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Biomedical subjects

D L Nelson

Publications and source records attributed to D L Nelson.

At least 109 records · Page 6Linked to original sources
PubMed1998

Eliciting functional extension in prone through the use of a game.

OBJECTIVE: Although occupationally embedded exercise is becoming a recognized topic in occupational therapy research, study of this phenomenon in children has been limited. The present study examined whether play elicits therapeutic patterns of movement through the use of two ABA single-case experiments. It was predicted that in two children with hypotonic cerebral palsy, the addition of a favorite game to the occupational form, or treatment environment, would increase functional vertical neck and back extension. METHOD: Each subject was positioned in prone on a wedge. During the A phases, each was given verbal directions to hold her head up. During the B phase, a favorite game was introduced. It was predicted that each subject would extend her back and neck in a functional way in order to manipulate and observe the game. The dependent variables were the mean range of neck extension and the mean range of back extension, which were measured by a videotaped, two-dimensional kinematic analysis. RESULTS: The addition of a favorite game to the occupational form improved vertical neck and back extension while discouraging nonfunctional neck hyperextension and fixing postures in both children. CONCLUSION: Embedding exercise within a play occupation enhanced the prone extension of two children with hypotonic cerebral palsy.

Cerebral Palsy↗
PubMed1998

The roles of cue and target familiarity in making feeling of knowing judgments.

This study evaluated the effects of cue and target familiarity on metacognitive judgments by using a retroactive interference paradigm. Subjects studied 12 pairs of unrelated words. The first 6 pairs formed an A-B list, and the next 6 formed an A-B list (both elements repeated), a C-B list (only the target repeated), an A-D list (only the cue repeated), or a C-D list (neither element repeated). Following study, the six critical cues were presented and subjects made predictions of knowing. Predictions were highest when both elements were repeated and equally low when only the cue, only the target, or neither element was repeated. A subsequent cued recall test showed that significant retroactive interference effects were apparent. The findings suggest that neither cue nor target familiarity alone sufficiently explains knowing judgments.

Cognition↗
PubMed1998

Multiple subtypes of serotonin receptors are expressed in rat sensory neurons in culture.

[3H]5-HT revealed the presence of serotonin receptors in cultured rat sensory neurons. [3H]5-CT binding was inhibited by cyanopindolol with an IC50 of 0.87 +/- 0.30 nM, suggesting the expression of the 5-HT1B receptor in these neurons. The presence of 5-HT1B receptors was confirmed by the displacement of [125I]Iodocyanopindolol binding by cyanopindolol with an IC50 of 2.43 +/- 0.81 nM. 5-HT1B receptors are the predominant type of serotonin receptors labeled by [3H]5-HT in cultured DRG neurons, representing approximately 60% of the specific [3H]5-HT binding sites. In addition, 5-HT1D and 5-HT2A receptor binding was also found in these neurons. RT-PCR analysis of RNA isolated from embryonic sensory neurons in culture confirmed the expression of 5-HT1B, 5-HT1D and 5-HT2A receptor mRNA. It also demonstrated the presence of 5-HT1F, 5-HT2C, 5-HT3, 5-HT4, 5-HT5A and 5-HT5B receptor mRNA and the absence of 5-HT1A, 5-HT1E, 5-HT2B, 5-HT6 and 5-HT7 mRNA. The identification of multiple subtypes of serotonin receptors expressed in cultured embryonic sensory neurons suggests that DRG neuronal cultures may be an excellent model to examine the direct effects of serotonin on the activity of these sensory neurons.

Animals↗
PubMed1997

Mutations of transmembrane IV and V serines indicate that all tryptamines do not bind to the rat 5-HT2A receptor in the same manner.

