml-1 of Candida albicans mannan and 70 pg ml-1 of Aspergillus fumigatus galactomannan, a 250 and 500-fold improvement respectively over conventional agglutination test sensitivities . The ultrasound-enhanced test offers the possibility of improved diagnosis and management of patients with systemical candidosis or invasive aspergillosis. J Med Vet Mycol, 1995 May-Jun, 33(3), 191 - 5 Combined effect of amphotericin B and flucytosine on hyphal growth of Candida albicans estimated at a single hypha level; Oh KB et al.; The in vitro efficacy of amphotericin B and flucytosine, separately and in combination, against the hyphal growth of Candida albicans was evaluated in situ using an automatic analysing system . A colony of C . albicans was in contact with a glucose-salt medium supplemented with biotin plus calf serum (GS medium) and GS medium containing the antifungal agent, in sequence . Minimum inhibitory concentrations at single hyphal level (S-MIC) were determined based on the response that was measured . Amphotericin B S-MICs ranged from 0.8 to 0.4 microgram ml-1, and S-MIC values > 102.4 micrograms ml-1 were obtained with flucytosine when the two agents were used independently . When the two agents were used in combination, however, a synergistic interaction between the two agents at concentrations below their individual S-MICs was observed. J Interferon Cytokine Res, 1995 May, 15(5), 421 - 9 Defective expression of interferon-gamma, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and interleukin-6 in activated peripheral blood lymphocytes from glioma patients; Urbani F et al.; The ability of a mannoprotein antigen from Candida albicans (MP) or interleukin-2 (IL-2) to induce cytokines in cultures of peripheral blood mononuclear cells (PBMC) of glioma patients and healthy controls was evaluated by mRNA expression and by protein secretion . The subjects studied were all responsive to both MP and IL-2, as assayed by lymphoproliferation of PBMC cultures . In control subjects, MP and IL-2 were strong inducers of IFN-gamma, IL-1 beta, TNF-alpha, and GM-CSF mRNA expression, but only MP was able to induce considerable levels of IL-6 and IL-2 mRNA expression . In MP-activated PBMC from glioma subjects, a highly defective IFN-gamma, together with a significant reduction in TNF-alpha and GM-CSF mRNA expression, was observed . This impairment was paralleled by a decreased accumulation of IL-6 and IL-2 mRNA . The pattern of cytokine mRNAs in IL-2-activated PBMC of glioma patients confirmed the impairment of IFN-gamma mRNA expression paralleled by a reduction in IL-6, TNF-alpha and GM-CSF mRNA, compared with healthy subjects . Coherently, in PBMC cultures from glioma patients, there was a clear-cut decrease in the secretion of IL-6 and TNF-alpha and especially of IFN-gamma compared with healthy controls . No or very low levels of IL-4, IL-10, and TGF-beta 2 mRNA expression were detected in PBMC cultures of both glioma and control populations, irrespective of the activation conditions.(ABSTRACT TRUNCATED AT 250 WORDS) J R Soc Med, 1995 May, 88(5), 258 - 63 Fungal feeding-line infections: beware the eyes and teeth; Nightingale JM et al.; Twenty-four fungal feeding-line infections occurred in 17 patients during 1984-1992 . Thirteen were receiving long-term home parenteral feeding and, in them, the first infection occurred after a median of 30 months (range 1-120) continuous feeding with a line that had been in situ for a median of 20 months (range 1-37) . Four were receiving short-term feeding through a line that had been inserted 1-2 months previously . At the time of the first infection all patients were febrile and most were anaemic (15/16), however a leucocytosis was rare (three of 16) . The fungi isolated were Candida albicans(6), Candida parapsilosis(5), Candida glabrata(2), Candida guillermondii(2) and other species (2) . In 16 patients, the feeding-line was removed at the time of the first infection and no other treatment was given, and no other complications occurred in eight (50%) of these . In 11, the line was reinserted a median of 7 days after removal (range 1-11) . Four patients (24%) developed a Candida infection of the eye 1-8 weeks after the diagnosis, uveitis (2) and endophthalmitis (2) which, in one patient, led to complete blindness in one eye . Two patients had