Determination of turnover of androstenedione to estrone via aromatase in estrogen receptor positive and negative human breast cancer cell lines [Poster 48]

In one estrogen receptor (ER) negative (MDA-MB-231) and two ER positive human breast cancer cell lines (T-47-D,SK-BR-3) we measured aromatase activity by [³H]water assay and estrone (E1) production by thin-layer chromatography. Compared with ether extraction and charcoal method, lyophilization proved to be the most sensitive technique to measure the quantity of [³H]water. The extremely low contamination of the water soluble phase by [1ß-³H]androstenedione (0.02%), as well as the lack of errors due to conjugated steroids, offers the possibility to measure changes of cellular aromatase activity even at very low levels. In contrast to SK-BR-3 and MDA-MB-231 cells, we found no aromatase activity in T-47-D cells. There was no coincidence between ER status and aromatase activity. Proliferation of tumor cells was parallel with a continuous increase of aromatase activity and E1 production during mitogenic growth phase reaching highest levels at the transition from log to plateau-phase.     

Stressful life events preceding the acute onset of schizophrenia: A cross-national study from the World Health Organization

This study reports on the findings from a WHO sponsored cross-national investigation of life events and schizophrenia. Data are presented from a series of 386 acutely ill schizophrenic patients selected from nine field research centers located in developing and developed countries (Aarhus, Denmark; Agra, India; Cali, Colombia; Chandigarh, India; Honolulu, USA; Ibadan, Nigeria; Nagasaki, Japan; Prague, Czechoslovakia; Rochester, USA). On a methodological level, the study demonstrates that life event methodologies originating in the developed countries can be adapted for international studies and may be used to collect reasonably reliable and comparable cross-cultural data on psychosocial factors affecting the course of schizophrenic disorders. Substantive findings replicate the results of prior studies which conclude that socioenvironmental stressors may precipitate schizophrenic attacks and such events tend to cluster in the two to three week period immediately preceding illness onset.The paper was prepared by these authors on behalf of the collaborating investigators listed on page 196.     

Modification of the polar head group of platelet-activating factor: influence on the biological activity

Racemic analogues of platelet-activating factor and its lyso derivatives have been prepared in which one methyl of the trimethylammonium group has been replaced by ethyl, propyl, allyl, or carboxymethylene. The influence of chemical modification on the biological activity was assessed by measuring platelet aggregation and desensitization. The results point to a crucial role of a positively charged polar head group for the expression of biological activity of platelet-activating factor. There are also some indications of a more non-specific interaction of the polar head group of platelet-activating factor with its platelet binding sites.     

Human platelet electrorotation change induced by activation: inducer specificity and correlation to serotonin release

Electrorotation of single platelets was compared with [14C]serotonin release, aggregation and electron microscopy. Activation of washed and degranulated platelets was induced by thrombin, arachidonic acid, collagen, adrenaline, platelet activation factor (PAF), ADP and A23187. A strong correlation between electrorotation decrease and serotonin release was found. Electrorotation did not correlate with aggregation. It was concluded that an increase of the specific conductivity of the platelet membrane by three orders of magnitude (approx. 1.0.10(-7) S.m-1 to 1.0.10(-4) S.m-1) upon activation was responsible for the observed decrease of anti-field rotation and the shift of the first characteristic frequency towards higher values. Electrorotation allowed for time-dependent measurements of activation. Characteristic activation times in the order of minutes were found. There was the following sequence of activators classified by increasing activation time constants: A23187 was the fastest followed by thrombin, collagen, PAF, arachidonic acid, adrenaline, and ADP.     

Multi-Type Galton-Watson Process As A Model For Proliferating Human Tumour Cell Populations Derived From Stem Cells: Estimation of Stem Cell Self-Renewal Probabilities In Human Ovarian Carcinomas

Abstract. A mathematical model for proliferation of tumour cell populations is developed. the cell population is assumed to be organized in a hierarchy of decreasing proliferative potential and increasing degree of differentiation. Using some elements of the theory of Multi-type Galton-Watson processes, a method is proposed for the estimation of P_sr, the probability of self-renewal of tumour stem cells, from the experimental distribution of clonal unit sizes obtained in cell culture studies. Six data sets from patients with advanced adenocarcinorna of the ovary are used to demonstrate the method. Reasonable estimates are obtained, and the theoretical colony size distributions predicted by the model appear to be in good qualitative agreement with the experimental ones, and lend support to a stem cell model of tumour growth. the possible significance of P_sr as a prognostic factor is briefly discussed.     