Two mutations of the rat serotonin 5-HT2A receptor were made, expressed and examined for their ability to bind and be stimulated by certain tryptamines as well as their ability to bind antagonists. Mutation of Ser207 to an Ala (S207A) resulted in no substantial changes in binding of either 5-HT2A antagonists or agonists. In contrast, mutation of Ser239 to an Ala (S239A) resulted in significant changes in the 5-HT2A receptor with some but not all agonists and antagonists examined. Specifically, 5-HT had decreased affinity for the S239A mutated 5-HT2A receptor, showing over a 10-fold decrease in receptor-binding displacement, while still being capable of stimulating IP3 formation. However, the agonists tryptamine, 5-methoxytryptamine (5-MeOT), and N-1-isopropyl-5-methoxytryptamine; and the antagonists ketanserin, LY 86057, and LY 53857 were significantly less affected by a S239A mutation. These results suggest that while 5-HT might have a direct interaction with the Ser239 of the 5-HT2A receptor, tryptamine and 5-MeOT interact with this receptor in a different manner.

Amino Acid Sequence↗
PubMed1997

Dihydrobenzofuran analogues of hallucinogens. 4. Mescaline derivatives.

Dihydrobenzofuran and tetrahydrobenzodifuran functionalities were employed as conformationally restricted bioisosteres of the aromatic methoxy groups in the prototypical hallucinogen, mescaline (1). Thus, 4-(2-aminoethyl)-6,7-dimethoxy-2,3-dihydrobenzofuran hydrochloride (8) and 1-(8-methoxy-2,3,5,6-tetrahydrobenzo[1,2-b:5,4-b']difuran-4-yl)-2- aminoethane hydrochloride (9) were prepared and evaluated along with 1 for activity in the two-lever drug discrimination (DD) paradigm in rats trained to discriminate saline from LSD tartrate (0.08 mg/kg). Also, 1, 8, and 9 were assayed for their ability to displace [3H]ketanserin from rat cortical homogenate 5-HT2A receptors and [3H]8-OH-DPAT from rat hippocampal homogenate 5-HT1A receptors. In addition, these compounds were evaluated for their ability to compete for agonist and antagonist binding to cells expressing cloned human 5-HT2A, 5-HT2B, and 5-HT2C receptors. Finally, agonist efficacy was assessed by measurement of phosphoinositide hydrolysis in NIH 3T3 cells expressing the rat 5-HT2A or 5-HT2C receptors. Although 1 fully substituted for LSD in the DD assays (ED50 = 33.5 mumol/kg), neither 8 nor 9 substituted for LSD, with just 50% of the rats administered 8 selecting the drug lever, and only 29% of the rats administered 9 selecting the drug lever. All of the test compounds had micromolar affinity for the 5-HT1A and 5-HT2A receptors in rat brain homogenate. Curiously, the rank order of affinities of the compounds at 5-HT2A sites was opposite their order of potency in the behavioral assay. An evaluation for ability to stimulate phosphoinositide turnover as a measure of functional efficacy revealed that all the compounds were of approximately equal efficacy to serotonin in 5-HT2C receptors. At 5-HT2A receptors, however, 8 and 9 were significantly less efficacious, eliciting only 61 and 45%, respectively, of the maximal response. These results are consistent with the proposed mechanism of action for phenethylamine hallucinogens, that such compounds must be full agonists at the 5-HT2A receptor subtype. In contrast to the 2,5-dimethoxy-substituted phenethylamines, where rigidification of the methoxy groups had no deleterious effect on activity, the loss of activity in the 3,4,5-trioxygenated mescaline analogues may suggest that the 3 and 5 methoxy groups must remain conformationally mobile to enable receptor activation.

3T3 Cells↗
PubMed1997

Extracellular GTP causes membrane-potential oscillations through the parallel activation of Mg2+ and Na+ currents in Paramecium tetraurelia.

