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Biomedical subjects

C A Nelson

Publications and source records attributed to C A Nelson.

At least 19 recordsLinked to original sources
PubMed1992

Identification of the naturally processed form of hen egg white lysozyme bound to the murine major histocompatibility complex class II molecule I-Ak.

A murine B-cell lymphoma bearing the class II major histocompatibility complex molecule I-Ak was cultured with the protein antigen hen egg white lysozyme (HEL). The I-Ak molecules were purified, and their associated peptides were extracted for characterization. Five HEL peptides were identified. Four contained the 10 amino acid residues HEL 52-61 (DYGILQINSR) but were heterogeneous in length and flanking residues. This core sequence is known to confer a high binding affinity for I-Ak. One additional peptide contained the amino acid residues HEL 48-60. These data demonstrate that the HEL epitope containing residues 52-61 is the most abundant HEL epitope presented on the major histocompatibility complex of the antigen-presenting cells and consequently explains its immunodominance.

Amino Acid Sequence↗
PubMed1992

A negative retinoic acid response element in the rat oxytocin promoter restricts transcriptional stimulation by heterologous transactivation domains.

Retinoic acid receptors are ligand-dependent transcription factors that stimulate gene transcription from promoters containing retinoic acid or thyroid hormone response elements. We describe a high-affinity binding site from the rat oxytocin promoter that mediates negative transcriptional regulation by the retinoic acid receptor. To examine whether strong, constitutive transactivation domains would be capable of stimulating gene transcription when bound to this DNA binding site that normally mediates transcriptional repression, we fused the transactivation domain of the herpes simplex viral protein VP16 to the amino terminus of the retinoic acid receptor and tested the activity of the chimeric protein on the negative retinoic acid response element. This chimeric retinoic acid receptor acted as a strong, constitutive transactivator when bound to promoters containing palindromic thyroid hormone/retinoic acid response elements but surprisingly it still repressed gene transcription when bound to promoters containing the oxytocin-negative retinoic acid response element. These results suggest that a negative DNA binding site itself can inhibit the function of even potent constitutive transactivation domains, and provide evidence that tethering of a constitutive transactivation domain to DNA is insufficient to activate gene transcription.

Animals↗
PubMed1992

Neural and behavioral correlates of emotion recognition in children and adults.

Event-related potentials (ERPs), accuracy scores, and reaction times were used to examine the recognition of emotional expressions. Adults and 7-year-old children saw upright and inverted chromatic slides of the facial expressions of happiness, fear, surprise, and anger, and were asked to press a button for either "happy" or "angry" faces. A positive-going waveform (P300) was apparent at parietal scalp (Pz) and at left and right temporal scalp. Although the behavioral data were similar for both children and adults (e.g., both had more difficulty recognizing angry expressions than happy ones, and angry expressions were more difficult to recognize upside-down than were happy faces), the ERPs indicated that children responded differently than adults did to happy and angry expressions. Adults showed greater P300 amplitude to happy faces, while children showed greater P300 amplitude to angry faces. In addition, for adults, but not children, there were greater P300 amplitude responses at right vs. left temporal scalp.

Adult↗
PubMed1992

Neural and behavioral correlates of visual recognition memory in 4- and 8-month-old infants.

The neural and behavioral correlates of the 4- and 8-month-old infant's ability to distinguish between frequently and infrequently presented familiar and novel events was examined. Cortical event-related potentials (ERPs) were recorded as infants were familiarized to two faces. During the test trials that followed, one of these faces was presented frequently, and the other infrequently; on each of the remaining 20% of the trials, a previously unseen, novel face was presented. Following the ERP phase, infants' looking times were recorded to pairs of faces, some of which had been seen during the ERP testing, and some of which had not. At 4 months the ERP activity invoked by the three classes of events was similar, suggesting that infants were unable to distinguish among them. At 8 months the ERP activity differed only between the Infrequent Novel events and the two classes of familiar events, but did not differ between the frequently and infrequently presented familiar events. The ERP findings complement previously reported data from 6-month-old infants in describing a trend whereby infants become increasingly able to respond to stimuli on the basis of whether they have been seen before, and not on the basis of how often they had been seen. The behavioral data at both 4 and 8 months were less clear cut than the ERP data. These findings are discussed in the context of the neural and cognitive processes involved in dissociating probability information from novelty detection.

Age Factors↗
PubMed1991

Calcium/calmodulin-dependent protein kinase mediates a pathway for transcriptional regulation.

Calcium influx in response to extracellular signals can modulate gene transcription. A constitutive, calcium/calmodulin-independent mutant of type II calcium/calmodulin-dependent protein kinase was capable of increasing the transcription rate of specific genes independently of protein kinase C activation. This increase was mediated by transferable cis-active elements capable of binding the transcription factor CAAT/enhancer binding protein. Therefore, the activation of type II calcium/calmodulin-dependent protein kinase in response to stimuli that increase intracellular calcium is proposed to represent a distinct second messenger pathway in calcium-mediated regulation of gene transcription.

