We report on a 28-year-old man with trisomy 7q34-qter and monosomy 15q26.3-qter caused by a paternal balanced chromosomal translocation, t(7;15)(q34;q26.3). He had bilateral congenital glaucoma (buphthalmos), as well as typical manifestations of partial trisomy 7q. To our knowledge, this is the second description of a possible relation between congenital glaucoma and 7q trisomy. He also had some Silver-Russell syndrome features, such as short stature of prenatal onset, a characteristic triangular face, clinodactyly of the fifth fingers, and body asymmetry. Fluorescence in situ hybridization analysis on his chromosomes revealed that one copy of the insulin-like growth factor 1 receptor gene (IGF1R) at 15q25-q26 was deleted, suggesting a possible role of IGF1R in the SRS phenotype.

Abnormalities, Multiple↗

PubMed2000

Estimation of minimum sterol 14alpha-demethylation-inhibitory concentration of azoles in Candida yeasts using acetate-mediated growth inhibition: potential utility in susceptibility testing.

We have recently shown that 14alpha-demethylation-deficient cells of Candida albicans are subject to growth arrest by 0.24 M acetate in a yeast extract-peptone-glucose medium and that the minimum concentration of an azole antifungal agent required for total inhibition of sterol 14alpha-demethylation (MDIC for minimum demethylation-inhibitory concentration) is practically identical to its MIC determined in the acetate-supplemented medium (O. Shimokawa and H. Nakayama, Antimicrob. Agents Chemother. 43:100-105, 1999). In the present study we estimated the MDICs of three different azoles (fluconazole, ketoconazole, and itraconazole) for strains of various Candida species using this method and compared them with the MICs determined in the corresponding acetate-free medium. The results demonstrated that the test strains were divided into two classes. One class of strains was characterized by tolerance to 14alpha-demethylation deficiency (MIC > MDIC) and consisted of strains of C. albicans, C. guilliermondii, C. kefyr, and C. tropicalis. The other class was intolerant to 14alpha-demethylation deficiency (MIC approximately MDIC) and comprised strains of C. glabrata, C. krusei, and C. parapsilosis. We also showed that replacement of the yeast extract-peptone-glucose medium with RPMI 1640 medium did not affect the results substantially. Furthermore, the 80% inhibitory concentration (IC(80)) in RPMI 1640 medium, recommended as a substitute for the conventional MIC in susceptibility testing, was found to be close to the MDIC.

Acetates↗

PubMed1999

Acetate-mediated growth inhibition in sterol 14alpha-demethylation-deficient cells of Candida albicans.

Candida albicans is a fungus thought to be viable in the presence of a deficiency in sterol 14alpha-demethylation. We showed in a strain of this species that the deficiency, caused either by a mutation or by an azole antifungal agent, made the cells susceptible to growth inhibition by acetate included in the culture medium. Studies with a mutant demonstrated that the inhibition was complete at a sodium acetate concentration of 0.24 M (20 g/liter) and was evident even at a pH of 8, the latter result indicating the involvement of acetate ions rather than the undissociated form of acetic acid. In fluconazole-treated cells, sterol profiles determined by thin-layer chromatography revealed that the minimum sterol 14alpha-demethylation-inhibitory concentrations (MDICs) of the drug, thought to be the most important parameter for clinical purposes, were practically identical in the media with and without 0.24 M acetate and were equivalent to the MIC in the acetate-supplemented medium. The acetate-mediated growth inhibition of azole-treated cells was confirmed with two additional strains of C. albicans and four different agents, suggesting the possibility of generalization. From these results, it was surmised that the acetate-containing medium may find use in azole susceptibility testing, for which there is currently no method capable of measuring MDICs directly for those fungi whose viability is not lost as a result of sterol 14alpha-demethylation deficiency. Additionally, the acetate-supplemented agar medium was found to be useful in detecting reversions from sterol 14alpha-demethylation deficiency to proficiency.