Paramecium tetraurelia responds to extracellular GTP (>/= 10 nm) with repeated episodes of prolonged backward swimming. These backward swimming events cause repulsion from the stimulus and are the behavioral consequence of an oscillating membrane depolarization. Ion substitution experiments showed that either Mg2+ or Na+ could support these responses in wild-type cells, with increasing concentrations of either cation increasing the extent of backward swimming. Applying GTP to cells under voltage clamp elicited oscillating inward currents with a periodicity similar to that of the membrane-potential and behavioral responses. These currents were also Mg2+- and Na+-dependent, suggesting that GTP acts through Mg2+-specific (IMg) and Na+-specific (INa) conductances that have been described previously in Paramecium. This suggestion is strengthened by the finding that Mg2+ failed to support normal behavioral or electrophysiological responses to GTP in a mutant that specifically lacks IMg ("eccentric"), while Na+ failed to support GTP responses in "fast-2," a mutant that specifically lacks INa. Both mutants responded normally to GTP if the alternative cation was provided. As IMg and INa are both Ca2+-dependent currents, the characteristic GTP behavior could result from oscillations in intracellular Ca2+ concentration. Indeed, applying GTP to cells in the absence of either Mg2+ or Na+ revealed a minor inward current with a periodicity similar to that of the depolarizations. This current persisted when known voltage-dependent Ca2+ currents were blocked pharmacologically or genetically, which implies that it may represent the activation of a novel purinergic-receptor-coupled Ca2+ conductance.

Animals↗
PubMed1997

A yeast artificial chromosome (YAC) contig encompassing the critical region of the X-linked lymphoproliferative disease (XLP) locus.

X-linked lymphoproliferative disease (XLP) is characterized by a marked vulnerability to Epstein-Barr virus (EBV) infection. Infection of XLP patients with EBV invariably results in fatal mononucleosis, agammaglobulinemia, or malignant lymphoma. Initially the XLP gene was assigned to a 10-cM region in Xq25 between DXS42 and DXS37. Subsequently, an interstitial, cytogenetically visible deletion in Xq25 was identified in one XLP family, 43. In this study we estimated the deletion in XLP patient 43-004 by dual-laser flow karyotyping to involve 2% of the X chromosome, or approximately 3 Mb of DNA sequence. From a human chromosome Xq25-specific yeast artificial chromosome (YAC) sublibrary, five YACs containing DNA sequences deleted in patient 43-004 have been isolated. Sequence-tagged sites (STSs) from these YACs have been used to identify interstitial deletions in unrelated XLP patients. Three more families with interstitial deletions were found. Two of the patients (63-003 and 73-032) carried an interstitial deletion of 3.0 Mb overlapping the 43-004 deletion. In one XLP patient (30-011) who exhibited the characteristic postinfectious mononucleosis phenotype of XLP with hypogammaglobulinemia and malignant lymphoma, a deletion of approximately 250 kb was detected overlapping the deletion detected in patients 43-004, 63-003, and 73-032. A YAC contig of 2.2 Mb spanning the XLP critical region, whose orientation on chromosome X was determined by double-color fluorescence in situ hybridization and which consists of 15 overlapping YAC clones, has been constructed. A detailed restriction enzyme map of the region has been constructed. YAC insert sizes were determined by counter-clamped homogenous electric field gel electrophoresis. Chimerism of YACs was determined by FISH and restriction mapping. On the basis of lambda subclones, YAC end-derived plasmids, and STSs with an average spacing of 100 kb, a long-range physical map was constructed using 5 rare-cutter restriction enzymes. The STSs and lambda subclones were used in Southern hybridization and PCR analyses. The work presented here substantially refines the critical region for XLP. The YAC contig with the overlapping interstitial deletions constitutes the basis for the construction of a transcriptional map of the critical region and facilitates the identification of the XLP gene.

Chromosomes, Artificial, Yeast↗
PubMed1997

Characterization of LY344864 as a pharmacological tool to study 5-HT1F receptors: binding affinities, brain penetration and activity in the neurogenic dural inflammation model of migraine.

LY344864 is a selective receptor agonist with an affinity of 6 nM (Ki) at the recently cloned 5-HT1F receptor. It possesses little affinity for the 56 other serotonergic and non-serotonergic neuronal binding sites examined. When examined for its ability to inhibit forskolin-induced cyclic AMP accumulation in cells stably transfected with human 5-HT1F receptors, LY344864 was shown to be a full agonist producing an effect similar in magnitude to serotonin itself. After an intravenous dose of 1 mg/kg, rat plasma LY344864 levels declined with time whereas brain cortex levels remained relatively constant for the first 6 hours after injection. Oral and intravenous LY344864 administration potently inhibited dural protein extravasation caused by electrical stimulation of the trigeminal ganglion in rats. Taken together, these data demonstrate that LY344864 is a selective 5-HT1F receptor agonist that can be used to explore both the in vitro and in vivo functions of this receptor.

