The use of an "over 1000-nm near-infrared (NIR) in vivo fluorescence bioimaging" system based on lanthanide containing inorganic nanostructures emitting in the visible and NIR range under 980-nm ...excitation is proposed. It may overcome problems of currently used biomarkers including color fading, phototoxicity and scattering. Gd sub(2)O sub(3):Er super( 3+),Yb super(3+) nanoparticles and nanorods showing upconversion and NIR emission are synthesized and their cytotoxic behavior is investigated by incubation with B-cell hybridomas and macrophages. Surface modification with PEG-b-PAAc provides the necessary chemical durability reducing the release of toxic Gd super(3+) ions. NIR fluorescence microscopy is used to investigate the suitability of the nanostructures as NIR-NIR biomarkers. The in vitro uptake of bare and modified nanostructures by macrophages is investigated by confocal laser scanning microscopy. In vivo investigations revealed nanostructures in liver, lung, kidneys and spleen a few hours after injection into mice, while most of the nanostructures have been removed from the body after 24 h.
We have previously shown that myelinating Schwann cells associated with motor, but not sensory, axons in peripheral nerves of adult mice express the L2/HNK-1 carbohydrate epitope. This carbohydrate ...structure carried by glycolipids and neural cell adhesion molecules has been suggested to specifically foster regrowth of motor as opposed to sensory axons after infliction of a lesion. To determine which molecular components may be the carriers of the L2 carbohydrate in motor axon-associated myelinating Schwann cells, we have isolated the purely sensory, cutaneous branch and the mixed sensory and motor muscle branch of the femoral nerve of adult mice, isolated the myelin fraction thereof and analysed the molecules expressing the L2 carbohydrate by several immunochemical methods. L2 immunoreactivity in myelin of the muscle branch was four to five times higher than that of the cutaneous branch. The 110 kDa L2-immunoreactive glycoprotein in myelin of the muscle branch, which is not L2-immunoreactive in the cutaneous branch, was identified as the myelin-associated glycoprotein by a combination of immunoprecipitation and Western blot analysis. Myelin extraction with organic solvents additionally revealed the two L2-carrying glycolipids, which amounted to approximately 40 ng glycolipid/mg dry weight in myelin of the muscle branch, whereas no significant amounts of the L2 glycolipids were found in myelin of the cutaneous branch. These observations suggest an astonishing degree of differential regulation of carbohydratesynthesizing activities in myelinating Schwann cells.
Weak inhibition within visual cortex early in life prevents experience-dependent plasticity. Loss of responsiveness to an eye deprived of vision can be initiated prematurely by enhancing ...gamma-aminobutyric acid (GABA)-mediated transmission with benzodiazepines. Here, we use a mouse "knockin" mutation to alpha subunits that renders individual GABA type A (GABAsub A) receptors insensitive to diazepam to show that a particular inhibitory network controls expression of the critical period. Only alpha1-containing circuits were found to drive cortical plasticity, whereas alpha2-enriched connections separately regulated neuronal firing. This dissociation carries implications for models of brain development and the safe design of benzodiazepines for use in infants. PUBLICATION ABSTRACT
Amino acids in the α- and γ-subunits contribute to the benzodiazepine binding site of GABA
A-receptors. We show that the mutation of a conserved histidine residue in the N-terminal extracellular ...segment (α1
H101R, α2
H101R, α3
H126R, and α5
H105R) results not only in diazepam-insensitivity of the respective αxβ2,3γ2-receptors but also in an increased potentiation of the GABA-induced currents by the partial agonist bretazenil. Furthermore, Ro 15-4513, an inverse agonist at wild-type receptors, acts as an agonist at all mutant receptors. This conserved molecular switch can be exploited to identify the pharmacological significance of specific GABA
A-receptor subtypes in vivo.
Weak inhibition within visual cortex early in life prevents experience-dependent plasticity. Loss of responsiveness to an eye deprived of vision can be initiated prematurely by enhancing ...gamma-aminobutyric acid (GABA)-mediated transmission with benzodiazepines. Here, we use a mouse "knockin" mutation to alpha subunits that renders individual GABA type A (GABA.sub.A) receptors insensitive to diazepam to show that a particular inhibitory network controls expression of the critical period. Only alpha1-containing circuits were found to drive cortical plasticity, whereas alpha2-enriched connections separately regulated neuronal firing. This dissociation carries implications for models of brain development and the sale design of benzodiazepines for use in infants.
Summary
A monoclonal antibody of IgG
2a
-type was obtained against a specific fast acting plasminogen activator inhibitor found in placenta. The placental inhibitor was purified by affinity ...chromatography using the monoclonal antibody and additionally in a FPLC-system. A strong complex formation was found between the inhibitor and urokinase and also with the two-chain form of plasminogen activator of the tissue-type. A weaker complex was found between the placental inhibitor and the one- chain form of the tissue-type activator.
Gel chromatography of proteins in urine from continent cecal urinary reservoirs revealed an abundance of high molecular weight proteins, especially secretory immunoglobulin A. Quantitation of ...immunoglobulins in urine from ileal and colonic conduits and ileal and cecal reservoirs showed secretory immunoglobulins A, G and M in amounts considerably greater than in urine from normal urinary tracts, whether or not bacteriuria was present. More secretory immunoglobulin A was found in reservoir than in conduit urine, but there was no such difference for immunoglobulin G and immunoglobulin M. In hemagglutination-inhibition tests, immunoglobulin A antibodies from cecal reservoir urine in 1 patient inhibited adherence (mannose-resistant) to human and animal erythrocytes of Escherichia coli obtained from reservoir urine from that same patient. High levels of secretory immunoglobulin A may constitute a host defense mechanism against urinary tract infection in patients with reservoirs and conduits.
Benzodiazepine tranquilizers are used in the treatment of anxiety disorders. To identify the molecular and neuronal target mediating the anxiolytic action of benzodiazepines, we generated and ...analyzed two mouse lines in which the α2 or α3 GABAA (γ-aminobutyric acid type A) receptors, respectively, were rendered insensitive to diazepam by a knock-in point mutation. The anxiolytic action of diazepam was absent in mice with the α2(H101R) point mutation but present in mice with the α3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by α2 GABAA receptors, which are largely expressed in the limbic system, but not by α3 GABAA receptors, which predominate in the reticular activating system.
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