Acetates↗

PubMed1997

Inactivation of penicillin-induced staphylococcal L-forms by human serum high density lipoprotein.

In penicillin-susceptible bacteria, penicillin causes growth of a small fraction of cells as wall-deficient forms if an appropriate osmoprotection is provided (unstable L-forms). A subfraction of human serum high density lipoprotein (HDL3) was shown to have the ability to inactivate unstable L-forms of Staphylococcus aureus. The active principle was distinguishable from the well-documented trypanosome lytic factor 1 with respect to density, size, and other properties. This L-form cytotoxicity therefore seems to represent a novel antimicrobial entity in human serum.

Blood Bactericidal Activity↗

PubMed1994

Serum inhibits penicillin-induced L-form growth in Staphylococcus aureus: a note of caution on the use of serum in cultivation of bacterial L-forms.

Heat-inactivated horse serum inhibited penicillin-induced L-form colony formation in Staphylococcus aureus when included in an osmotically stabilized culture medium. Most, perhaps all, L-form colonies that appeared with low frequencies on the serum-supplemented medium were of the penicillin-independent, stable type. This relationship must be taken into account when use of serum is considered for L-form cultivation.

Blood↗

PubMed1992

Increased sensitivity of Candida albicans cells accumulating 14 alpha-methylated sterols to active oxygen: possible relevance to in vivo efficacies of azole antifungal agents.

The sensitivity of Candida albicans cells to killing by hydrogen peroxide was found to increase markedly when they were grown in the presence of sub-growth-inhibitory concentrations of the azole drug clotrimazole (CTZ). A superoxide anion-generating system consisting of xanthine and xanthine oxidase also killed such CTZ-treated cells more efficiently than control cells, but this seemed to be accounted for by hydrogen peroxide secondarily formed from superoxide anion as judged by the effect of catalase and superoxide dismutase. The increased sensitivity to hydrogen peroxide was considered to be attributable to the inhibition of 14 alpha-demethylation of ergosterol biosynthesis by CTZ, since a 14 alpha-demethylation-deficient mutant of C. albicans exhibited a similar phenotype. It is suggested that the in vivo efficacy of azole antifungal agents against C. albicans infection is at least partially due to the sensitization of the fungal cells to the oxygen-dependent microbicidal system of the phagocyte.

Antifungal Agents↗

PubMed1991

Deficient utilization of succinate in a sterol 14 alpha-demethylation mutant of Candida albicans.

Growth of a wild-type strain (KD14) started after a lag of approximately 15 h when glucose-grown cells of Candida albicans were incubated at 25 degrees C, with succinate as a sole energy/carbon source. No growth was observed, however, for a sterol 14 alpha-demethylation mutant (KD4900). During the lag period, the wild-type cells retained their respiratory activity, as measured with glucose as an added substrate, and developed the capacity to incorporate labelled succinate. In contrast, incubation with succinate for 15 h resulted in diminished respiratory activity and failed to induce the succinate uptake capacity of the mutant cells. These two differences from the wild-type seem to account for the inability of the mutant to grow in the presence of a non-fermentable substrate.

Candida albicans↗

PubMed1991

Phenotypes of Candida albicans sterol mutants deficient in delta 8,7-isomerization or 5-desaturation.

Two Candida albicans sterol mutants deficient in delta 8,7-isomerization and 5-desaturation, respectively, were studied in relation to those phenotypes associated with the 14 alpha-demethylation deficiency, i.e. repression of hypha formation, inability to grow with non-fermentable substrates, and increased sensitivity to nonpolyene-nonazole chemicals. It was found that the delta 8,7-isomerization deficiency, resulting in the accumulation of delta 8 sterols (mostly delta 24(28) or delta 5,22), was associated with severe reduction in hyphal growth and utilization of non-fermentable substrates. These cellular activities were reduced only slightly when 5-desaturation was deficient, causing the accumulation of delta 7 sterols. On the other hand, both the isomerization and desaturation deficiencies were accompanied by multiple increases in drug sensitivity which were small in magnitude compared with those associated with the 14 alpha-demethylation deficiency.

