Fate of antibodies bound to lymphocyte surface. II.--Degradation and release of immune complexes

The fate of horse anti-human lymphocyte globulins, rabbit anti-human beta2 microglobulin antibodies and anti-HL-A alloantibodies radiolabelled with 125I and complexed to their corresponding lymphocyte surface antigens, was investigated. During prolonged incubation at 37 degrees C, part of these antibodies were actively released into the surrounding medium after enzymatic degradation occuring either intracellularly or at the cell surface. Metabolism of the antibodies was temperature-dependent and involved only antibodies able to react with antigens on the cell surface. Sephadex G200 filtration of the small percentage of non dialysable radioactive products in the supernatant revealed that all the 125I-anti-human lymphocyte globulin was recovered as a macromolecular structure in the void volume. Similar experiments were performed with 51Cr labelled lymphocytes coated with anti-lymphocyte globulins: treatment with anti-horse immunoglobulin precipitated part of 51Cr activity in the void volume which was therefore associated with anti-human lymphocyte globulin as an immune complex. The same protocol applied to the other two antibodies studied showed that anti-beta2 microglobulin antibodies were recovered both as macromolecular and 7 S immune complexes, whereas anti-HL-A antibodies were recovered as macromolecular, 7 S and still smaller immune complexes.     

The 1.1 A resolution crystal structure of [Tyr15]EpI, a novel alpha-conotoxin from Conus episcopatus, solved by direct methods

Conotoxins are valuable probes of receptors and ion channels because of their small size and highly selective activity. alpha-Conotoxin EpI, a 16-residue peptide from the mollusk-hunting Conus episcopatus, has the amino acid sequence GCCSDPRCNMNNPDY(SO3H)C-NH2 and appears to be an extremely potent and selective inhibitor of the alpha3beta2 and alpha3beta4 neuronal subtypes of the nicotinic acetylcholine receptor (nAChR). The desulfated form of EpI ([Tyr15]EpI) has a potency and selectivity for the nAChR receptor similar to those of EpI. Here we describe the crystal structure of [Tyr15]EpI solved at a resolution of 1.1 A using SnB. The asymmetric unit has a total of 284 non-hydrogen atoms, making this one of the largest structures solved de novo by direct methods. The [Tyr15]EpI structure brings to six the number of alpha-conotoxin structures that have been determined to date. Four of these, [Tyr15]EpI, PnIA, PnIB, and MII, have an alpha4/7 cysteine framework and are selective for the neuronal subtype of the nAChR. The structure of [Tyr15]EpI has the same backbone fold as the other alpha4/7-conotoxin structures, supporting the notion that this conotoxin cysteine framework and spacing give rise to a conserved fold. The surface charge distribution of [Tyr15]EpI is similar to that of PnIA and PnIB but is likely to be different from that of MII, suggesting that [Tyr15]EpI and MII may have different binding modes for the same receptor subtype.     

Investigations of some aspects of atmospheric pollution by anaesthetic gases. II: Aspects of adsorption and emission of halothane by different charcoals

Four different charcoals have been assessed by exposure to halothane in air until 10, 100 and 500 p.p.m. (v/v) effluent was detectable. The pattern of halothane adsorption, its practical implications and the behaviour of different adsorbers has been demonstrated. The effluent concentration from a charcoal canister should be not more than 10 p.p.m. during the adsorption of 1.5% halothane from a gas flow of 5 litre/min. When 100 p.p.m. is detectable the charcoal should be considered exhausted.     

Topostatin, a novel inhibitor of Topoisomerases I and II produced by Thermomonospora alba strain No. 1520. II. Physico-chemical properties and structure elucidation

Topostatin is a new topoisomerase inhibitor isolated from the culture filtrate of Thermononospora alba strain No. 1520. The inhibitor inhibits topoisomerases I and II, and it has neither ability to stabilize the cleavable complex nor ability to intercalate into DNA strands. The molecular formula of topostatin was determined as C36H58N4O11S based on the FAB-MS analyses, and the structure was elucidated to be a novel 14-membered ring containing peptide and terpenoid by various NMR spectroscopies.     

Modelling mucoadhesion by use of surface energy terms obtained from the Lewis acid-Lewis base approach. II. Studies on anionic, cationic, and unionisable polymers

Surface energies of carbopol, chitosan, hydroxypropyl cellulose (HPC) and poly(HEMA) were assessed from contact angle and surface tension experiments. The surface energy was considered in terms of an apolar Lifshitz-van der Waals term and a polar acid-base term, which in turn is divided into electron donor and electron receptor (Lewis acid-Lewis base) contributions. Using these surface energy terms the interaction of dry and hydrated polymer with mucin in the presence of either artificial gastric or intestinal fluid, or saline was predicted. The predictions were related to measured forces of detachment. There was a significant difference between the surface energy on dry and hydrated HPC and also for carbopol; for the other polymers either the surface energy of the hydrated material was not detectable, or the effect of hydration was minimal. There were good correlations between mucoadhesive strength and the calculated free energies of interaction between mucin and polymer in the presence of each of the fluids, for each individual polymer. Thus, two trends were observed, one for unionisable and the other for ionisable polymers. It is argued that the increased mucoadhesion seen with ionisable polymers (compared with the predicted value based on results of unionisable polymers) is a direct result of the ionic interaction. No attempt has been made to correct for the ionisation effect, but the surface energy predictions provide insight into the mechanism of the mucoadhesion process. This approach is useful for understanding and predicting interactions between different materials and biological components.