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Biomedical subjects

U Olofsson

Publications and source records attributed to U Olofsson.

11 recordsLinked to original sources

The western Swedish BRCA1 founder mutation 3171ins5; a 3.7 cM conserved haplotype of today is a reminiscence of a 1500-year-old mutation.

The most recurrent BRCA1/BRCA2 mutation in Sweden is the BRCA1 mutation 3171ins5. In the western part of Sweden this mutation accounts for as much as 77% of identified mutations in these two genes. Our aim was to analyse in detail the haplotype and founder effects of the 3171ins5 and furthermore attempt to estimate the time of origin of the mutation. In the study we included eighteen apparently unrelated families with hereditary breast and/or ovarian cancer. At least one individual in each family had previously tested positive for the 3171ins5 mutation. Polymorphic microsatellite markers were used for the haplotype analyses. The markers were located within or flanking the BRCA1 gene spanning a region of 17.3 cM. We found several different haplotypes both for disease alleles and for the normal alleles. However, a conserved haplotype of 3.7 cM was observed in the 3171ins5 carriers spanning over four markers located within or very close to the BRCA1 gene. As this haplotype was not present in any of the normal controls it is highly likely that this is a mutation identical by descent, i.e. a true founder. The results from the haplotype analyses were used to estimate the age of the mutation. Estimations based on the P(excess) and linkage disequilibrium gives a first appearance of the mutation sometime around the 6th century, approximately 50 generations ago.

BRCA1 Protein↗

Characterization of MK-801-induced behavior as a putative rat model of psychosis.

The objective of this study was to characterize the behavior induced by the N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine maleate) in rats as a model of psychosis. The temporal profile, dose dependence, age, and sex differences of the behavior are described. A gas chromatographic method for the analysis of MK-801 in plasma and brain was developed. Female rats showed 4 to 10 times more MK-801-induced behavior and displayed around 25 times higher serum and brain concentrations of MK-801 than male rats. Twenty-one neuroactive compounds, including a number of excitatory amino acid-active substances, were tested for the effect on MK-801-induced behavior. Neuroleptics blocked MK-801-induced behavior in a dose-dependent manner that correlated to their antipsychotic potency in humans. Adenosine receptor agonists and an N-methyl-D-aspartate receptor-associated glycine site antagonist showed putative antipsychotic effects. In conclusion, MK-801-induced behavior represents a rat excitatory amino acid hypofunction model of psychosis that appears to be of clinical relevance and may be of value in the search for new antipsychotic agents.

Aging↗

Win some, lose some: hypermnesia for actions reflects increased item-specific processing.

Memory for simple action phrases (e.g., "Break a match") improves when subjects perform the actions at study. The relative contribution of item-specific and relational processing to this enactment effect has been an issue of considerable debate. It was addressed in the present study by examining hypermnesia in a multiple-test free recall paradigm, based on the assumptions that item-specific processing increases the probability of interest gains and relational processing protects against interest forgetting (e.g., Burns, 1993; Klein, Loftus, Kihlstrom, & Aseron, 1989). It was found that the enactment condition produced both significantly more gains and more losses than did the nonenactment condition, resulting in a net gain (hypermnesia) for the enactment condition. The results suggest that enactment promotes item-specific processing at the expense of relational processing.

Adult↗

The effect of enactment on memory for order.

The effect of enactment on memory for serial order was investigated in two experiments. In both experiments a reconstruction task was used to separate order from item information. In Experiment 1 enactment and test information was manipulated between groups. For subjects who had not been informed about the reconstruction test, performance of verbal and motor groups was similar with regard to both serial-position curves and overall performance. For subjects who knew beforehand that they would be tested for memory of the order of the action events, performance in the verbal condition was significantly better than in the motor condition. In Experiment 2, the reversed enactment effect for test-informed subjects was replicated with a within-subjects design. The results agree with Engelkamp and Zimmer's (1984, 1994) position that enactment serves exclusively to enhance item information, and indicate that subjects have less control over the encoding processes when they are enacting than during verbal encoding (cf. Cohen, 1981).

Adult↗

Age differences in episodic memory, semantic memory, and priming: relationships to demographic, intellectual, and biological factors.

This study examined age differences in episodic memory, semantic memory, and priming using a random sample of 1,000 men and women from 10 age groups (35, 40, 45, . . . 80 years). The main purpose was to determine whether an age effect existed after differences on various demographic, intellectual, and biological factors had been controlled for. The simple correlations of age with episodic and semantic memory performance were found to be significant, whereas no relationship was found between age and levels of priming. After controlling for differences on the background factors, age predicted episodic but not semantic memory performance. It is proposed that the failure to account for the age effect on episodic memory is because it is caused by age-related neuronal changes.

Adult↗

Determinants of word fragment completion.