Candida albicans↗

PubMed1989

Accumulation of 14 alpha-methylergosta-8,24(28)-dien-3 beta,6 alpha-diol in 14 alpha-demethylation mutants of Candida albicans: genetic evidence for the involvement of 5-desaturase.

14 alpha-Demethylation mutants of the fungus Candida albicans have been shown to accumulate 14 alpha-methylergosta-8,24(28)-dien-3 beta,6 alpha-diol. A derivative from one of these mutants (KD4900) that does not form this 6 alpha-hydroxylated sterol but is still defective in 14 alpha-demethylation (KD4950) was obtained. Mutational restitution of 14 alpha-demethylation capacity to this derivative resulted in the formation of the 5,6-saturated sterol ergosta-7,22-dien-3 beta-ol as the major product, clearly indicating that 5-desaturase deficiency exists in this demethylation-proficient revertant (KD4952). This implies that its parent, KD4950, which has lost the ability to form the hydroxylated sterol, also is deficient in 5-desaturation. We infer from the results that 5-desaturase is responsible for the formation of the hydroxylated sterol. However, it is unclear whether the hydroxylation represents a genuine step of the normal 5-desaturation reaction.

Candida albicans↗

PubMed1989

A Candida albicans mutant conditionally defective in sterol 14 alpha-demethylation.

A conditional sterol 14 alpha-demethylation mutant of Candida albicans was isolated whose defect was dependent both on the growth temperature and on the culture medium used. Under restrictive conditions, this mutant showed a deficiency in hyphal growth and an increased susceptibility to diverse chemicals, in accordance with the phenotypes of the already known non-conditional mutants of 14 alpha-demethylation. In addition, the mutant was shown to have a conditional defect in respiration. The impaired respiration was also seen in the non-conditional mutants.

Candida albicans↗

PubMed1986

A Candida albicans rough-type mutant with increased cell surface hydrophobicity and a structural defect in the cell wall mannan.

A Candida albicans rough-type mutant showing increased hydrophobicity of the cell surface was isolated. The mutant cells contained about one-quarter as much mannan as the wild type, and were defective in antigenic factors 1, 4, 5, and 6. Acetolysis fingerprinting demonstrated that the mutant mannan had a structural defect in its carbohydrate skeleton.

Antigens, Fungal↗

PubMed1986

Accumulation of 14-methyl sterols and defective hyphal growth in Candida albicans.

Polyene-resistant mutants of Candida albicans accumulating 14-methyl sterols in place of ergosterol and defective in hyphal growth were isolated after ultraviolet mutagenesis. Analysis of revertants showed that the alteration in sterol composition, the inability to grow as hyphae, and the antibiotic resistance had returned to normal simultaneously. In addition, clotrimazole, which caused accumulation of 14-methyl sterols at a subfungistatic concentration, also inhibited hyphal formation but had little effect on yeast propagation. It is concluded that there is an intrinsic rather than a fortuitous relationship between sterol composition and morphogenesis.

Candida albicans↗

PubMed1986

Increased drug sensitivity in Candida albicans cells accumulating 14-methylated sterols.

Multiple increases in drug sensitivity were observed in Candida albicans cells that were accumulating 14-methylated sterols as a result of a mutation or clotrimazole treatment. The possibility was suggested that a change in membrane permeability caused by the alteration in sterol composition was responsible for the increased susceptibility.

Antifungal Agents↗

PubMed1984

Isolation of a Candida albicans mutant with reduced content of cell wall mannan and deficient mannan phosphorylation.

A rough-colony mutant of Candida albicans was isolated after ultraviolet mutagenesis. The mutant contained approximately half the normal amount of the cell wall mannan, the acetolysis pattern of which was indistinguishable from that of the wild-type counterpart. However, the extent of phosphorylation in the mutant mannan was about 12% of the value for wild type.

Candida albicans↗