recurrent infections which began within a month of dental therapy . In one, the infections stopped after dental extractions and, in the other, after a dental clearance . An ophthalmoscopic examination should be performed in all patients with a fungal feeding-line infection . Recurrent candidal infections may have a dental origin. Immunology, 1995 May, 85(1), 153 - 9 Mannose binding protein is involved in first-line host defence: evidence from transgenic mice; Tabona P et al.; Mannose binding protein (MBP) is a calcium-dependent C-type lectin secreted by the liver which seems to be an important component of innate or natural immunity . We have investigated the effects of Candida albicans and thioglycolate injection into transgenic mice bearing the human MBP gene . The transgenes contained a 15 kb fragment of the MBP gene which included the complete coding sequence . Northern blot hybridization showed human MBP mRNA transcripts in the liver of two transgenic lines with low and high copy number respectively . Western blot analysis showed the presence in serum of human MBP which associated into the higher multimeric forms which are capable of activating complement . Enzyme-linked immunosorbent assays (ELISA) showed that serum human MBP concentrations in the transgenes (1.90 +/- 0.16 mg/l, mean +/- SEM) were about twice as high as the levels in man . The serum concentration of MBP A, which is the mouse homologue of MBP, (13.9 +/- 0.45 mg/l) was about seven times that of human MBP . Intravenous injection of Candida albicans caused the serum human MBP level to fall by more than 50% in the first hour and then slowly recover, but it did not return the initial value by 72 hr . Candida injection caused a 25% fall in serum mouse MBP A in the first hour which then rose to supranormal levels by 72 hr . Following Candida injection mouse MBP A mRNA concentrations increased over 72 hr in contrast to human MBP mRNA which remained constant in both transgenic lines . These data indicate that the human MBP gene fragment in the transgene did not include the regulatory elements of the gene . Total haemolytic complement activity and C3 concentrations also fell immediately after Candida and thioglycolate injection while the concentrations of mannose specific immunoglobulin G (IgG) and immunoglobulin M (IgM) did not fall . The data indicate that mannose binding protein plays an important role in the initial stages of defence against infection which, in this model, is quantitatively greater than that of mannose-specific IgG and IgM antibodies . Mannose binding protein is probably most important in defense of previously unexposed and non-immune hosts. J Clin Microbiol, 1995 May, 33(5), 1283 - 8 Isolation and characterization of species-specific DNA probes from Taenia solium and Taenia saginata and their use in an egg detection assay; Chapman A et al.; Cysticercosis results from ingestion of the eggs of the tapeworm Taenia solium . Reduction of the incidence of human and swine cysticercosis requires identification and treatment of individuals who carry the adult tapeworm . T . solium and Taenia saginata eggs cannot be differentiated on the basis of morphology; thus, in order to improve existing methods for the diagnosis of taeniasis, we have developed highly sensitive, species-specific DNA probes which differentiate T . solium and T . saginata . Recombinant clones containing repetitive DNA sequences which hybridize specifically with genomic DNAs from either species were isolated and characterized . T . solium-specific DNA sequences contained complete and truncated forms of a tandemly repeated 158-bp DNA sequence . An unrelated T . saginata DNA sequence was also characterized and shown to encode a portion of the mitochondrial cytochrome c oxidase I gene . T . solium- and T . saginata-specific DNA probes did not hybridize in dot blot assays either with genomic DNA from the platyhelminths Taenia hydatigena, Taenia pisiformis, Taenia taeniaeformis, Echinococcus granulosus, and Schistosoma mansoni or with genomic DNA from other eukaryotes, including Saccharomyces cerevisiae, Candida albicans, Cryptosporidium parvum, Entamoeba histolytica, Trypanosoma gambiense, Trypanosoma brucei, and Giardia lamblia, Caenorhabditis elegans, and human DNA . By using these T . solium and T . saginata DNA probes, a