Animals↗
PubMed1997

Recollective and automatic uses of memory.

Three cued-recall experiments examined the effects of learning conditions and set size on recollective and automatic uses of memory. Words were studied under different conditions and had either small or large preexisting associative sets. Results based on the process-dissociation procedure showed that learning conditions and set size influenced recollective uses of memory, whereas only set size influenced automatic uses. Other results indicated that process-dissociation and direct-indirect test procedures produce similar results. The findings suggest that the relative contributions of recently acquired information and preexisting information depend on how memory is being used. Recollective uses of memory are affected by the nature of recent study and by what such study activates in long-term memory. In contrast, automatic uses of memory are more affected by what the test cue automatically activates than by what has been learned during recent study.

Automatism↗
PubMed1997

X-linked situs abnormalities result from mutations in ZIC3.

Vertebrates position unpaired organs of the chest and abdomen asymmetrically along the left-right (LR) body axis. Each structure comes to lie non-randomly with respect to the midline in an overall position designated situs solitus, exemplified in humans by placement of the heart, stomach and spleen consistently to the left. Aberrant LR axis development can lead to randomization of individual organ position (situs ambiguus) or to mirror-image reversal of all lateralized structures (situs inversus). Previously we mapped a locus for situs abnormalities in humans, HTX1, to Xq26.2 by linkage analysis in a single family (LR1) and by detection of a deletion in an unrelated situs ambiguus male (Family LR2; refs 2,3). From this chromosomal region we have positionally cloned ZIC3, a gene encoding a putative zinc-finger transcription factor. One frameshift, two missense and two nonsense mutations have been identified in familial and sporadic situs ambiguus. The frameshift allele is also associated with situs inversus among some heterozygous females, suggesting that ZIC3 functions in the earliest stages of LR-axis formation. ZIC3, which has not been previously implicated in vertebrate LR-axis development, is the first gene unequivocally associated with human situs abnormalities.

Amino Acid Sequence↗
PubMed1997

Atypical glandular cells of undetermined significance. Diagnostic accuracy and interobserver variability using select cytologic criteria.

Histologic follow-up of patients with the Bethesda system cervical-vaginal diagnosis of atypical glandular cells of undetermined significance (AGUS), "favor endocervical origin", or "not otherwise specified" (NOS) shows a high percentage of clinically significant (neoplastic or preneoplastic) lesions. Using the criteria of atypical single cells, irregular nuclear membranes, and decreased cytoplasm, eight observers retrospectively reclassified 88 AGUS, "favor endocervical", or NOS smears using a probabilistic scheme. Follow-up showed 46 clinically significant and 42 benign lesions. The mean accuracy for all observers and the experienced observers was 65% and 72%, respectively. For the experienced observers, the mean specificity of a "favor clinically significant" category was 72%; the mean sensitivity of a "favor benign" category was 90%. For the less experienced observers, subclassification had poor predictive value. We conclude that experienced observers may use specific criteria to correctly subclassify AGUS lesions, and this may aid in patient management.

Female↗
PubMed1997

Molecular and phenotypic variation in patients with severe Hunter syndrome.

Severe Hunter syndrome is a fatal X-linked lysosomal storage disorder caused by iduronate-2-sulphatase (IDS) deficiency. Patients with complete deletion of the IDS locus often have atypical phenotypes including ptosis, obstructive sleep apnoea, and the occurrence of seizures. We have used genomic DNA sequencing to identify several new genes in the IDS region. DNA deletion patients with atypical symptoms have been analysed to determine whether these atypical symptoms could be due to involvement of these other loci. The occurrence of seizures in two individuals correlated with a deletion extending proximal of IDS, up to and including part of the FMR2 locus. Other (non-seizure) symptoms were associated with distal deletions. In addition, a group of patients with no variant symptoms, and a characteristic rearrangement involving a recombination between the IDS gene and an adjacent IDS pseudogene (IDS psi), showed normal expression of loci distal to IDS. Together, these results identify FMR2 as a candidate gene for seizures, when mutated along with IDS.

