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Biomedical subjects

J M Gardiner

Publications and source records attributed to J M Gardiner.

At least 19 recordsLinked to original sources

Experiences of remembering, knowing, and guessing.

This article presents and discusses transcripts of some 270 explanations subjects provided subsequently for recognition memory decisions that had been associated with remember, know, or guess responses at the time the recognition decisions were made. Only transcripts for remember responses included reports of recollective experiences, which seemed mostly to reflect either effortful elaborative encoding or involuntary reminding at study, especially in relation to the self. Transcripts for know responses included claims of just knowing, and of feelings of familiarity. These transcripts indicated that subjects were often quite confident of the accuracy of their decisions, compared with those for guess responses. Transcripts for decisions associated with guess responses also expressed feelings of familiarity but additionally revealed various strategies and inferences that did not directly reflect memory for studied items. The article concludes with a historical and theoretical overview of some interpretations of the states of awareness measured by these responses.

Association Learning

Depth-of-processing effects on priming in stem completion: tests of the voluntary-contamination, conceptual-processing, and lexical-processing hypotheses.

Depth-of-processing effects on incidental perceptual memory tests could reflect (a) contamination by voluntary retrieval, (b) sensitivity of involuntary retrieval to prior conceptual processing, or (c) a deficit in lexical processing during graphemic study tasks that affects involuntary retrieval. The authors devised an extension of incidental test methodology--making conjunctive predictions about response times as well as response proportions--to discriminate among these alternatives. They used graphemic, phonemic, and semantic study tasks, and a word-stem completion test with incidental, intentional, and inclusion instructions. Semantic study processing was superior to phonemic study processing in the intentional and inclusion tests, but semantic and phonemic study processing produced equal priming in the incidental test, showing that priming was uncontaminated by voluntary retrieval--a conclusion reinforced by the response-time data--and that priming was insensitive to prior conceptual processing. The incidental test nevertheless showed a priming deficit following graphemic study processing, supporting the lexical-processing hypothesis. Adding a lexical decision to the 3 study tasks eliminated the priming deficit following graphemic study processing, but did not influence priming following phonemic and semantic processing. The results provide the first clear evidence that depth-of-processing effects on perceptual priming can reflect lexical processes, rather than voluntary contamination or conceptual processes.

Adult

Asperger's syndrome and memory: similarity to autism but not amnesia.

Two experiments are described in which the memory of adults with Asperger's syndrome is compared with that of verbal IQ controls. The results of the first experiment showed that the Asperger subjects resembled autistic adults and children in their failure to use category information to aid their free recall. In the second experiment, both groups of subjects showed similar priming effects in an implicit stem completion task and similar performance on an explicit cued recall task. Moreover, both groups also showed more priming for items that they had read at study and better recall for items that they had to generate at study, suggesting that the cued recall of the Asperger subjects did not result from contamination by automatic or involuntary processes.

Adult

Changes in memory awareness during learning: the acquisition of knowledge by psychology undergraduates.

First-year psychology students took multiple-choice examinations following each of 4 lecture courses and 3 laboratory research methods courses. One lecture course was later retested. Students indicated state of memory awareness accompanying each answer: recollective experience (remember), "just know" (know), feeling of familiarity (familiarity), or guess. On the lecture courses, higher performing students differed from other students because they had more remember responses. On research methods, higher performing students differed because they knew more, and in the delayed retest, higher performing students differed because they now knew rather than remembered more. These findings demonstrate a shift from remembering to knowing, dependent upon level attained, type of course, and retention interval, and suggest an underlying shift in knowledge representation from episodic to semantic memory. The authors discuss theoretical and educational implications of the findings.

Achievement

Molecular and genetic analysis of REC103, an early meiotic recombination gene in yeast.

