Characterization and partial purification of <Emphasis Type="Italic">Candida albicans</Emphasis> Secretory IL-12 Inhibitory Factor

Background  

We have previously shown that supernatant from Candida albicans (CA) culture contains a Secretory Interleukin (IL)-12 Inhibitory Factor (CA-SIIF), which inhibits IL-12 production by human monocytes. However, the effect of CA-SIIF on secretion of other cytokines by monocytes is unknown, and detailed characterization of this factor has not been performed.     

<Superscript>15</Superscript>N natural abundance of fossil peat reflects the influence of animal-derived nitrogen on vegetation

'¹⁵N signatures of fossil peat were used to interpret past ecosystem processes on tectonically active subantarctic Macquarie Island. By comparing past vegetation reconstructed from the fossil record with present-day vegetation analogues, our evidence strongly suggests that changes in the '¹⁵N signatures of fossil peat at this location reflect mainly past changes in the proportion of plant nitrogen derived from animal sources. Associated with uplift above sea level over the past 8,500 years, fossil records in two peat deposits on the island chronicle a change from coastal vegetation with fur and elephant seal disturbance to the existing inland herbfield. Coupled with this change are synchronous changes in the '¹⁵N signatures of peat layers. At two sites ¹⁵N-enriched peat '¹⁵N signatures of up to +17‰ were associated with a high abundance of pollen of the nitrophile Callitriche antarctica (Callitrichaceae). At one site fossil seal hair was also associated with enriched peat '¹⁵N. Less ¹⁵N enriched '¹⁵N signatures (e.g. -1.9‰ to +3.9‰) were measured in peat layers which lacked animal associated C. antarctica and Acaena spp. Interpretation of a third peat profile indicates continual occupation of a ridge site by burrowing petrels for most of the Holocene. We suggest that ¹⁵N signatures of fossil peat remained relatively stable with time once deposited, providing a significant new tool for interpreting the palaeoecology.     

Steroids excreted in urine by neonates with 21-hydroxylase deficiency: Characterization, using GC-MS and GC-MS/MS, of the D-ring and side chain structure of pregnanes and pregnenes

Steroid metabolites in urine from neonates with 21-hydroxylase deficiency are predominantly polyhydroxylated 17-hydroxyprogesterone and androgen metabolites, and most have incompletely defined structure. This study forms part of a comprehensive project to characterize and identify these in order to enhance diagnosis and to further elucidate neonatal types of steroid metabolism.Steroids were analyzed, after extraction and enzymatic conjugate hydrolysis, as methyloxime-trimethylsilyl ether derivatives on gas-chromatographs coupled to quadrupole and ion-trap mass-spectrometers. GC-MS and GC-MS/MS spectra, obtained with constant excitation conditions, were used together to determine the structure of the D-ring and the side chain of 20-oxo and 20-hydroxy pregnane(ene)s without oxo groups on the A-, B-, and C-ring.All possible combinations of D-ring and side chain configuration were considered. Most fragmentations could be interpreted as partial or complete D-ring cleavages with loss of the side chain, aided by comparison with spectra of deuterated derivatives and of borohydride reduced metabolites. Possible rearrangement ions are also discussed. More than 140 endogenous metabolites were characterized.GC-MS/MS was especially beneficial for characterization of compounds with 16,17-dihydroxy-20-oxo structure, interpreted as markers of intra-uterine enzyme induction. It also assisted the differentiation of 16-hydroxy-20-oxo metabolites, present in urine of non-affected neonates, from the diagnostic 17-hydroxy-20-oxosteroids and enabled the detection of 15,17-dihydroxy-20-oxo compounds in low concentrations. The presence of 17,21-dihydroxylated pregnane(ene)s despite the deficit in CYP21A2 is discussed.We conclude that GC-MS combined with GC-MS/MS allows reliable identification of the structure of the D-ring and side chain of pregnane(ene)s without prior isolation, even when in low concentrations in urine.     

Widespread cutaneous candidiasis and tinea infection masking mycosis fungoides

A 71-year-old female with a widespread double mycotic infection caused byC. Albicans andT. rubrum was discovered to be suffering from mycosis fungoides. Clinically she was found to have large, polycyclic erythematous plaques with scaly, slightly infiltrated borders, covering almost all areas of the glabrous skin, and also involving the scalp (with no hair penetration), the soles and palms, toe-webs, finger and toe nails; there was also perleche and oral thrush. Cultures yieldedC. albicans from most of the skin lesions, from the scalp, mouth, finger nails and urine and stool specimens, andT. rubrum from intermingled skin specimens, from the palms and soles and toe-nails. Blood culture was negative as were intracutaneous tests with fungal antigens and tuberculin. Histological examination confirmed the fungal invasion of the horny layer and at the same time revealed an underlying pathologic picture of mycosis fungoides, the lesions having been masked by the mycotic eruption. Intensive cytostatic and antifungal therapy led to a transient improvement but shortly thereafter there was a relapse of the fungal and lymphoproliferative manifestations and the patient died in septic shock.

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Résumé Une femme, agée 71 ans, ayant une double infection mycosique due àC. albicans et auT. rubrum, a été décélée qu'elle souffrait aussi d'un mycosis fungoïde. Au point de vue clinique elle avait de larges plaques érythémato-squameuses, polycicliques, aux bords légèrement infiltrés, répandues sur une grande partie de la peau glabre, paumes et plantes inclus, et affectant aussi le cuir chevelu (sans pénétration des poils), les ongles des doigts et des orteils. Les cultures ont permis d'isoler leC. albicans à partir de la majorité des lésions de la peau et du cuir chevelu, des ongles des doigts, ainsi que de la bouche, de l'urine et des selles. On a trouvé aussiT. rubrum dans des lésions cutanées entremêlées aux precedentes, dans la région palmaire et plantaire et dans les ongles des orteils. Les testes intradermiques aux antigens fongiques et à tuberculine ont été négatifs, ainsi que les hémocultures. L'examen histologique a montré l'invasion de la couche cornée par les champignons et en même temps a découvert un tableau pathologique sous-jacent d'un mycosis fungoïde, ayant été masqué par l'éruption fongique. Un traitement intensif par des produits cytostatiques et antifongiques a mené à une amélioration temporaire, mais brièvement après on a assisté à une réchute rapide des manifestations lymphoprolifératives et fongiques et la malade a décédé à la suite d'un état septique.