Physical separation of hemopoietic stem cells from cells forming colonies in culture

Mouse bone marrow cells in suspension were separated into a number of fractions on the basis of cell density by equilibrium density gradient centrifugation, or on the basis of cell size by velocity sedimentation. After each type of separation, the cells from the various fractions were assayed for their ability to form macroscopic spleen colonies in irradiated recipient mice, and for their ability to form colonies in a cell culture system. The results from either separation technique demonstrate that cells in some fractions formed more colonies in vivo than in the culture system, while cells in other fractions formed more colonies in culture than in the spleen. The results of control experiments indicate that this separation of the two types of colony-forming cells was not an artifact of the separation procedures. From these experiments it was concluded that the population of cells which form colonies in culture under the conditions used is not identical to the population of cells detected by the spleen colony assay.     

Dose-dependent effects of DDAVP on memory in healthy young adult males: a preliminary study

Although several studies have demonstrated the efficacy of the vasopressin analog DDAVP in enhancing human memory, no previous study has reported the dose-response relationship of DDAVP to memory in healthy young adults. The present study was undertaken to explore the dose-response curve for DDAVP on recall of implicational sentences. Five doses of DDAVP (0, 5, 15, 30, and 60 micrograms) were administered intranasally to healthy young adult male volunteers. Results demonstrated a facilitation in cued recall after treatment with the 60-micrograms dose and a general impairment in recall after treatment with the 15-micrograms dose. These effects were independent of subject's weight, vocabulary ability, and concentration of salivary cortisol.     

The complex circadian system of Gonyaulax polyedra

Circadian oscillations are a fundamental biological property from bacteria to humans. The molecular mechanisms which produce a ca 24-h rhythmicity are still unknown but it has become clear that they are part of the biochemical machinery of the single cell. The cellular circadian system can be favorably studied in single-cell organisms such as the dinoflagellate Gonyaulax polyedra . The complexity of this circadian model system, which consists of at least two circadian oscillators, receives light via two input systems with different spectral sensitivities, and has several feed–back loops between the central oscillator(s) and the environment, is described here.     

Vertically stratified frugivore community composition and interaction frequency in a liana fruiting across forest strata

Vertical stratification is a key feature of tropical forests and structures plant–frugivore interactions. However, it is unclear whether vertical differences in plant-frugivore interactions are due to differences among strata in plant community composition or inherent preferences of frugivores for specific strata. To test this, we observed fruit removal of a diverse frugivore community on the liana Marcgravia longifolia in a Peruvian rain forest. Unlike most other plants, Marcgravia longifolia produces fruits across forest strata. This enabled us to study effects of vertical stratification on fruit removal without confounding effects of plant species and stratum. We found a high number of visits of a few frugivore species in the understorey and a low number of visits of many different frugivores in the canopy and midstorey. Whereas partial and opportunistic frugivores foraged across strata with differing frequencies, obligate frugivores were only found eating fruits in the higher strata. Avian frugivores foraging in the canopy were mainly large species with pointed wings, whereas under- and midstorey avian foragers were smaller with rounded wings. Our findings suggest a continuous shift in the frugivore community composition along the vertical gradient, from a few generalized frugivores in the understorey to a diverse set of specialized frugivores in the canopy. This shift in the frugivore community leads to correlated, reciprocal changes from specialized to generalized plant-frugivore interactions. Thus, we conclude that vertical niche differentiation between species in tropical forests persists even when food resources are available across strata. This highlights its role for promoting biodiversity and ecosystem functioning.     

Oxide-Based Solid-State Batteries: A Perspective on Composite Cathode Architecture

The garnet-type phase Li₇La₃Zr₂O₁₂ (LLZO) attracts significant attention as an oxide solid electrolyte to enable safe and robust solid-state batteries (SSBs) with potentially high energy density. However, while significant progress has been made in demonstrating compatibility with Li metal, integrating LLZO into composite cathodes remains a challenge. The current perspective focuses on the critical issues that need to be addressed to achieve the ultimate goal of an all-solid-state LLZO-based battery that delivers safety, durability, and pack-level performance characteristics that are unobtainable with state-of-the-art Li-ion batteries. This perspective complements existing reviews of solid/solid interfaces with more emphasis on understanding numerous homo- and heteroionic interfaces in a pure oxide-based SSB and the various phenomena that accompany the evolution of the chemical, electrochemical, structural, morphological, and mechanical properties of those interfaces during processing and operation. Finally, the insights gained from a comprehensive literature survey of LLZO–cathode interfaces are used to guide efforts for the development of LLZO-based SSBs.