Two mechanisms for the recapture of extracellular GM2 activator protein: evidence for a major secretory form of the protein

The GM2 activator protein is a small monomeric protein containing a single site for Asn-linked glycosylation. Its only proven in vivo function is to act as a substrate specific cofactor for the hydrolysis of GM2 ganglioside by lysosomal beta-hexosaminidase A. However, we and others have shown it can act as a general glycolipid transporter at neutral pH in vitro. Any other possible in vivo functions would require that some of the newly synthesized activator molecules not be targeted to the lysosome. The lysosomal targeting mechanism for the activator has not been conclusively identified. While earlier reports suggested that it is likely through the mannose-6-phosphate receptor, another more recent report demonstrated that deficient human cells could recapture nonglycosylated, bacterially produced activator, suggesting its use of an alternate targeting pathway. Here, we demonstrate that the mannose-6-phosphate pathway is likely the major intracellular, biosynthetic route to the lysosome, as well as a high affinity recapture pathway for the endocytosis of activator protein from extracellular fluids. Additionally, we show that there exists a second lower affinity recapture pathway that requires its native protein structure, is carbohydrate independent, and likely does not involve its ability to bind glycosphingolipids in the plasma membrane. Finally, we document that the pool of newly synthesized precursor activator protein contains a majority of molecules with a complex-type oligosaccharide, which cannot contain a functional mannose-6-phosphate targeting signal. These molecules makeup the secreted forms of the protein in normal human fibroblasts.     

Independent modulation of horse airway smooth muscle by epithelium and prostanoids

The effects of epithelial removal and cyclooxygenase inhibition on contractions induced by exogenous acetylcholine (ACh) and electrical field stimulation (EFS) were evaluated in horse tracheal strips and bronchial rings. Epithelial removal potentiated the response to ACh but had no influence on the response to EFS. The effect of epithelial removal was not altered by pretreating the tissues with meclofenamate, a cyclooxygenase inhibitor. In trachealis strips, meclofenamate augmented contractions induced by EFS but not by ACh. In bronchial rings, meclofenamate augmented EFS-induced contraction to a greater extent than ACh-induced contraction. These effects of meclofenamate were epithelium-independent. We conclude that horse airway epithelium produces a relaxant factor that is not a prostanoid. Endogenous prostanoids originating from non-epithelial sites inhibit only cholinergic nerves in the trachea but both parasympathetic nerves and smooth muscle in the bronchi.     

The viscosity of liquid water at pressures up to 32 MPa

The paper reports new, preliminary measurements of the viscosity of liquid water along two isotherms as a function of pressure up to 32 MPa. The measurements have been performed with a vibrating-wire viscometer especially modified for the purpose. The instrument has been calibrated with respect to the viscosity of water at a pressure of 0.1 MPa and a temperature of 293.15 K, for which an accurate reference value is available. With due regard to the precision of the determination of individual quantities and the accuracy of the calibration data, it is estimated that the accuracy of the present results is one of ±0.3% under all conditions.Paper dedicated to Professor Joseph Kestin.     

The effects of retinol on in vitro immunoglobulin synthesis by cord blood and adult peripheral blood mononuclear cells

In this study we examined the effects of retinol (ROH), a metabolic precursor of retinoic acid (RA), on Staphylococcus aureus Cowan I (SAC)-induced immunoglobulin synthesis of cord blood mononuclear cells (CBMC) and adult peripheral blood mononuclear cells (PBMC). ROH augmented SAC-induced IgM synthesis of CBMC by 5.9 +/- 1.5-fold (n = 7, mean +/- s.d.), and IgG synthesis of adult PBMC by 16.3 +/- 5.1-fold (n = 3) at optimal concentrations of 10(-6) M and 10(-11) M, respectively. No augmenting effects could be demonstrated for the other immunoglobulin isotypes. Time-course studies showed that the synthesis of IgM by CBMC was accelerated with detectable immunoglobulin in supernatant fluids starting on day 3. ROH augmented immunoglobulin synthesis of CBMC stimulated by Epstein-Barr virus (EBV), a T cell-independent polyclonal activator, and of EBV-transformed B cell clones (2.5 +/- 0.2 and 4.1 +/- 1.5-fold increase, respectively), which suggests that ROH can act directly on B cells to enhance immunoglobulin synthesis. In contrast, when ROH was preincubated with cord blood T cells, washed and added to the B cell-enriched fraction with SAC, no increase (0.9-1.8-fold) in IgM synthesis was obtained. Thus, the principal mechanism(s) by which ROH augments immunoglobulin synthesis is by acting on B cells. This is in contrast to the immunoglobulin-enhancing effects of RA which is mediated by T cells, or T cell products, e.g. cytokine. Our studies suggest that RA and ROH may have different pathways of immunoglobulin-enhancing effects, perhaps mediated by different retinoid binding proteins resulting in gene activation and immunoglobulin synthesis.     

含淀粉聚乙烯膜的时控光降解研究

使用复合光降解剂，得到了可光降解的生物降解膜。对膜的光降解进行了考察，并对影响光降解的因素进行了讨论，结果表明，我们所制得的膜是一种较好的时控光降解膜。     

Hierarchical intelligent control with flexible AC transmission systems application

A novel hierarchical intelligent controller configuration is proposed using an artificial neural network as a control-mode classifier in the supervisory level and a set of pre-designed controllers in the lower level. Controller outputs are modified nonlinearly by the classifying signals in a structure resembling one artificial neuron with adaptively changed weights. The lower-level local controllers are implemented using neural networks. An illustrative example of this approach is based on the transient stabilization of a single-machine infinite-bus system studied in Flexible AC Transmission Systems (FACTS) research.     

Our gynecologic heritage. Robert von Olshausen (1835-1915), pioneer in surgical gynecology. 5th contribution on the history of the Berlin Society of Obstetrics and Gynecology

Robert von Olshausen was an outstanding German gynecologist at the turn of the century and a pioneer of operative gynaecology. His fields of excellency were ovarotomy, the problems of asepsis, carcinoma therapy and the development of obstetrics in general. Under his chairmansship, the Berlin Department of Obstetrics and Gynecology (Universit?ts-Frauenklinik) became the leading Clinic in Germany. For many years Olshausen was the chairman of the Berlin Society of Obstetrics and Gynecology, since 1894 as honorary chairman. The present paper is a biography of Robert von Olshausen, showing his importance for the development of the modern gynaecology in Berlin and Germany.