rapid, highly sensitive and specific dot blot assay for the detection of T . solium eggs was developed. J Clin Microbiol, 1995 May, 33(5), 1238 - 42 Molecular typing of Candida albicans in oral candidiasis: karyotype epidemiology with human immunodeficiency virus-seropositive patients in comparison with that with healthy carriers; Lupetti A et al.; Candida albicans organisms isolated from the oral cavities of healthy carriers (26 individuals) and compromised hosts (40 human immunodeficiency virus {HIV}-seropositive patients, all showing symptomatic oral candidiasis) were compared by resolving chromosome-sized DNA molecules into electrophoretic karyotypes . Seven- to 10-band electrophoretic patterns were obtained, with significant and reproducible differences in the distributions of the DNA bands . Seven distinct classes were identified and were designated type a (8 bands), type b (8 bands), type c (7 bands), type d (9 bands), type x (10 bands), type y (10 bands), and type z (9 bands) . Four of these (types a to d) were the most representative within all of the isolated strains (95.5%), and the other three (types x to z) were observed only once in three HIV-seropositive individuals (4.5%) . Only types b and c were isolated from healthy carriers, with the percentage of their isolation being 61.5 and 38.5%, respectively, while all the described karyotypes were isolated from HIV-seropositive patients, with type b being the most frequent (45%); this was followed by types c (25%), a (15%), and d (7.5%) . The prevalence of type b and c karyotypes in HIV-infected individuals, as well as in healthy carriers, suggests that commensal strains in the oral cavities of healthy individuals may become the prevalent agents of subsequent oral candidiasis in compromised hosts . However, replacement of the original, commensal strain, if there is one, cannot be excluded in a compromised host, although strain replacement may be more reasonably hypothesized for types a and d, since only these types were isolated at a relative high percentage from the oral lesions of HIV-infected individuals. J Clin Microbiol, 1995 May, 33(5), 1223 - 30 Evidence for nosocomial transmission of Candida albicans obtained by Ca3 fingerprinting; Schmid J et al.; The moderately repetitive sequence Ca3 was used to fingerprint Candida albicans isolates from 32 patients hospitalized for more than 3 days, 17 recent admissions or outpatients, and 8 recently readmitted patients and 10 commensal isolates from the community in Wellington, New Zealand, plus isolates from 21 hospitalized patients, 26 outpatients or recent admissions, 4 recently readmitted patients, and 10 healthy individuals in the community in Auckland, New Zealand . In Wellington, isolates from patients hospitalized in Wellington Hospital for more than 3 days were genetically significantly less diverse than were isolates from outpatients or recent admissions or isolates from healthy individuals in the community . In addition, two clusters of genetically similar strains were isolated from hospitalized patients significantly more often than from other individuals . These observations provide evidence (albeit indirectly) for nosocomial transmission of hospital-specific C . albicans strains . In contrast, no indication of hospital-specific transmission of C . albicans was found in Auckland Hospital . Since these results were obtained under conditions in which no candidiasis outbreak occurred in either hospital, they also suggest that Ca3 fingerprinting may be a useful tool in preventive nosocomial infection control programs, allowing assessment of the extent of C . albicans transmission occurring in a hospital. J Clin Microbiol, 1995 May, 33(5), 1129 - 35 Cluster of oral atypical Candida albicans isolates in a group of human immunodeficiency virus-positive drug users; Boerlin P et al.; Twenty-one chlamydospore-forming and germ tube-positive Candida albicans clinical isolates from 15 human immunodeficiency virus (HIV)-positive and 3 HIV-negative patients were examined by two different genetic methods . Multilocus enzyme electrophoresis and hybridization with the C . albicans-specific Ca3 probe showed that such isolates can be split into two genetically distinct groups that can be clearly distinguished . One group mainly contained strains with atypical sugar