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D L Nelson

Publications and source records attributed to D L Nelson.

At least 217 records · Page 12Linked to original sources
PubMed1993

Implicit memory: effects of network size and interconnectivity on cued recall.

Previous findings have indicated that the recall of a recently studied word is affected by how many associates it has in long-term memory (set size). The purpose of these experiments was to determine whether recall is also affected by the connectivity of these associates. Studied words were preselected to represent combinations of set size and connectivity and, in different experiments, recall was cued with extralist or intralist cues and with cues sharing few or many associates with the studied words. Effects of study time, encoding context, and levels of processing were also investigated. The results indicated that recall was more likely for words with smaller associative sets and for words with more interconnected sets of associates. These findings demonstrate that the recall of a recently presented word in the presence of a retrieval cue is affected by both the size and organization of its implicitly activated associative structure.

Association↗
PubMed1993

Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome.

We have performed mRNA in situ hybridization studies and northern blot analysis in the mouse and human, respectively, to determine the normal gene expression patterns of FMR-1. Expression in the adult mouse was localized to several regions of the brain and the tubules of the testes, which are two of the major organs affected in fragile X syndrome. Universal and very strong expression was observed in early mouse embryos, with differentially decreasing expression during subsequent stages of embryonic development. The early embryonic onset and tissue specificity of FMR-1 gene expression is consistent with involvement in the fragile X phenotype, and also suggests additional organ systems in which clinical manifestations of reduced FMR-1 gene expression may occur.

Adult↗
PubMed1993

Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat.

Fragile X syndrome is associated with massive expansion of a CGG trinucleotide repeat within the FMR-1 gene and transcriptional silencing of the gene due to abnormal methylation. Partial cDNA sequence of the human FMR-1 has been reported. We report here the isolation and characterization of cDNA clones encoding the murine homologue, fmr-1, which exhibit marked sequence identity with the human gene, including the conservation of the CGG repeat. A conserved ATG downstream of the CGG repeat in human and mouse and an in-frame stop codon in other human 5' cDNA sequences demarcate the FMR-1 coding region and confine the CGG repeat to the 5' untranslated region. We also present evidence for alternative splicing of the FMR-1 gene in mouse and human brain and show that one of these splicing events alters the FMR-1 reading frame, predicting isoforms with novel carboxy termini.

Alternative Splicing↗
PubMed1993

High resolution methylation analysis of the FMR1 gene trinucleotide repeat region in fragile X syndrome.

Fragile X syndrome is the most common form of inherited mental retardation in man. The disease is associated with expansion in the number of tandem CGG trinucleotide repeats in the 5' untranslated region of the human FMR1 gene. Transmitting males, individuals who are unaffected carriers of the disease, show a moderate increase in the number of repeat units, while fully penetrant males show a major expansion in repeat number. Major expansion of the repeat in affected males is correlated with methylation of certain restriction enzyme recognition sites in the 5' CpG island containing the trinucleotide repeat in these patients. Phenotypic expression of the mutation appears to be due to transcriptional silencing of the FMR1 gene. We now report direct high resolution methylation analysis of the trinucleotide repeat and its flanking regions using ligation-mediated PCR genomic sequencing. We find the cytosine residue of all CpG dinucleotides examined within and surrounding the FMR1 trinucleotide repeat to be unmethylated in the DNA of normal male leukocytes and transmitting male lymphoblasts; these same cytosines are methylated in affected male lymphoblasts, in a somatic cell hybrid containing a fragile X chromosome from an affected male, and in a somatic cell hybrid containing a normal inactive X chromosome. The methylation pattern of the FMR1 5' CpG island in affected patients as determined by genomic sequencing is remarkably similar to that seen for the X-linked human phosphoglycerate kinase and hypoxanthine phosphoribosyltransferase gene 5' CpG islands on the inactive human X chromosome.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Methylcytosine↗
PubMed1993

Regional assignment of 19 X-linked ESTs.