Animals↗
PubMed1991

P300 brain activity in seizure patients preceding temporal lobectomy.

Event-related potentials were recorded over occipital and parietal scalp from 20 patients suffering from intractable partial complex seizures prior to undergoing a temporal lobectomy. Subjects were presented with language and nonlanguage visual stimuli using a divided-field, "odd-ball" paradigm. Although behavioral performance (button-press accuracy, reaction time, and running counts) was comparable across all groups (although accuracy was worse for those in the left temporal group), patients showed tremendous variability in both the amplitude and latency of the P300 response. Particularly notable was the observation that more slow wave activity was present among the patients than among the control subjects, and those scheduled for a left temporal resection evinced more amplitude reduction than those scheduled for a right temporal resection. In addition, a number of patients appeared not to show a P300 response at all. These results are discussed in the context of the utility of using noninvasive event-related potential measures to examine both memory impairment and the integrity of the neural structures that mediate memory functioning in certain patient populations.

Adult↗
PubMed1990

Evidence for CD8-independent T cell maturation in transgenic mice.

Double-negative (CD4-/CD8-) T cells expressing the alpha/beta transgenic TCR from the 2C cell line (anti-H-2Ld) were examined in the periphery of animals whose MHC type produces positive, negative, or no selection for differentiation of the TCR on single positive (CD8+) cells. Regardless of the selection haplotype the CD4-/CD8- cells are capable of activation by anticlonotypic mAb indicating that negative selection does not inactivate the "forbidden" TCR. Rather, the lack of response to H-2Ld in the negative haplotype is likely to absence of CD8 required to produce a functional response to H-2Ld. The similarity of surface phenotype and functional activity of these CD4-/CD8- cells maturing in different haplotypes suggests they may arise by an alternative lineage which, unlike the dominant TCR alpha/beta pathway, does not require coexpression of CD4/CD8.

Animals↗
PubMed1990

The lateralization of language comprehension using event-related potentials.

Event-Related Potentials were recorded over occipital and parietal scalp from left- and right-handed adults presented with a language and a non-language visual stimulus using a divided field, "oddball" paradigm. The major finding of interest was that the P300 component was larger over the left than the right hemisphere of the right-handers when the language stimulus was presented to the left hemisphere; there were no hemispheric differences for the left-handers, regardless of field of presentation. These results are discussed in the context of developing noninvasive measures to lateralize language function.

Arousal↗
PubMed1990

Positive selection of transgenic receptor-bearing thymocytes by Kb antigen is altered by Kb mutations that involve peptide binding.

A specific interaction between the class I major histocompatibility complex molecule Kb and thymocytes expressing the antigen receptor from the cytolytic T lymphocyte 2C enhances maturation of T cells of the CD8 lineage in transgenic mice. By analyzing transgenic mice backcrossed to Kbm mutant strains of mice, we have identified five bm mutations of the Kb antigen-encoding gene that alter the positive selection of thymocytes induced by Kb antigen. Compared with Kb, Kbm10 and Kbm1 did not induce significant maturation of 2C T-cell receptor-bearing thymocytes, and Kbm8 antigen positively selected for transgenic thymocytes only weakly. Altering residue 77 of Kb molecule from aspartic acid to serine made Kbm3 and Kbm11 allogeneic targets for the 2C antigen receptor and caused deletion of transgenic thymocytes. This deletion spared T cells that expressed low levels of CD8, a result differing from the total deletion of CD8-bearing T cells seen in mice that expressed the original target alloantigen Ld. This evidence indicates that (i) self-peptides bound to thymic major histocompatibility complex molecules can influence the positive selection of thymocytes and (ii) thymocytes with apparently weak interaction with self-major histocompatibility complex antigens can escape clonal deletion.

Animals↗
PubMed1990

The C'-terminal interaction domain of the thyroid hormone receptor confers the ability of the DNA site to dictate positive or negative transcriptional activity.

To investigate mechanisms responsible for positive and negative transcriptional control, we have utilized two types of promoters that are differentially regulated by thyroid hormone (T3) receptors. Promoters containing the palindromic T3 response element TCAGGTCA TGACCTGA are positively regulated by the T3 receptor after the administration of T3, whereas otherwise identical promoters containing the estrogen response element TCAGGTCA CTG TGACCTGA can be regulated negatively; converse effects are observed with the estrogen receptor. We describe evidence that the transcriptional inhibitory effects of the T3 or estrogen receptors on the estrogen or T3 response elements, respectively, are imposed by amino acid sequences in the C'-terminal region that colocalize with dimerization and hormone-binding domains and that these sequences can transfer inhibitory functions to other classes of transcription factors. Removal of the C'-terminal dimerization and hormone-binding domains of either the alpha T3 or estrogen receptors permits each receptor to act constitutively to enhance transcription on both T3 and estrogen response elements. It is, therefore, suggested that protein-protein interactions between receptor C' termini limit the subset of DNA binding sites on which transcriptional activation occurs.