assimilation patterns and could be distinguished from the other group by the absence of intracellular beta-glucosidase activity . All 13 strains belonging to this group were isolated from the oral cavities of asymptomatic HIV-positive drug users and may be less pathogenic than the eight strains from the other group isolated either from HIV-positive patients with oropharyngeal candidiasis or from HIV-negative patients with invasive candidiasis. Arzneimittelforschung, 1995 May, 45(5), 620 - 3 Synthesis and antifungal activities of some new triazolylacetophenone derivatives; Ertan R et al.; In this study some alpha-(1,2,4-triazolyl)acetophenone derivatives were synthesized by the condensation of various triazole and alpha-bromoacetophenone rings . The structures of the compounds have been elucidated by UV, IR, 1H-NMR, mass spectra and elementary analysis . The in vitro antifungal activity of the compounds were investigated against some yeast-like fungi (Candida albicans, C . parapsilosis, C . stellatoidea and C . pseudotropicalis) and moulds such as Trichophyton rubrum and T . mentagrophytes by the tube dilution method and MIC (minimal inhibitory concentration), MFC (minimal fungicidal concentration) values were determined . Compound A16 was significantly more effective than the other compounds . The results obtained for antifungal activity against moulds were not significant. Kansenshogaku Zasshi, 1995 May, 69(5), 590 - 6 {Effect of erythromycin on macrophage functions}; Xu G et al.; Recently, it has been suggested that macrolide antibiotics act as immunomodulators . In this study, we evaluated the effect of EM on macrophage function . We used the mouse macrophage cell line, J774.1 . The following direct effects of EM on macrophage function were evaluated: chemotaxis to EM, chemokinetic effect by EM, and the effect of EM on macrophage growth . In order to examine the indirect effects of EM on macrophage functions, we preincubated macrophages with several concentrations of EM and then removed the EM . Thereafter, the phagocytosis of beads, cytocidal activity against Candida albicans, and chemotaxis to lipopolysaccharide were evaluated . EM (at the concentration between 0.04 and 0.2 microgram/ml) directly stimulated macrophage chemotaxis and chemokinesis . In addition, EM dose-dependently stimulated the growth of macrophages . EM pretreatment (for 4 hours at the contractions between 0.04 and 0.2 microgram/ml) stimulated macrophage phagocytosis, cytocidal activity against Candida albicans, and chemotaxis to lipopolysaccharide . These results suggest that EM has direct and indirect effects on macrophage functions. Kansenshogaku Zasshi, 1995 May, 69(5), 582 - 9 {Protective effect of human macrophage colony-stimulating factor on fungal infection (2) . In vitro effect of human macrophage colony-stimulating factor on systemic aspergillosis and in vitro effect on the activities of macrophage}; Fujita H et al.; We studied the protective effect of human macrophage colony-stimulating factor (M-CSF) of fungal infection due to systemic aspergillosis in normal mice . We also examined the effect of M-CSF against the activities of mouse peritoneal macrophage which were relating to the phagocytosis, the killing, the production of superoxide after contacting with phorbol myristate acetate and the production of nitric oxide after contacting with interferon-gamma in vitro . M-CSF improved the median survival time and the survival rate of systemic aspergillosis . Combination therapy with M-CSF and amphotericin-B (AMPH-B) showed the therapy with either M-CSF or AMPH-B alone . M-CSF enhanced the activities of phagocytosis and the killing of ingested Candida albicans H and spores of Aspergillus fumigatus K by macrophage . Furthermore, M-CSF promoted the production of superoxide and nitric oxide in macrophage . These results indicate that M-CSF can enhance the fungicidal activity of macrophages by activation in vivo, thereby preventing the dissemination of fungal infection. Eur J Clin Microbiol Infect Dis, 1995 May, 14(5), 406 - 11 Differential and enrichment media for selective culture and recognition of yeast species from clinical material; Louwagie B et al.; An enrichment medium was developed and evaluated for isolation of fluconazole-resistant minority yeast species in a hospital setting . The