Subchromosomal localizations for 19 X-linked expressed sequence tags (ESTs) have been determined. Two ESTs are located in Xq28, adding two novel genes to this disease-rich region. The remaining ESTs are located primarily in the pericentromeric region, with most mapping to Xp11.1-p21.1. YAC and cosmid genomic clones have been isolated for several of these loci. Available cDNAs have been used to characterize the corresponding transcripts by Northern analysis in multiple human tissues.

Blotting, Northern↗
PubMed1993

Alternative splicing in the fragile X gene FMR1.

The FMR1 gene, associated with fragile X syndrome, has recently been cloned and the sequence of partial cDNA clones is known. We have determined additional cDNA sequences both at the 5' and 3' end. We have characterized the expressed gene by means of RT-PCR in various tissues and have found that alternative splicing takes place in the FMR1 gene, which does not seem to be tissue specific. When the different alternative splicing events are combined, 12 distinct mRNA products could result from FMR1 expression in each tested tissue. In all these transcripts the open reading frame is maintained until the same stop codon. At the 3' end alternative use of polyadenylation signals is found. The alternative splicing allows functional diversity of the FMR-1 gene. Whether all the possible proteins will be synthesized and whether they will be functionally active has to be determined.

Alternative Splicing↗
PubMed1993

Fine structure of the human FMR1 gene.

The fragile X syndrome is due to a CGG triplet expansion in the first exon of FMR1, resulting in hypermethylation and extinction of gene expression. To further our understanding of the gene's involvement in the syndrome, we report the physical structure of this locus. A high resolution restriction map of the FRAX(A) locus has been prepared encompassing approximately 50 kb. Using exon-exon PCR and restriction analysis, the FMR1 gene has been determined to consist of 17 exons spanning 38 kb of Xq27.3. Each intron-exon boundary has been sequenced. In general, the splice donors and acceptors located in the 5' portion of the gene demonstrate greater adherence to consensus than those in the 3' end, providing a possible explanation for the finding of alternative splicing in FMR1. The elucidation of the exon composition of the FMR1 gene and its flanking region will enhance detection of coding sequence mutations possible in fragile X phenocopy individuals.

Alternative Splicing↗
PubMed1993

Direct versus indirect molecular diagnosis of fragile X mental retardation in 40 German families at risk.

In order to test whether the direct molecular diagnostic approach for fragile X mental retardation (Martin-Bell syndrome, MBS) really makes diagnosis of this disease more precise, we evaluated the results of direct diagnosis in 40 German families at risk together with the results of an earlier study with closely linked flanking markers in the same families. Of 84 men analysed, 43 showed clinical signs. In 39 of these affected men the disease could be confirmed by direct diagnosis. Compared to cytogenetic data, one man was false negative and two were false positive. Two men, whose status could not be determined by means of RFLP data, proved to be normal transmitting males (NTMs). However, the possibility of being an NTM had to be rejected in one case on RFLP data. Fragile X syndrome could be confirmed in 10 of the 13 women with clinical signs. Compared to cytogenetic data there were three cases of false negative results and one of false positive. All 36 obligate carrier women were detected by the direct approach. In addition, 22 women were newly identified as normal transmitting females (NTFs), among them one woman who could not be identified by cytogenetic means or by analysis with closely linked markers. These findings are discussed in view of the relative reliability of the three diagnostic approaches to MBS. Special attention is drawn to the significance of false negative and false positive results in direct diagnosis.

Base Sequence↗
PubMed1993

Physical mapping of Xq24-25 around loci closely linked to the X-linked lymphoproliferative syndrome locus: an overlapping YAC map and linkage between DXS12, DXS42, and DXS37.

We have localized several markers in the Xq24-25 region containing DXS12, DXS42 and DXS37 which are closely linked to the X-linked lymphoproliferative syndrome (XLP) locus. A 850-kb restriction map has been established by mapping overlapping YACs and showed that DXS12 and DXS42 are physically linked within about 50 kb. DXS37 is separated from these two loci at a maximum distance of 3,700 kb. Several new probes have been generated which will contribute to further physical mapping of this region.