In the yeast Saccharomyces cerevisiae at least 10 genes are required to begin meiotic recombination. A new early recombination gene REC103 is described in this paper. It was initially defined by the rec103-1 mutation found in a selection for mutations overcoming the spore inviability of a rad52 spo13 haploid strain. Mutations in REC103 also rescue rad52 in spo13 diploids. rec103 spo13 strains produce viable spores; these spores show no evidence of meiotic recombination. rec103 SPO13 diploids produce no viable spores, consistent with loss of recombination. Mutations in REC103 do not affect mitotic recombination, growth, or repair. These phenotypes are identical to those conferred by mutations in several other early meiotic recombination genes (e.g., REC102, REC104, REC114, ME14, MER2, and SPO11). REC103 maps to chromosome VII between ADE5 and RAD54. Cloning and sequencing of REC103 reveals that REC103 is identical to SK18, a gene that depresses the expression of yeast double-stranded ("killer") (ds)RNA viruses. REC103/SK18 is transcribed in mitotic cells and is induced approximately 15-fold in meiosis. REC103 has 26% amino acid identity to the Schizasaccharomyces pombe rec14+ gene; mutations in both genes confer similar meiotic phenotypes, suggesting that they may play similar roles in meiotic recombination.

Chromosome Mapping

Synthesis and iron binding studies of myo-inositol 1,2,3-trisphosphate and (+/-)-myo-inositol 1,2-bisphosphate, and iron binding studies of all myo-inositol tetrakisphosphates.

The first syntheses of the natural products myo-inositol 1,2,3-trisphosphate and (+/-)-myo-inositol 1,2-bisphosphate are described. The protected key intermediates 4,5,6-tri-O-benzoyl-myo-inositol and (+/-)-3,4,5,6-tetra-O-benzyl-myo-inositol were phosphorylated with dibenzyl N,N-di-isopropylphosphoramidite in the presence of 1H-tetrazole and subsequent oxidation of the phosphite. The crystal structures of the synthetic intermediates (+/-)-1-O-(tert-butyldiphenylsilyl)-2,3,O-cyclohexylidene-myo-inos itol and (+/-)-4,5,6-tri-O-benzoyl-1-O-(tert-butyldiphenylsilyl)-2,3-O-cycl ohexylidene- myo-inositol are reported. myo-Inositol 1,2,3-trisphosphate, (+/-)-myo-inositol 1,2-bisphosphate, and all isomeric myo-inositol tetrakisphosphates were evaluated for their ability to alter HO. production in the iron-catalysed Haber-Weiss reaction. The results demonstrated that a 1,2,3-grouping of phosphates in myo-inositol was necessary for inhibition, also that (+/-)-myo-inositol 1,2-bisphosphate potentiated HO. production. myo-Inositol 1,2,3-trisphosphate resembled myo-inositol hexakisphosphate (phytic acid) in its ability to act as a siderophore by promoting iron-uptake into Pseudomonas aeruginosa.

Binding Sites

Acyclic nucleosides as antiviral compounds.

Acyclovir is an effective drug for the treatment of HSV and VZV infections, which after phosphorylation to the triphosphate, inhibits viral DNA polymerase. Acyclovir has low oral bioavailability, therefore prodrugs have been developed, and the L-valyl ester, valaciclovir, recently has been licensed for the treatment of shingles. Ganciclovir is used against CMV, and famciclovir, a lipophilic prodrug of penciclovir, is marketed for shingles. The acyclic nucleoside phosphonates are active against thymidine kinase-resistant viral strains. Promising analogs are PMEA (in clinical trial for the treatment of AIDS) and (S)-HPMPC (good in vivo activity against HSV, VZV, CMV, and EBV). Oligonucleotides incorporating acyclic nucleosides at the 3'-and 5'-ends, or constituted of amino acyclic nucleosides, are resistant to cleavage by nucleases and may be useful in antisense and/or antigene therapy. HEPT is active against HIV-1: It binds in a hydrophic pocket on reverse transcriptase, rather than in the polymerase active site. Some acyclic nucleosides are potent inhibitors of purine and pyrimidine nucleoside phosphorylase. These compounds may have a therapeutic niche in combination therapy with antiviral and anticancer nucleosides, and in the treatment of diseases involving the T-cell.