Chromosome Mapping↗
PubMed1997

Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity.

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric-directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non-homologous interchromosomal exchange.

Adrenoleukodystrophy↗
PubMed1997

One step is not enough: making better use of association norms to predict cued recall.

Cued recall is strongly affected by the strength of the preexisting connection between the test cue and the information to be recalled, the target. In all past work, preexisting cue-to-target strength has been measured by the probability that the cue produced the target in free association. This paper presents four experiments showing that this use of such norms underestimates the strength of the connection and that a more accurate estimate can be obtained by incorporating indirect as well as direct connections in the estimate. Experiments 1 and 2 showed that in extralist cued recall both the strength and number of two-step indirect connections facilitate recall. Experiment 3 showed that three-step connections have negligible effects. Experiment 4 used an intralist task in which cue and target are first studied together, and the results showed once again that indirect connections can affect recall. In all of these experiments, indirect connections had an effect on recall that was larger when direct cue-to-target strength was weak than when it was strong. Implications for using association norms in research are described, and an algorithm for using association norms to measure cue-to-target strength is proposed.

Adult↗
PubMed1997

Why the profession of occupational therapy will flourish in the 21st century. The 1996 Eleanor Clarke Slagle Lecture.

The use of occupation as a therapeutic method is the essence of the profession of occupational therapy. This core of therapeutic occupation is flexible across cultures, times, health care environments, and different philosophies of the nature of the human being. Given this adaptability, the profession espouses diverse models of practice--the multiple frames of reference that guide therapeutic occupation for different populations in different settings. Across the history of the profession, therapeutic occupation has been the common core of otherwise different approaches to intervention. Although each of the many past and current models of practice has a different viewpoint, the common factor is the synthesis of occupational forms designed to elicit meaningful and purposeful occupational performance. Occupational synthesis is the essential act of the occupational therapist. It is necessary that occupational therapists confirm the power of therapeutic occupation through research that examines the profession's central principles. Occupational therapists are also urged to use the term occupation consistently and proudly in their interactions with recipients of therapy, fellow health care professionals, and each other. The profession of occupational therapy will flourish because occupation, its core, is so basic to human health yet so flexible, depending on the needs of the individual human being.

Activities of Daily Living↗
PubMed1997

Predisposition to the fragile X syndrome in Jews of Tunisian descent is due to the absence of AGG interruptions on a rare Mediterranean haplotype.

We have studied the ethnic distribution of the fragile X syndrome in Israel and have found that 36/136 (26.5%) of apparently unrelated pedigrees were of Tunisian Jewish descent. The Tunisian Jews, however, constitute only 2%-3% of the general Israeli population, identifying the first ethnic group significantly (P < .001) predisposed to the development of this disease. Associated with this increase in disease prevalence, we have found an unusually high incidence of FMR1 CGG repeats devoid of AGG interruptions among the normal Tunisian Jewish population (30/150, or 20.0%). Furthermore, the proportion of these alleles beyond the FMR1 CGG repeat instability threshold (>35 repeats) (8/150, or 5.3%) was significantly greater (P < .04) than that proportion found among non-Tunisian Jewish controls in Israel (1/136). Haplotype analysis has indicated that these large uninterrupted CGG repeat alleles are present on a previously unreported (DXS548-FRAXAC1-FRAXAC2) haplotype that accounts for all observed cases of disease among Tunisian Jewish X chromosomes. The high prevalence of disease among Tunisian Jews, we suggest, is due to a founder effect of this rare haplotype, which is completely devoid of AGG interruptions in the Jewish population of Tunisia.

Arabs↗
PubMed1997

The importance of the physical examination.

Although the presentation of a patient with wrist complaints is a common occurrence for many hand surgeons, the diagnosis may not be arrived at very easily or quickly. The physical examination is therefore of chief importance as our knowledge of the wrist and wrist surgery continues to increase.

Humans↗