Chromosome Walking↗
PubMed1993

Parameters affecting the development of non-Hodgkin's lymphoma in patients with severe human immunodeficiency virus infection receiving antiretroviral therapy.

PURPOSE: To investigate the occurrence of non-Hodgkin's lymphoma (NHL) in human immunodeficiency virus (HIV)-infected patients receiving long-term antiretroviral therapy and factors associated with the development of these lymphomas. PATIENTS AND METHODS: The charts of 55 patients with advanced HIV infection receiving zidovudine (formerly known as azidothymidine [AZT])-based therapy and 61 patients receiving dideoxyinosine (ddI) were examined for the occurrence of NHL. Stored samples from the AZT-based treatment cohort were examined retrospectively for parameters predictive of the subsequent development of lymphoma. RESULTS: Eight of 55 patients receiving AZT-based therapy developed NHL, yielding an estimated probability of 12% (95% confidence interval [CI], 4.7% to 27.1%) after 24 months, and 29.2% (95% CI, 15.2% to 48.7%) after 36 months. Four of 61 patients receiving ddI developed NHL, yielding a 6.2% (95% CI, 2.1% to 17%) estimated probability after 24 months, and 9.5% (95% CI, 3.6% to 22.8%) after 36 months. The difference between these cohorts was not significant (two-tailed P [P2] = .13). Patients with less than 50 CD4 cells/microL developed NHL at a significantly higher rate (P2 = .0085). This was particularly true for patients who presented with primary CNS lymphoma (PCNSL). For patients receiving AZT-based therapy, pretreatment serum interleukin-6 (IL-6) levels were somewhat higher in those who subsequently developed NHL than in those who did not (P2 = .048). CONCLUSION: HIV-infected patients with profound immunodeficiency, especially those with less than 50 CD4 cells/microL, are at substantial risk of developing NHL and particularly PCNSL. Additional studies are needed to define the role of other factors such as IL-6 in the pathogenesis of these opportunistic tumors.

CD4-Positive T-Lymphocytes↗
PubMed1993

In vitro phosphorylation of ciliary dyneins by protein kinases from Paramecium.

Paramecium dyneins were tested as substrates for phosphorylation by cAMP-dependent protein kinase, cGMP-dependent protein kinase, and two Ca(2+)-dependent protein kinases that were partially purified from Paramecium extracts. Only cAMP-dependent protein kinase caused significant phosphorylation. The major phosphorylated species was a 29 kDa protein that was present in both 22 S and 12 S dyneins; its phosphate-accepting activity peaked with 22 S dynein. In vitro phosphorylation was maximal at five minutes, then decreased. This decrease in phosphorylation was inhibited by the addition of vanadate or NaF. The 29 kDa protein was not phosphorylated by a heterologous cAMP-dependent protein kinase, the bovine catalytic subunit. Phosphorylation of dynein did not change its ATPase activity. In sucrose gradient fractions from the last step of dynein purification, phosphorylation by an endogenous kinase occurred. This phosphorylation could not be attributed to the small amounts of cAMP- and cGMP-dependent protein kinases known to be present, nor was it Ca(2+)-dependent. This previously uncharacterized ciliary protein kinase used casein as an in vitro substrate.

Animals↗
PubMed1993

The use of a game to promote arm reach in persons with traumatic brain injury.

This study tested a principle of occupational therapy and motor learning theory in the context of neurodevelopmental treatment techniques. Ten trials of occupationally embedded intervention (playing Simon, a computer-controlled game) were compared with 10 trials of rote arm-reach exercise. A counterbalanced design was structured so that each subject experienced each condition one week apart. Subjects were 17 men and 3 women with traumatic brain injury who exhibited mild to moderate spasticity in the upper extremity. Maximum distance from hip to wrist during active reach of the affected extremity was measured by digitization of videotape with the Motion Analysis EV-3D system. Results indicated that the use of the game elicited significantly more range of motion than the rote exercise (t (19) = 5.77, p < .001). These results support the use of an occupationally embedded intervention for persons with traumatic brain injury and add to the theoretical base of occupational therapy.