enrichment medium was made by adding fluconazole (10 micrograms/ml) to yeast nitrogen base/glucose broth . Under laboratory conditions the broth permitted detection of 20 of 20 Candida krusei isolates and 20 of 20 Candida glabrata isolates in mixtures with Candida albicans even when the Candida albicans cells outnumbered those of the other species by 1000:1 . Results of culture on the enrichment medium were compared with those obtained on routine agar media and on a yeast differential agar which facilitates detection of mixed yeast species by their colony colours . Only one Candida glabrata isolate was detected on the enrichment broth but not found on routine culture of 68 yeast-positive clinical specimens . However, bacterial over-growth in some broths may have retarded the appearance of other yeast isolates . On the yeast differential agar, 20 clinical specimens were found to contain mixtures of yeast species compared with only 2 on routine culture. Int Immunol, 1995 May, 7(5), 785 - 96 Immunoprotection against systemic candidiasis in mice; Tavares D et al.; We have previously described an immunosuppressive B cell mitogenic (ISM) protein, p43, produced by Candida albicans, which plays an important role in the survival of the microorganism in the host . The N-terminal amino acid sequence of p43 was found to be different from all amino acid sequences registered in updated protein databanks . Immunization of BALB/c mice with p43 partially neutralized the biological effects of this protein, namely depletion of bone marrow pre-B and B cells, the increased numbers of total and large B and CD4+ lymphocytes, and the non-specific polyclonal response of splenic IgG2a-, IgG2b- and IgM-secreting plaque forming cells . Immunization of BALB/c mice with p43 fully protected the mice against the fungal infection . In contrast, immunization with C . albicans sonicates (Cs) was not protective . Our data indicated that specific antibodies against p43 protected, whereas those against Cs facilitated C . albicans infection . Thus, the ratio between anti-p43 and anti-Cs antibody titres was much lower in the non-protected mice (Cs-immunized and control non-immunized) than in p43-immunized mice . Moreover, passive administration of specific anti-p43 antibodies significantly protected against fungal infection, whereas passive administration of specific anti-Cs antibodies markedly increased the susceptibility to C . albicans infection . These observations are discussed on the basis of alternative approaches of immunointervention. Biochem Mol Biol Int, 1995 May, 35(6), 1215 - 22 Status of membrane lipids and amino acid transport in morphological mutants of Candida albicans; Koul A et al.; The phospholipid composition of various morphological mutants of Candida albicans revealed a complete absence of phosphatidylinositol (PI) from plasma membranes of those cells which completely lacked mycelial growth . No other phospholipid was found to be specific to morphogenesis . The plasma membrane fractions isolated from mutants were more rigid than its wild type as was evident from their unsaturation index and fluorescence polarization measurements . The enhanced membrane rigidity of mutant cells was noted regardless whether the cells could grow only as mycelia or in their budding forms . Although some amino acids are considered to affect the morphological transition of C . albicans, this was not reflected in the transport activities of L-proline, L-alanine, L-lysine and L-glutamic acid. Pharm Res, 1995 May, 12(5), 649 - 52 Primary interactions of three quaternary ammonium compounds with blastospores of Candida albicans (MEN strain); Schep LJ et al.; The absorption of three quaternary ammonium compounds (QAC), cetylpyridinium chloride, cetrimide and benzalkonium chloride, onto the surface of blastospores of Candida albicans (MEN strain) was examined at room temperature . Equilibrium uptake occurred in less than 30 seconds for cetylpyridinium chloride and cetrimide whereas 5 min contact time was required for benzalkonium chloride . The adsorption of all three agents may be mathematically described as Langmuirian and hence a concentration-dependent formation of drug-monolayer on the surface of the blastospore occurred . From this the number of molecules adsorbed onto the surface of a single blastospore was