Mechanism of action of levonorgestrel: in vitro metabolism and specific interactions with steroid receptors in target organs.

Levonorgestrel (LNG) is a synthetic steroid that displays potent progestional and androgenic effects but it lacks estrogen-like activity. To examine the mode of action of this progestin, we studied its metabolism in vitro in target organs and the specific interactions of LNG and its metabolites with putative steroid receptors. The results demonstrated that [³H]LNG was efficiently converted to A-ring reduced derivatives when incubated with rat hypothalamus and pituitary. Under optimal incubation conditions, [³H]5-dihydro LNG (5-LNG) and [³H]3-5-tetrahydro LNG (3,5-LNG) were identified as the major metabolic conversion products, while [³H]3ß, 5-LNG formation occured to a lesser extent. A-ring reduction of LNG was NADPH-dependent. Assessment of the relative binding affinities of LNG and its derivatives to progesterone (PR), androgen (AR) and estrogen (ER) receptors by displacement analysis revealed that unchanged LNG binds with high affinity to PR and AR but not to ER. 5-LNG exhibited a diminished though significant interactions with PR and an enhanced binding affinity for AR as compared with LNG, indicating that 5-reduction of LNG increases its affinity for AR. The most striking finding was that further reduction of the 5-LNG molecule at C-3 abolished its binding activity to PR, AR, and even to ER. The overall data provides a plausible explanation for the lack of estrogen agonistic action of LNG and for its potent progestational and androgenic effects.     

Wide distribution of a 36-megadalton plasmid among clinical and environmental Spanish isolates ofLegionella pneumophila serogroup 1

With the eventual goal of characterizingLegionella pneumophila serogroup 1 plasmids at the molecular level, we have analyzed the plasmid contents of 78 clinical and environmental Spanish isolates. After selection of a suitable alkaline lysis method, we detected plasmids with approximate molecular weights of 25, 36, 40, 61, 80, 85, 90, and 95 megadalton (MDal). Several factors (i.e., wide temporal and geographic distribution, high frequency in both clinical and environmental isolates, and apparent high copy number after subculturing) make the 36 MDal type IA plasmid an appropriate plasmid for further molecular studies.     

A critical scanning electron microscope study of the scolex of Bothriocephalus acheilognathi Yamaguti, 1934, with a review of the taxonomic history of the genus Bothriocephalus parasitizing cyprinid fishes

Summary Bothriocephalus specimens from one Ctenopharyngodon idella (O+) were fixed using three different techniques and the scolex morphology was examined using scanning electron microscopy. The scolices were compared with figures of the five species of Bothriocephalus and one species of Schyzocotyle previously described from cyprinid fishes. The taxonomic history of the Bothriocephalus species parasitizing cyprinid fish is reviewed. It is concluded that there is only one Bothriocephalus species parasitizing cyprinid fishes, and that continued use should be made of the name B. acheilognathi Yamaguti, 1934. ac]19840326     

The effect of praziquantel on the pseudophyllidean cestode Bothriocephalus acheilognathi in vitro

Adult Bothriocephalus acheilognathi were incubated in solutions containing 0 (control), 0.1, 1.0, 10.0 and 100 micrograms praziquantel per ml (0, 10(2), 10(3), 10(4) and 10(5) micrograms l-1) of 0.9% saline for 5, 15 and 60 min at a temperature of 18 degrees C. The worms contracted immediately upon being placed in the drug. Scanning and transmission electron microscopy revealed considerable tegumental damage particularly in the neck region. Vacuolization and 'bubbling' of the tegument occurred in all of the drug solutions tested. Exposure to drug concentrations of more than 1.0 micrograms ml-1 (10(3) micrograms l-1) praziquantel for 15 min or greater resulted in many of the 'bubbles' bursting and releasing their contents to the exterior. Mature proglottides were distorted and had occasional large swellings resulting in the mass expulsion of eggs. Praziquantel had no ovicidal activity. Exposure to drug concentrations of 100 micrograms (10(5) micrograms l-1) praziquantel per ml saline for 24 h was not lethal to the worms.     

Differential recognition of the serologically defined HLA-A2 antigen by allogeneic cytotoxic T cells

A comprehensive analysis of human alloimmune cytotoxic T lymphocytes (CTLs) specific for the HLA-A2 antigen identified 11% of HLA-A2 positive cells as outliers. In total, 11 unrelated serologically indistinguishable, but distinguishable by cell-mediated lympholysis (CML) HLA-A2 positive outlier cells were identified. The outlier cells could be subdivided in two subgroups according to reactivity patterns obtained with CTLs directed against the HLA-A2 antigen of outlier cells and their inhibitory capacity in specific competitive inhibition experiments. Thus, the serologically defined HLA-A2 specificity can be divided into at least three subtypes using CTLs specific for the HLA-A2 antigen. Moreover, CTLs specific for an HLA-A2 subtype could be induced when responder cells expressed a different HLA-A2 subtype antigen. On the basis of several family studies, we conclude that the subtype HLA-A2 antigens are inherited in a codominant way.     

Mapping in the mouse of the region homologous to the rat growth and reproduction complex (grc)

Offprint requests: J. Klein.     

Evaluation of rice straw hemicellulose hydrolysate in the production of xylitol byCandida guilliermondii

Summary Rice straw was used as a lignocellulosic source to provide rich pentose media. By using a well characterized yeast strain,Candida guilliermondii FTI 20037, the hydrolysate obtained was converted to xylitol with an efficiency of 75% and production of 27 g of xylitol per liter in 48 hours. The satisfactory results reported here can be attributed to the low concentrations of toxic components generated throughout the chemical depolymerization of this raw material.     

Soils in warmer and less developed countries have less micronutrients globally

Soil micronutrients are capital for the delivery of ecosystem functioning and food provision worldwide. Yet, despite their importance, the global biogeography and ecological drivers of soil micronutrients remain virtually unknown, limiting our capacity to anticipate abrupt unexpected changes in soil micronutrients in the face of climate change. Here, we analyzed >1300 topsoil samples to examine the global distribution of six metallic micronutrients (Cu, Fe, Mn, Zn, Co and Ni) across all continents, climates and vegetation types. We found that warmer arid and tropical ecosystems, present in the least developed countries, sustain the lowest contents of multiple soil micronutrients. We further provide evidence that temperature increases may potentially result in abrupt and simultaneous reductions in the content of multiple soil micronutrients when a temperature threshold of 12–14°C is crossed, which may be occurring on 3% of the planet over the next century. Altogether, our findings provide fundamental understanding of the global distribution of soil micronutrients, with direct implications for the maintenance of ecosystem functioning, rangeland management and food production in the warmest and poorest regions of the planet.