Adult↗
PubMed1993

The effects of options on performance of an art project in adults with mental disabilities.

The relationships among the presence of options, interest, preference, choice, meaning, purpose, and performance in occupation are central to occupational therapy knowledge. This study examined whether giving adults with mental disabilities options at the beginning of an art occupation would motivate them to paint more than when not given options. The sample consisted of 13 men and 9 women; ages ranged from 24 to 76. The subjects were yoked in pairs. One subject from each pair was given a choice of which of five ceramic objects to paint. The second subject was instructed to paint the same type of object that the first subject had chosen. Three days to 1 week later, roles were reversed. The number of times the subject applied the paint to the object after dipping the brush into paint was recorded by the researcher. Each subject was also timed with a stopwatch from the first time paint was applied to the time the subject indicated completion of the activity. The Wilcoxon matched-pairs signed-ranks test revealed that subjects painted significantly more (Z = 2.9, p < .01) when they had a choice than when they did not have a choice.

Adult↗
PubMed1993

Use of uniform terminology by occupational therapists.

Uniform Terminology for Occupational Therapy-Second Edition (American Occupational Therapy Association, 1989b) was published to foster consistency in terminology among occupational therapists. In this study, agreement between occupational therapists and Uniform Terminology about the definition and categorization of 15 terms was examined. Agreement was measured on 113 responses from a randomly selected sample of 180 occupational therapists. Low levels of agreement were found on both definition of terms (71.9 mean percentage of agreement, SD = 12.4) and categorization of terms into larger conceptual categories (34.9 mean percentage of agreement, SD = 11.7). Therapists selected an alternative definition more often than the one given by Uniform Terminology on 2 of 15 terms and selected an alternative categorization more often than the one given in Uniform Terminology on 8 of 15 terms. These results indicate that therapists do not agree with many Uniform Terminology definitions and categorizations.

Humans↗
PubMed1993

Preclinical studies on LY228729: a potent and selective serotonin1A agonist.

LY228729 is a conformationally restricted tryptamine derivative with a carboxamide serving as a protophilic group to mimic the hydroxyl in serotonin (5-HT). LY228729 has high affinity for the 5-HT1A receptor, weak affinity for the 5-HT1D receptor and no significant affinity for other monoaminergic receptors studied. LY228729 was less effective than 5-carboxamidotrytamine in suppressing K(+)-evoked release of 3H-5-HT from parietal-occipital cortical slices from guinea pigs, which is in agreement with its weak 5-HT1D receptor affinity. LY228729 reduced hypothalamic 5-hydroxyindole-3-acetic acid levels and increased serum corticosterone levels in rats. LY228729 reduced hypothalamic 5-hydroxytryptophan accumulation after decarboxylase inhibition. LY228729 increased flat posture and lower lip retraction scores in rats at doses between 0.1 and 1 mg/kg s.c. (p.o. doses were 10 times higher) and these effects were blocked by (+/-) pindolol. LY228729 induced a hypothermic response in rats, which was blocked by (+/-) pindolol. These in vivo responses are characteristics of compounds with 5-HT1A agonist activity. In the preclinical efficacy models, LY228729 suppressed motion sickness responses in cats; decreased ejaculatory latency and the increased copulatory efficiency and rate in rats and increased punished responding at lower doses than it lowered unpunished responding in rats. Collectively, these results indicate that LY228729 is potent 5-HT1A agonist with bioavailability properties sufficient for clinical evaluation and with efficacy in preclinical models of anxiety, sexual disorders and motion sickness. Since the 5-HT1A agonists that have been studied previously have antidepressant activity, this indication will also be evaluated.

Animals↗