Investigating toxicity specific to adjuvanted vaccines.

In an attempt to understand the unique toxicity of adjuvanted vaccines, we studied how toxicity develops over time following vaccine administration. In addition to on- and off-target toxicity typically observed with general pharmaceuticals, we observed toxicity associated with both the generation and the broad action of effectors (antibodies and/or cytotoxic T lymphocytes, CTLs). The impact on effector generation appears to be related to local tolerance specific to the adjuvant. The vaccine immune response by effectors serves to demonstrate species relevance as outlined in the recent WHO guideline on the nonclinical evaluation of adjuvanted vaccines. When regarded as pharmaceuticals that function at sites of local administration, adjuvants have inherent on- and off-target toxicity. On-target toxicity of the adjuvant is typically associated with effector generation, and could vary depending on animal species. Therefore, the use of species with sensitivity to adjuvants described in the WHO guidelines is required to evaluate the toxicity of the vaccine associated with effector generation. Changes in safety pharmacology endpoints would be considered off-target and further studies are conducted only if changes in these endpoints are observed in nonclinical or clinical studies. Thus our decision tree does not recommend the routine conduct of stand-alone safety pharmacology studies.

Remembering and forgetting: directed forgetting effect in obsessive-compulsive disorder.

It has been reported that episodic memory seems to be impaired in patients with obsessive-compulsive disorder (OCD) because the patients repeat a specific checking behavior, but it is still unknown if OCD patients show memory impairments associated with their unique symptoms or not. To study episodic memory in OCD patients, we examined the directed forgetting effect. Patients with OCD and healthy control participants were given a list of 24 emotionally neutral everyday words (12 remember [R]-cued words and 12 forget [F]-cued words) under two conditions: List and Item. The results of our study showed that OCD patients recalled a number of F-cued words similar to that for controls and relatively fewer R-cued words than controls under both List and Item conditions. Consequently, the directed forgetting effect was smaller in OCD patients than controls. Our results demonstrated that both selective encoding and retrieval inhibition processes are impaired in OCD, and we suggest that recall of unfavorable items to be forgotten intruded into necessary items to be remembered. This impairment in episodic memory may partially account for some of the unique clinical symptoms of OCD.

Factors of error and effort in memory intervention for patients with Alzheimer's disease and amnesic syndrome.

BACKGROUND: Factors of error and effort in study conditions play a crucial role in the intervention for memory-impaired individuals. In the present study, efficacy of four study conditions was compared in order to elucidate the optimal study conditions: errorless/errorful and effortless/effortful. METHODS: A total of 18 patients with Alzheimer's disease and 12 patients with amnesic syndrome received study-test sessions under four different study conditions: errorless/errorful and effortless/effortful. RESULTS: The errorless learning advantage was confirmed for both Alzheimer's disease and amnesic syndrome on both free recall and cued recall tests. In contrast, effortful learning was effective only for amnesic syndrome on a free recall test. CONCLUSION: Despite the overall advantage of errorless learning, the effortful process was effective in circumscribed situations.

Further evidence for a comparable memory advantage of self-performed tasks in Korsakoff's syndrome and nonamnesic control subjects.

Two experiments were carried out to examine memory in persons with amnesia using self-performed tasks. In Experiment 1, persons with Korsakoff's syndrome and nonamnesic participants with alcoholism learned action phrases not involving real objects by either self-performed tasks or verbal tasks. As indexed by free recall and recognition tests, a memory advantage favoring self-performed tasks was confirmed in both participant groups. In Experiment 2, persons with Korsakoff's syndrome, nonamnesic alcoholic participants, and young control participants learned object names under three different study conditions that differed from one another as to whether actions for each name were verbally generated and whether actions actually were performed. Verbal generation with or without performing the action facilitated recognition, whereas recall advantage was found only in the verbal generation-plus performance condition. These findings confirm a comparable memory advantage of self-performed tasks for a group with Korsakoff's syndrome and a group of nonamnesic comparison participants. Action memory therefore has potential therapeutic implications for memory rehabilitation.

Cross-script and within-script priming in alcoholic Korsakoff patients.

In two experiments, alcoholic Korsakoff patients and control subjects studied a list of Japanese nouns written in either Hiragana or Kanji script. Word-fragment completion and recognition tests were then administered in Hiragana. When the writing script was changed between study and test phases, repetition priming in word-fragment completion was significantly attenuated but was still reliable against baseline performance. This was confirmed for both Korsakoff patients and control subjects. In contrast, the script change had little effect on recognition memory, which was severely impaired in Korsakoff patients. The results suggest that repetition priming is mediated by two different implicit processes, one that is script-specific and the other that is assumed to operate at a more abstract level.