2-Aminopurine

CYP2E1-mediated mechanism of anti-genotoxicity of the broccoli constituent sulforaphane.

The broccoli constituent sulforaphane (1-isothiocyanate-4-methylsulfinylbutane) has previously been shown to protect rats against 9,10-dimethyl-1,2-benz[a]anthracene tumorigenesis, thought to be due, at least in part, to induction of phase II detoxification. We investigated the ability of sulforaphane to also inhibit the phase I enzyme cytochrome P450 isoenzyme 2E1 (CYP2E1), which is responsible for activation of several carcinogens, including dialkylnitrosamines. Using the p-nitrophenol hydroxylation assay in microsomes from livers of acetone-treated Sprague-Dawley rats, sulforaphane was shown to be a potent competitive inhibitor of CYP2E1 with a Ki of 37.0 +/- 4.5 microM. In view of this result, we studied the capacity of sulforaphane to inhibit the genotoxicity of N-nitrosodimethylamine (NDMA). Sulforaphane at concentrations of > 0.8 microM inhibited the mutagenicity of NDMA (4.4 mg/plate) in Salmonella typhimurium strain TA100 after pre-incubation for 45 min with cytosol extract from livers of Balb/c mice pre-treated with acetone. Unscheduled DNA synthesis induced by NDMA (33.5 microM) in mouse hepatocytes was inhibited in a dose-dependent manner by sulforaphane at 0.064-20 microM. Sulforaphane was unable to inhibit mutagenicity of sodium azide (5 micrograms/plate), a direct acting mutagen, in the Salmonella assay. It was not itself genotoxic in hepatocytes, as measured by unscheduled DNA synthesis, or mutagenic in the strain of Salmonella employed and cytotoxic only at high concentrations (> or = 0.5 mM). These findings suggest that inhibition of CYP2E1 by sulforaphane may offer chemoprotection against carcinogenic substrates of this enzyme.

Animals

Physical and genetic mapping of chromosome 9S in maize using mutations with terminal deficiencies.

Deletion mapping was employed to determine the physical order of five morphological variants, pyd1, yg2, wd1, v28 and u31, with respect to restriction fragment length polymorphism (RFLP) markers located at the distal end of chromosome 9S in maize. The genetic materials used were a series of terminal-deficiency mutants, newly derived with McCLintock's original stocks developed in the 1940s, via breakage-fusion-bridge cycles. A combined physical map and genetic map has been constructed based on data gathered from both genetic complementation tests and RFLP analysis. The location of v31 in relation to RFLP markers was further determined by interval mapping. The physical distance between the healed telomeric end and the most distal RFLP marker in two terminal-deficiency lines was established by using pulsed field gel electrophoresis and verified by Bal31 digestion. The results from this study set a foundation for studies on the mechanism of healing of broken chromosome ends in higher plants.

Chromosome Mapping

The effect of acetylation and deacetylation on the disposition of dapsone and monoacetyl dapsone hydroxylamines in human erythrocytes in-vitro.

The fates of both dapsone and monoacetyl hydroxylamine have been studied in terms of acetylation and deacetylation within the human erythrocyte in-vitro. A comparison between the two metabolites showed equipotency in methaemoglobin generation at 15 min, although the monoacetyl derivative was the more rapid haemoglobin oxidizer. Within the erythrocytes, both dapsone and monoacetyl hydroxylamines were found to undergo acetylation, deacetylation and diacetylation. Of the inhibitors of acetylation studied, folate caused an increase in methaemoglobin formation associated with both metabolites, which led to a rise in both acetylated and non-acetylated amine formation. Amethopterin was associated with a rise in hydroxylamine mediated methaemoglobin formation which coincided with a fall in acetylated products. It is possible that the hydroxylamines undergo erythrocytic processes of acetylation and deacetylation before methaemoglobin-mediated reduction to their respective amines.

Acedapsone

Cloning maize telomeres by complementation in Saccharomyces cerevisiae.