A current debate in the memory literature concerns the validity of word fragment completion (WFC) as a test of implicit memory. It has been claimed that language variables exert a strong influence on the task, and that the task reflects memory only to a small extent (Hintzman & Hartry, 1990). For these reasons, the use of contingency analyses of recognition and WFC performance as a means of studying underlying memory processes has been criticized. The present study addressed this issue by examining the influence of language variables on completion of a set of computer generated single-solution fragments of Swedish words (Olofsson & Nyberg, 1992). It was found that language variables indeed had a large effect on completion performance, and that priming only accounted for a small portion of variance in the task. It is therefore suggested that the method of triangulation should be employed for contingency analyses involving WFC.

Adult↗

The generation effect in primed word-fragment completion reexamined.

Two experiments were designed to test a claim made by Gardiner (1988) that there are generation effects in implicit memory as measured by word-fragment completion. Subjects either read words at study or generated the words from fragments. As in previous research, fragments were completed to a greater extent if they were identical at study and test than if they differed. In Experiment 1 it was found that subjects could recognize explicitly the exact form of fragments that had been used for self-generation and distinguish these from other forms of fragments. An analysis of the contingency relations between recognition of fragments and fragment completion showed a high degree of dependence between the two tests. In Experiment 2 it was found that the match of surface features between study and test was a necessary, but not sufficient, condition to produce enhancement of priming. The results are interpreted as supporting the claim that generation does involve a data-driven component in addition to semantic elaboration.

Adolescent↗

Swedish norms for completion of word stems and unique word fragments.

Swedish norms for completion of word stems and single-solution word fragments, with few or many letters specified, were obtained from Swedish students. Comparisons were made for completion rates between stems and fragments that were possible to complete with the same word. As expected, completion rates for fragments were generally superior to those of word stems since the word stems allowed alternative completions. Adding one letter to the word stems and fragments resulted in a significant increase in the probability of completion, for both stems and fragments. A stepwise regression analysis was conducted in order to partial out factors determining the completion probability for fragments. The ratio of specified letters to blank characters, and the familiarity of the solution was found to be the most important factors. Finally, the effect of number of given letters in the word stem on the number of generated words per stem was studied. The mean number of words generated per stem was found to be equal for both two- and three-letter word stems.

Adolescent↗

Clinical and metabolic features of ethanol-methanol poisoning in chronic alcoholics.

The kinetics of methanol were examined in 84 chronic alcoholics admitted after drinking a cleansing solution containing 90% ethanol and 5% methanol. On admission, the average blood methanol concentration was 20 mmol/l (64 mg/dl) and blood ethanol concentration was 39 mmol/l (179 mg/dl). Although these patients were not treated with ethanol, and methanol concentrations remained high as blood ethanol concentrations fell to zero, no acidosis or other signs of classic methanol poisoning developed. The rate of metabolism of methanol was correlated to the initial ethanol concentration. To avoid unnecessary invasive therapy, treatment of methanol poisoning should be based on the case history, clinical signs, and laboratory features-not solely on blood methanol concentrations.

Adult↗

Total plasma concentrations, red blood cell concentrations, and radioreceptor assay values compared with unbound plasma concentrations of thioridazine and thioridazine metabolites in psychiatric patients.

Neuroleptic drug concentrations at the receptor sites are likely to be reflected more closely by the unbound than by the total plasma concentrations. The aim of this study was to establish whether or not the unbound plasma concentrations of thioridazine and its main nonconjugated metabolites show a stronger correlation to the red blood cell (RBC) concentration than to the total plasma concentration of the drug. The total and unbound plasma concentrations and the RBC concentrations of thioridazine and its metabolites were therefore determined in thioridazine-treated patients. "Calculated unbound concentration values" were derived from the determined total concentrations of the drug, the concentrations of drug-binding proteins, and previously determined kappa values. Since the RBC concentrations showed the best correlation to the unbound plasma values, they may be a more accurate tool than the total plasma concentrations for monitoring thioridazine treatment. The determined unbound plasma concentrations were better correlated to the calculated unbound concentrations than to the total plasma concentrations. The total plasma concentrations, but neither the unbound plasma nor the RBC concentrations, were significantly correlated to the concentrations of the drug-binding protein alpha 1-acid glycoprotein. Radioreceptor assay values were strongly correlated to the weighted sum of the total and unbound plasma concentrations of thioridazine and its metabolites.

Adolescent↗

Effects of division of attention during encoding and retrieval on age differences in episodic memory.

This study examined the effects of dual task requirements on age differences in free recall performance. One thousand adults ranging in age between 35 and 80 years performed a word recall task alone and concurrently with a card-sorting task (at encoding, retrieval, or both). Age differences in memory performance were substantial under single task conditions, but after correcting memory performance under dual task conditions for differences in single task performance, age did not predict performance. These results do not support the hypothesis that reduced attentional capacity in old age is underlying age differences in episodic memory.

Adult↗