calculated to be 1.33 x 10(12), 3.17 x 10(12) and 2.32 x 10(12) for cetylpyridinium chloride, cetrimide and benzalkonium chloride, respectively . These dissimilarities are most likely due to differences in the orientations of both the cationic nitrogen atom and the accompanying lipophilic portions of each QAC at the blastospore surface . Relating these observations to the known antiadherence effects of cetylpyridinium chloride and cetrimide, it can be concluded that monolayer coverage of the blastospore surface with QAC does not account for the observed reduced adherence . This suggests that the anti-adherence effects are due to either direct interaction with, or steric blockade of, adhesions on the blastospore surface. Yeast, 1995 Apr 15, 11(4), 301 - 10 Cloning and heterologous expression of the Candida albicans gene PMI 1 encoding phosphomannose isomerase; Smith DJ et al.; Using a DNA fragment derived from the Saccharomyces cerevisiae phosphomannose isomerase (PMI) structural gene as a probe against a random ordered array library of genomic DNA from the pathogenic fungus Candida albicans, we have cloned the C . albicans PMI 1 gene . This gene, which is unique in the C . albicans genome, can functionally complement PMI-deficient mutants of both S . cerevisiae and Escherichia coli . The DNA sequence of the PMI 1 gene predicts a protein with 64.1% identity to PMI from S . cerevisiae . Sequential gene disruption of PMI 1 produces a strain with an auxotrophic requirement for D-mannose . The heterologous expression of the PMI 1 gene at levels up to 45% of total cell protein in E . coli leads to partitioning of the enzyme between the soluble and particulate fractions . The protein produced in the soluble fraction is indistinguishable in kinetic properties from the material isolated from C . albicans cells. FEMS Microbiol Lett, 1995 Apr 15, 128(1), 95 - 100 Cloning of a DNA fragment encoding part of a 70-kDa heat shock protein of Candida albicans; Eroles P et al.; Immunoscreening of a mycelial expression library with polyclonal antibodies raised against mycelial cell wall resulted in the detection of a cDNA encoding a heat shock protein of Candida albicans . Sequence analysis of a 0.8-kb cDNA subclone, 2M-1, revealed an open reading frame encoding 244 amino acids . Southern blot analysis with this fragment as a probe demonstrated hybridization to C . albicans DNA . Northern analysis showed a substantial increase in 2M RNA expression levels after cells were subjected to heat shock . Western blot analysis with 2M monospecific antibodies recognized a 70-kDa protein which was present in membrane particles and cytosolic fractions. Cell Immunol, 1995 Apr 15, 162(1), 105 - 13 Suppression of the functional activity of IL-2-activated lymphocytes by CGRP; Wang X et al.; CGRP is a 37-amino acid neuropeptide found in the central and peripheral nervous systems as well as the nerve endings in lymphoid organs . Specific CGRP receptors are present on both T and B lymphocytes . There is increasing evidence that CGRP plays a role in regulation of the immune response . However, few investigations have examined the effects of CGRP on lymphocyte effector functions . In this report, CGRP (0.1 nM-1 microM) was shown to cause concentration-dependent inhibition of IL-2-activated lymphocyte growth inhibition of the fungus Candida albicans and cytotoxic activity for tumor cells . Maximum inhibition of lymphocyte activity by CGRP was 47.4% for the hyphae of C . albicans, 44.8% for a natural killer cell susceptible cell line, and 52.9% for a natural killer cell-resistant cell line . CGRP-mediated inhibition of lymphocyte function was mimicked by 8-bromo-cAMP (1 mM) and was correlated in a concentration-dependent manner with an increase in intracellular levels of cAMP . These increases were potentiated by pretreatment of the lymphocytes with 3-isobutyl-1-methylxanthine (0.5 mM, 10 min), an inhibitor of the cAMP phosphodiesterase . hCGRP 8-37, a selective blocker of the CGRP1 receptor, abrogated the effect of CGRP on lymphocyte function and on intracellular cAMP level elevation induced by rCGRP . CGRP had no direct effect on the capacity of IL-2-activated lymphocytes to adhere to the hyphae of C . albicans . However, both CGRP and 8-bromo-cAMP diminished the capacity of the lymphocytes to release cytoplasm