Maize telomeric restriction fragments were cloned by virtue of their ability to function as telomeres on a linear plasmid in Saccharomyces cerevisiae. Nine maize telomeric YAC transformants (MTYs) were selected by hybridization to the Arabidopsis telomere repeat (CCCTAAA) from a pool of 1537 primary transformants. Bal31 digestion of MTY3 and MTY9 DNA indicated that the telomere hybridizing tracts are located at the terminus of the linear chromosome and therefore function as telomeres in yeast. Subclones generated for pMTY7 (pMTY7SC1) and pMTY9 (pMTY9ER) hybridized to Bal31 sensitive restriction fragments in maize DNA, indicating that maize telomeric restriction fragments had been cloned. Both pMTY7SC and pMTY9ER detected telomeric RFLPs, allowing the endpoints of seven chromosome arms to be determined. Additionally, pMTY7ER mapped to the centromeric regions of chromosomes 2 and 3, suggesting a relationship between centromeric and telomeric sequences. DNA sequencing of pMTY7SC and pMTY9ER revealed that both subclones contained CA-rich regions with sporadic occurrences of the telomere repeat and its degenerate repeats.

Base Sequence

Functional aspects of recollective experience in face recognition.

This article describes two experiments on awareness in recognition memory for novel faces. Two kinds of awareness, recollective experience and feelings of familiarity in the absence of recollective experience, were measured by "remember" and "know" responses. Experiment 1 showed that "remember" but not "know" responses were reduced by divided attention at study. Experiment 2 showed that massed versus spaced repetition of faces in the study list had opposite effects on "remember" and "know" responses. Massed repetition increased "know" responses and reduced "remember" responses. Spaced repetition increased "remember" responses and reduced "know" responses. The results of both experiments replicate previous findings from the verbal domain in the domain of face recognition, and hence they increase the ecological validity of this experimental approach to memory and awareness and the generality of its database. These findings are discussed from a rehearsal perspective on factors influencing the two states of awareness and in relation to the alternative "process dissociation" procedure.

Adult

Retrieval volition and memorial awareness in stem completion: an empirical analysis.

Facilitation in an incidental test of stem completion shows little influence of depth of processing at study, whereas facilitation in an opposition test (in which subjects give the first word coming to mind, but omit studied words) occurs following graphemic processing, but not following semantic processing. We argue that completions come to mind involuntarily in both tests. Involuntary conscious memory causes studied words to be omitted in an opposition test, but not in an incidental test, so that the difference in priming between tests is a measure of involuntary conscious memory. We obtained data consistent with this hypothesis by making overt the mental activities that occur covertly in an opposition test: (1) an on-line recognition measure in an incidental test showed a strong advantage of semantic over graphemic processing, even though depth of processing exerted little influence on priming; (2) conditionalizing on recognition failure resulted in accurate estimates of opposition performance; and (3) stems were completed much more rapidly in incidental and opposition tests than in an intentional test, in which voluntary retrieval was engaged. The data provide further evidence that retrieval volition (voluntary vs. involuntary) is dissociable from memorial state of awareness (conscious vs. unconscious). We contrast our approach with the process-dissociation approach, which confounds conscious awareness of the past with voluntary retrieval, overlooking involuntary conscious memory.

Adult

Recognition failure of categorised words: further evidence of exceptions.

When subjects study a list of B items paired with A items and are tested for recognition of the B items alone, and then for recall of the B items given the A items as cues, B items that can be recalled frequently go unrecognised. The extent of this recognition failure is predictable from a function discovered by Tulving and Wiseman (1975), which relates the probability of recognising the recallable items to the probability of recognising all items. Two kinds of exceptions to this function have been discovered: encoding exceptions and retrieval exceptions. Very few observations of retrieval exceptions exist. Four experiments described in this article provide further evidence that such exceptions occur when the B items are categorised and the A items are the names of the categories. According to a contextual account of the function and exceptions to it, these retrieval exceptions occur because the information provided by the A-item cues can be largely retrieved from the B items in the recognition test; hence, as cues, the A items do not provide much different contextual information to that provided by the B items. By this account, the function is an empirical law; exceptions fall outside the range of this law and define its boundary conditions.

