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.

     

Coevolution of costly mate choice and condition-dependent display of good genes.

Females often choose their mates, instead of mating at random, even when a father contributes nothing but genes to his offspring. Costly female preferences for males with exaggerated traits that reduce viability, such as the peacock's tail, are particularly puzzling. Such preferences can evolve if directly favoured by natural selection or when the exaggerated trait, although maladaptive per se, indicates high overall quality of the male's genotype. Two recent analyses suggested that the advantage to mate choice based on genetic quality is too weak to explain extreme cases of exaggeration of display traits and the corresponding preferences. We studied coevolution of a female mate-preference function and a genotype-dependent male display function where mutation supplies variation in genotype quality and mate preference is costly. Preference readily evolves, often causing extreme exaggeration of the display. Mate choice and trait expression can approach an equilibrium, or a limit cycle, or exaggeration can proceed forever, eventually causing extinction.     

The CR3 motif of Rrp44p is important for interaction with the core exosome and exosome function

The 10-subunit RNA exosome is involved in a large number of diverse RNA processing and degradation events in eukaryotes. These reactions are carried out by the single catalytic subunit, Rrp44p/Dis3p, which is composed of three parts that are conserved throughout eukaryotes. The exosome is named for the 3′ to 5′ exoribonuclease activity provided by a large C-terminal region of the Rrp44p subunit that resembles other exoribonucleases. Rrp44p also contains an endoribonuclease domain. Finally, the very N-terminus of Rrp44p contains three Cys residues (CR3 motif) that are conserved in many eukaryotes but have no known function. These three conserved Cys residues cluster with a previously unrecognized conserved His residue in what resembles a metal-ion-binding site. Genetic and biochemical data show that this CR3 motif affects both endo- and exonuclease activity in vivo and both the nuclear and cytoplasmic exosome, as well as the ability of Rrp44p to associate with the other exosome subunits. These data provide the first direct evidence that the exosome-Rrp44p interaction is functionally important and also provides a molecular explanation for the functional defects when the conserved Cys residues are mutated.     

Intracellular Calcium Deficits in Drosophila Cholinergic Neurons Expressing Wild Type or FAD-Mutant Presenilin

Much of our current understanding about neurodegenerative diseases can be attributed to the study of inherited forms of these disorders. For example, mutations in the presenilin 1 and 2 genes have been linked to early onset familial forms of Alzheimer''s disease (FAD). Using the Drosophila central nervous system as a model we have investigated the role of presenilin in one of the earliest cellular defects associated with Alzheimer''s disease, intracellular calcium deregulation. We show that expression of either wild type or FAD-mutant presenilin in Drosophila CNS neurons has no impact on resting calcium levels but does give rise to deficits in intracellular calcium stores. Furthermore, we show that a loss-of-function mutation in calmodulin, a key regulator of intracellular calcium, can suppress presenilin-induced deficits in calcium stores. Our data support a model whereby presenilin plays a role in regulating intracellular calcium stores and demonstrate that Drosophila can be used to study the link between presenilin and calcium deregulation.     

Cell Cycle activation and ouabain-sensitive ion movements of 3T3 and C3H-10T½ fibroblasts

The introduction of either PGF_2α (10^?7 M) or TPA (10^?7 M) stimulated, ouabain-sensitive ⁸⁶Rb⁺ influx at 30 min in postconfluent 3T3-4 mouse fibroblast cultures by 117% and 124%, respectively. Both TPA and PGF_2α at these concentrations stimulated the incorporation of ³H-TdR into DNA. TPA had the greatest stimulatory effect, which was similar to that obtained with 10% fetal calf serum. In accord with the idea that modulation of membrane processes such as Na⁺/K⁺ pump activity in fibroblasts may reflect important events related to the initiation of DNA synthesis, it was observed that in both 3T3-4 and C3H-1 0T½ cells there were parallel increases in ³H-TdR incorporation and ouabain-sensitive ⁸⁶Rb⁺ influxes with 10^?7 M TPA, whereas PGF_2α stimulated a significant increase in ³H-TdR incorporation in 3T3-4 but not C3H-10T½ cells and only marginal increases in ouabain-sensitive ⁸⁶Rb⁺ influx in both. Therefore, although there appears to be a close correlation between Na⁺/K⁺ pump activation and subsequent S-phase entry following TPA stimulation, a similar correlation for PGF_2α cannot be confirmed.