Spatial and nonspatial implicit motor learning in Korsakoff’s amnesia: evidence for selective deficits

Patients with amnesia have deficits in declarative memory but intact memory for motor and perceptual skills, which suggests that explicit memory and implicit memory are distinct. However, the evidence that implicit motor learning is intact in amnesic patients is contradictory. This study investigated implicit sequence learning in amnesic patients with Korsakoff’s syndrome (N = 20) and matched controls (N = 14), using the classical Serial Reaction Time Task and a newly developed Pattern Learning Task in which the planning and execution of the responses are more spatially demanding. Results showed that implicit motor learning occurred in both groups of participants; however, on the Pattern Learning Task, the percentage of errors did not increase in the Korsakoff group in the random test phase, which is indicative of less implicit learning. Thus, our findings show that the performance of patients with Korsakoff’s syndrome is compromised on an implicit learning task with a strong spatial response component

COUPLING OF THE ANTIVIRAL DRUG ARA-AMP TO LACTOSAMINATED ALBUMIN LEADS TO SPECIFIC UPTAKE IN RAT AND HUMAN HEPATOCYTES

We covalently coupled 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) to the carrier molecule lactosaminated human serum albumin using a water-soluble carbodiimide with a two-step conjugation method (pH 4.5 and pH 7.5) instead of the commonly used single-step conjugation at pH 7.5. This resulted in a predominantly monomeric conjugate (lac27-HSA-ara-AMP9). The conjugate was stable in buffer (pH 7.4) and blood plasma. After in vivo injection, the carrier and the monomeric conjugate were subjected to selective endocytosis in rat hepatocytes, as shown on immunohistochemical study and cell-separation techniques using I-125-labeled material. In competition experiments with other ligands for the asialoglycoprotein receptor N-acetylgalactosamine and asialofetuin, we showed that both lactosaminated human serum albumin and lac27-HSA-ara-AMP, are subject to endocytosis by this receptor system. Although the coupling of ara-AMP significantly increased the net negative charge of the conjugate compared with the native carrier, liver uptake was not affected by coadministration of an excess of succinylated human serum albumin (suc-HSA), a negatively charged ligand for the scavenger receptor. Incubation studies with purified rat liver lysosomes showed that in this acidic and proteolytic environment, mainly ara-AMP and, to a much lesser extent, ara-A itself were released from the carrier. After injection into the rat in vivo and in isolated perfused rat liver, no free ara-AMP or 9-B-D-arabinofuranosyladenine (ara-A) could be detected in plasma and perfusate, respectively, indicating proper retention of the virally active components in hepatocytes. Uptake experiments with freshly isolated rat and human hepatocytes indicated that human hepatocytes can also carry out endocytosis of lactosaminated human serum albumin and the ara-AMP conjugate by means of the galactose-recognizing receptor