Adolescent

Involuntary conscious memory and the method of opposition.

Priming in an indirect test of stem completion should reflect involuntary memory, but can be accompanied by conscious awareness of the past (involuntary conscious memory) or unaccompanied by such awareness (involuntary unconscious memory). We adapted the method of opposition developed by Jacoby, Woloshyn, and Kelley (1989) to obtain a measure of stem-completion priming that should reflect only involuntary unconscious memory. Subjects completed stems with the first word coming to mind, but wrote down a different word if the word that came to mind first had been previously encountered. Facilitatory priming was expected only when involuntary unconscious influences outweighed inhibitory effects of involuntary conscious memory, or of intentional retrieval. We observed a facilitation effect for items processed graphemically at encoding, in conjunction with an inhibition effect for items processed semantically at encoding. In contrast, a standard indirect test showed similar levels of priming following graphemic and semantic encoding, whereas a direct test showed a strong advantage of semantic over graphemic encoding. We argue that the two encoding activities produced approximately equivalent involuntary influences of memory, but that items encoded semantically were associated with involuntary conscious memory to a greater extent than were items encoded graphemically. Comparing indirect and opposition test performance can provide a quantitative index of relative levels of involuntary conscious and involuntary unconscious memory.

Analysis of Variance

Age differences in memory for prospective compared with retrospective subject-performed tasks.

In two experiments, younger and older adults studied three lists of verbal phrases, each of the latter describing a simple action. One list was studied and recalled verbally; one was recalled verbally, but the actions were performed at study [retrospective SPTs (subject-performed tasks)]; and one was studied verbally and the actions were performed at test (prospective SPTs). With long lists, but not with short ones, retrospective-SPT recall exceeded verbal recall and older adults recalled fewer SPTs than did younger adults. Prospective-SPT recall did not exceed verbal recall at either list length, and in each of these prospective-SPT tests, older adults recalled fewer action phrases than did younger adults. Thus, it appears that when retrospective and prospective tasks are equated there are marked age differences that are generally consistent with the view that memory impairment in the elderly is more likely to occur in tasks that make higher attentional processing demands.

Adolescent

Effects of lorazepam upon recollective experience in recognition memory.

The effects of lorazepam (2 mg) and placebo upon recognition memory with and without conscious recollection were assessed in a cross-over study with normal volunteers. When recognising a word from study lists presented before and 1, 3 and 5 h after drug administration, subjects were required to indicate whether they could consciously recollect the word's prior occurrence or recognised it on the basis of "knowing"; in the absence of conscious recollection. Lorazepam only impaired word recognition which was accompanied by conscious recollection, and further, the level of this impairment correlated significantly with each of three different indices of subjects' arousal at the time of presentation of each list. Recognition in the absence of conscious recollection was not impaired but somewhat heightened by lorazepam, and these effects did not significantly relate to any index of arousal. These findings are interpreted as providing further support for the notion that recognition entails two distinct components, one based on contextual and associative information and related to conscious recollection, the other possibly based on a "traceless" perceptual or semantic memory system and related to feelings of knowing in the absence of conscious recollection. Implications are drawn for a contextual-encoding/retrieval account of lorazepam-induced amnesia.

Adult

Mathematical constraints and the Tulving-Wiseman law: a rejoinder.

Hintzman (1991; 1992) has claimed that the reason data points approximate the recognition failure function discovered by Tulving and Wiseman (1975) is that they are mathematically constrained to do so, and the reason that a few data points do not approximate the function, but are exceptions to it, is that these data points are less subject to mathematical constraints. He has additionally argued that such exceptions are more likely with low levels of recall and strong underlying sources of positive covariance. We provide empirical evidence relevant to this mathematical model using 301 observations from a database of all relevant experimental conditions published between 1973 and 1992 (Nilsson & Gardiner, 1993). We conclude that mathematical constraints have only a minor influence on the function, not the causal role assigned to them in Hintzman's (1992) model. By our account, both the function and exceptions to it reflect a single psychological principle, the functional effectiveness of contextual cues.

Cues