Astrocyte and microglial motility in vitro is functionally dependent on the hyaluronan receptor RHAMM

RHAMM (Receptor for Hyaluronic Acid Mediated Motility) has been identified as a receptor for the extracellular matrix component hyaluronan (HA) and was recently shown to be essential for the locomotion of normal and transformed peripheral cells. Until now the potential role of RHAMM in the motility of neural-derived cells has not been investigated. Here, we report that cultured primary astrocytes, astrocyte cell lines, and microglia express this receptor and exhibit RHAMM-dependent motility. Immunocytochemical localization of RHAMM showed that it was often present as aggregates at the periphery of cells in contact with one another or concentrated on protruding processes of isolated cells. Glial cells contained 50 and 72 kDa forms of RHAMM, and both of these forms were found to have HA binding capacity. Time lapse imaging of cell locomotion revealed a significant inhibition of motility and process elongation by neutralizing anti-RHAMM antibodies and by peptides corresponding to the HA binding domains of RHAMM. These results demonstrate that RHAMM serves a role in glial cell locomotion in vitro and provide the basis for investigations of the motile behavior of glial cells in vivo after CNS injury.     

Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells.

Glioblastoma multiforme (GBM) is the most common subtype of primary malignant brain tumor. Although serotype 5 adenoviral vectors (Ads) have been used successfully in clinical trials for GBM, the capacity of Ads to infect human glioma cells and the expression of adenoviral receptors in GBM cells have been challenged. In this report, we studied the expression of three molecules that have been shown to mediate adenoviral entry into cells, i.e., coxsackie and adenovirus receptor (CAR), integrin alphavbeta3 (INT), and major histocompatibility complex class I (MHCI), in rodent glioma cell lines and low-passage primary cultures and cell lines from human GBM. We correlated levels of expression of CAR, INT, and MHCI with transduction efficiency elicited by several high-capacity helper-dependent adenoviral vectors (HC-Ads). Expression levels of adenoviral receptors were variable among the different GBM cells studied. HC-Ad-mediated therapeutic gene expression was efficient, ranging between 20 and 80% of the total target cells expressing the encoded transgenes. Our results show no correlation between the levels of CAR, INT, or MHCI molecules and the levels of transgene expression or the number of GBM cells transduced. We conclude that expression levels of adenoviral receptors do not predict their transduction efficiency or biological function.     

Soluble polystyrene derivatives of metal bis(3,4-dicarboxybenzoyl)phthalocyaninates: Synthesis,thermal analysis,and sensitivity towards toxic gases

Polystyrene-bound metal [2,9 or 2,10 (or 2,16 or 2,17) bis(3,4-dicarboxybenzoyl)]phthalocyaninates were synthesized by Friedel-Crafts reaction of polystyrene with the corresponding metal phthalocyaninates. Co(II) and Cu(II) [2,9 or 2,10 (or 2,16 or 2,17) bis(3,4-dicarboxybenzoyl)]-phthalocyaninate (PS-CodaPc and PS-CudaPc) contained 0,13 mmol · g^?1 (12,4 wt.-%) and 0,13 mmol · g^?1 (12,8 wt.-%) of CodaPc and CudaPc, respectively. They were soluble in N,N'-dimethylformamide, but only partially soluble in chloroform, tetrahydrofuran (THF), dimethyl sulfoxide, N-methyl-2-pyrrolidone, and pyridine. The THF extracts contained 0,12 mmol · g^?1 (11,4 wt.-%) and 0,18 mmol ? g^?1 (17,2 wt.-%) of PS-CodaPc and PS-CudaPc, respectively. The thermal stability of the polymers was studied using thermogravimetric and differential thermal analysis in nitrogen and synthetic air atmosphere. The contents of MdaPc(M: metal) in THF-extracted polymers calculated from the data of residue in thermogravimetric analysis are 0,12 mmol · g^?1 for PS-CodaPc and 0,19 mmol · g^?1 for PS-CudaPc. In addition, the sensitive properties of the polymers towards toxic gases were also investigated by quartz microbalance transducers. The results show that the quartz microbalance sensors coated with both polymers were sensitive to NO₂ and chlorinated hydrocarbons, i.e. chloroform and perchloroethylene. The sensitivity to NO₂ was 6,53 · 10^?7 m³ · mL^?1 · s^?1 for PS-CodaPc and 1,90 · 10^?6 m³ · mL^?1 · s^?1 for PS-CudaPc, and that to chloroform and perchloroethylene was 2,33 · 10^?8 and 4,60 · 10^?8 m³ · mL^?1 · s^?1, respectively, for PS-CodaPc and 4,79 · 10^?8 and 9,51 · 10^?7 m³ · mL^?1 · s^?1 for PS-CudaPc.     

Pharmacokinetics of two alternative dosage forms for cyclosporine: liposomes and intralipid

Cyclosporine (CsA), commercially available as iv or oral Sandimmune, is a potent immunosuppressant which can induce dose-related nephrotoxocity. In addition, the iv product contains a solubilizing agent, Cremophore EL, which in itself is reported to be nephrotoxic and can induce, in sensitized patients, anaphylactic reactions. Solubilization of CsA with liposomes or lipid emulsions could provide a suitable alternative dosage form for iv administration. With this in mind, male New Zealand white rabbits were given iv CsA (10 mg/kg) in three different dosage forms: (1) CsA:liposomes; (2) CsA:Intralipid (soybean oil and phospholipids); and (3) the commercially available Sandimmune (cyclosporine). The CsA concentration in whole blood samples was analyzed by HPLC. The terminal disposition half-life of CsA (t1/2 beta) ranged from 400 to 475 min and was not statistically different among the three groups. However, the distribution characteristics of CsA changed dramatically depending on the dosage form. The volume of distribution of CsA at steady state (Vdss) in Sandimmune was 2.7 +/- 0.2 L/kg and was significantly lower than that of either Intralipid (10.6 +/- 2.7 L/kg) or liposomes (7.4 +/- 2.3 L/kg). A significantly lower total body clearance (TBC) of CsA also was seen for Sandimmune (12.7 +/- 0.3 mL/min/kg) as compared with that of either Intralipid (24.4 +/- 8.2 mL/min/kg) or liposomes (18.9 +/- 3.9 mL/min/kg). Since CsA is extensively bound to lipoproteins, it is surprising that both test vehicles showed a different distribution pattern.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ein Beitrag zur periarteriellen Kalk-Eiseninkrustation der Milz

Ohne ZusammenfassungMit 2 Textabbildungen.     

Observations on electric shock treatment

Psychiatric Quarterly -