Migratory, invasive and metastatic capacity of NCAM transfected rat glioma cells

A cDNA encoding a transmembrane 140 kDa isoform of the neural cell adhesion molecule, NCAM, was transfected into the rat glioma cell line BT4Cn. Transfectants with a homogeneously high expression of NCAM-B showed a decreased capacity for penetration of an artificial basement membrane when compared to cells transfected with expression-vector alone or untransfected cells. However, when injected subcutaneously into nude mice, both NCAM expressing cells and control cells produced invasive tumors. Nude mice injected with NCAM positive cells developed tumors with slower growth rates as compared to those induced by NCAM negative cells. This implies that NCAM may not only be involved in adhesive and motile behaviour of glioma cells, but also in their growth regulation.     

Infratentorial Cerebral Cryptococcosis

In a nonimmunocompromised patient with cerebral cryptococcosis, unique magnetic resonance findings included abnormalities limited to the posterior fossa and cerebellar hemispheric edema, gyriform enhancement of the vermis and cerebellar hemispheres, and infratentorial plaquelike enhancement. Magnetic resonance findings in central nervous system cryptococcosis are discussed.     

Altered cAMP Response after Isoprenaline Stimulation of Mononuclear Leucocytes from Insulin-Dependent Diabetic Patients with Hypoglycaemia Unawareness

Abstract: Loss of adrenergic hypoglycaemic symptoms is the most distinctive feature in insulin-dependent diabetes mellitus (IDDM) patients with hypoglycaemia unawareness. Previous reports from in vivo studies show reduced heart rate responsiveness both to adrenergic agonists and antagonists in these patients. This study was carried out to investigate whether the reduced adrenergic sensitivity in IDDM patients with hypoglycaemia unawareness (IDDM-unaware) also could be demonstrated as reduced increase in cAMP production in mononuclear leucocytes induced by isoprenaline stimulation, or reduced inhibition by ICI-118551 (a selective β₂-adrenergic receptor blocker) of isoprenaline induced cAMP production. We found that the slope of the concentration-response curves of isoprenaline/cAMP and the maximal cAMP concentrations obtained after isoprenaline stimulation were reduced in IDDM-unaware compared to control and IDDM patients with normal hypoglycaemia awareness (IDDM-aware). We did not find any significant differences in the response to ICI-118551 between control, IDDM-aware and IDDM-unaware. This study supports the reports of reduced sensitivity of adrenergic agonists as a part of the pathophysiological changes in hypoglycaemia unawareness, but we have not been able to confirm the reports of an association between hypoglycaemia unawareness and reduced effect of adrenergic antagonists.     

Molecular structure and dynamics of serotonin.

The electronic structure and low-energy conformations of the protonated serotonin molecule were examined by quantum mechanical and molecular mechanical calculations based on the AMBER force field. The flexibility and internal motions of the molecule, which may be important for its mode of receptor interaction, were examined by molecular dynamics simulations in vacuo and in aqueous solution. Two crystal structures and four computed serotonin structures were used as starting points in the calculations. Both gauche and anti conformers were observed during molecular dynamics simulations in aqueous solution, but only gauche conformers of serotonin were observed in vacuo. The simulations demonstrated that the side chain conformation may adjust in order to fit into a receptor binding site. Energy refined gauche conformers had lowest molecular energies both in vacuo and in aqueous solution. Ab initio molecular electrostatic potentials were calculated in 4 layers surrounding the molecule and projected into net atomic point charges. The effect of the hydroxyl group in lowering the molecular electrostatic potentials around the phenyl ring was highly dependent on the conformation of the side chain. Conformers with an extended side chain had significantly lower electrostatic potentials over the phenyl ring than those with a folded conformation.