Ethanol Feeding Causes Inactivation of Both State 1 and State 2 Rat Hepatic Asialoglycoprotein Receptors

Previous studies have shown that ethanol feeding in rats causes inactivation and redistribution of ˜50% of the total asialoglycoprotein receptors (ASGPRs) in hepatocytes (Tworek et al., J. Biol. Chem. 271:2531, 1996), and that two equal populations of hepatic ASGPRs mediate ligand uptake and processing via two functionally different pathways (Weigel in Glycoconjugates: Composition, Structure and Function , Marcel Dekker, 1992, p. 421). The purpose of this study was to determine if ethanol feeding causes preferential inactivation of only one of these two ASGPR populations, which have been designated state 1 and state 2 ASGPRs. The state 2, but not state 1, ASGPRs are inactivated in isolated hepatocytes by a variety of drugs and inhibitors. State 2 ASGPRs can also be inactivated in permeable cells by ATP treatment and then reactivated by treatment with fatty acyl coenzyme As. In the present study, permeable cell assays for state 2 ASGPR inactivation and reactivation were used to assess whether hepatocytes from ethanol-fed rats contain inactive state 2 ASGPRs. The results show that preferential inactivation of one ASGPR population does not occur after ethanol feeding. That inactive ASGPRs could not be reactivated by treatment with palmitoyl-coenzyme A to a greater extent in ethanol-fed versus control cells indicates there is not a larger pool of inactivated state 2 ASGPRs in treated cells. We conclude that ethanol feeding causes equal inactivation of both state 1 and state 2 ASGPRs. Ethanol feeding may represent the first treatment found to inactivate state 1 ASGPRs.     

The structure of wandering in dementia

‘Wandering’ is one of the most troublesome of behavioural problems in dementia. The term ‘wandering’ covers many different types of behaviour. We examined the hypothesis that the different types of wandering behaviour seen in dementia from a scale using data collected on 83 elderly subjects suffering from either Alzheimer's disease or multiinfarct dementia. We reject the scaling hypothesis. Our data suggest that there are three main categories of wandering behaviour, and that one of these categories is usefully divided into four subcategories.     

A Novel Variant of the Human Blood Group K1 Antigen

A discrepancy in duplicate anti-K1 typing in a parentage case led to the discovery of an unusual K1 blood group antigen. Red blood cells from the propositus (JC) express a rare variant of the K1 antigen that is detectable by only 8 of 72 sera containing anti-K1. Absorption and elution studies using reactive anti-K1 confirmed the presence of a K1 antigen. Nonreactive anti-K1 was not absorbed by or eluted from JC's red blood cells. Red cells from 3 of the propositus's siblings also had the variant K1 antigen. The variant antigen exhibited qualitative as well as quantitative differences as compared to normal K1, and we have named it K1var.     

C1: molecular interactions with activating systems.

The molecular events controlling complement activation have been gradually unravelled over the past three decades, stimulated by improved isolation procedures and a better understanding of the roles of individual proteins. In this review, Bob Sim and Ken Reid examine the interactions between C1q and its numerous ligands in the initiation of the classical pathway cascade.     

Effects of intravenous S-9780, an angiotensin-converting enzyme inhibitor, in normotensive subjects

S-9780 is the active diacid metabolite of the new angiotensin-converting enzyme (ACE) inhibitor perindopril. In a double-blind, randomised, crossover study, the effects of 1, 2, and 4 mg of S-9780 administered intravenously (i.v.) were compared with placebo in eight normotensive subjects. All active doses caused immediate, maximal, and similar inhibition of plasma ACE with 40% inhibition persisting after 48 h. Plasma renin activity was elevated 4 and 8 h after dosing, but no effect on plasma aldosterone, adrenaline or noradrenaline levels was detected. Diastolic blood pressure was lowered by 4 mg of S-9780 until 24 h after dosing. Heart rate did not change. The pharmacokinetics of S-9780 fitted a three-compartment model with a terminal half-life (t1/2) of 31 h. Inhibition of plasma ACE was closely related to observed drug concentration, with 1.8 +/- 0.9 ng/ml (mean +/- S.D.) producing 50% inhibition of the enzyme. S-9780 caused predictable effects on the cardiovascular and renin angiotensin systems.     

Immunomodulation of Delayed Hypersensitivity to Methylated Bovine Serum Albumin (MBSA) in Mice Using Subliminal and Normal Sensitization Procedures

Delayed hypersensitivity (DH) was induced in the footpads of mice sensitized to methylated bovine serum albumin (MBSA). The magnitude of this DH response increased with increasing sensitizing concentration of MBSA. Levamisole administered 1 hr prior to MBSA challenge stimulated the DH response and this was optimal using subliminal sensitizing concentrations of antigen. A number of antirheumatic agents, immunomodulators mediator antagonists and antiallergies were subsequently examined using the subliminal sensitizing concentration of MBSA. The same drugs were also evaluated using a normal sensitizing procedure. These studies indicate that the sensitizing concentration of antigen is critical in establishing whether a drug will stimulate or suppress a DH response.