Animals↗
PubMed1990

Event-related potentials to emotional and neutral stimuli.

The present study examined subjects' cognitive processing of pictures of emotional and neutral facial expressions, as measured by Event-Related Potentials (ERPs). In Experiment 1, 10 subjects viewed two slides of a woman modelling angry and happy expressions; in Experiment 2, 10 subjects viewed slides of two women modelling neutral expressions. One face appeared on 20% of the trials and the other on 80% of the trials. Subjects counted the low frequency target face. In both experiments, the area of the P300 component was larger at Pz than Cz. In Experiment 1, P300 area was larger when the target was happy; peak amplitude was greater when the target was angry. No differences between neutral target faces were found for P300 amplitude or area in Experiment 2. These results suggest that emotional versus neutral facial expressions elicit different electrophysiological responses; responses are further differentiated to positive versus negative expressions.

Adult↗
PubMed1990

Functional analysis of the murine T-cell receptor beta enhancer and characteristics of its DNA-binding proteins.

The minimal T-cell receptor (TCR) beta-chain (TCR beta) enhancer has been identified by transfection into lymphoid cells. The minimal enhancer was active in T cells and in some B-lineage cells. When a larger fragment containing the minimal enhancer was used, its activity was apparent only in T cells. Studies with phytohemagglutinin and 4 beta-phorbol-12,13-dibutyrate revealed that the enhancer activity was increased by these agents. By a combination of DNase I footprinting, gel mobility shift assay, and methylation interference analysis, seven different motifs were identified within the minimal enhancer. Furthermore, competition experiments showed that some of these elements bound identical or similar factors that are known to bind to the TCR V beta promoter decamer or to the immunoglobulin enhancer kappa E2 or muEBP-E motif. These shared motifs may be important in the differential gene activity among the different lymphoid subsets.

Animals↗
PubMed1989

Identification and characterization of new murine T cell receptor beta chain variable region (V beta) genes.

By screening previously isolated genomic clones spanning the mouse TCR V beta locus with V beta-specific oligonucleotides, we have isolated one new functional V beta gene and six V beta pseudogenes. Because this method of identifying new genes does not depend on expression levels, we conclude that most, if not all, V beta genes in the mouse have been identified. The newly identified pseudogenes increase the frequency of mouse TCR V beta pseudogenes to 28%, a frequency similar to that estimated for mouse Ig VH pseudogenes (24). Three of the newly discovered pseudogenes are clustered in a region around another pseudogene (V beta 17b). The extensive DNA diversity, as reflected in both the nucleotide sequence and the RFLP, indicates that this genomic region is a possible hotspot of recombination. The new functional gene, V beta 19a, is expressed at very low levels, which explains why it has not been isolated earlier. V beta 19 shows expression patterns that correlate with the previously described Va beta and Vb beta haplotypes.

Amino Acid Sequence↗
PubMed1989

An extremely polymorphic locus on the short arm of the human X chromosome with homology to the long arm of the Y chromosome.

A genomic DNA clone named CRI-S232 reveals an array of highly polymorphic restriction fragments on the X chromosome as well as a set of non-polymorphic fragments on the Y chromosome. Every individual has multiple bands, highly variable in length, in every restriction enzyme digest tested. One set of bands is found in all males, and co-segregates with the Y chromosome in families. These sequences have been regionally localized by deletion mapping to the long arm of the Y chromosome. Segregation analysis in families shows that all of the remaining fragments co-segregate as a single locus on the X chromosome, each haplotype consisting of three or more polymorphic fragments. This locus (designated DXS278) is linked to several markers on Xp, the closest being dic56 (DXS143) at a distance of 2 cM. Although it is outside the pseudoautosomal region, the S232 X chromosome locus shows linkage to pseudoautosomal markers in female meiosis. In determining the X chromosome S232 haplotypes of 138 offspring among 19 families, we observed three non-parental haplotypes. Two were recombinant haplotypes, consistent with a cross-over among the S232-hybridizing fragments in maternal meiosis. The third was a mutant haplotype arising on a paternal X chromosome. The locus identified by CRI-S232 may therefore be a recombination and mutation hotspot.

Cell Line↗
PubMed1989

Past, current, and future trends in infant face perception research.

Our review of infant face perception research had three purposes. First, we briefly attempted to describe a number of themes prevalent in the literature before 1979. Although the themes were broad and difficult to identify clearly, the underlying issues of the time seemed to fit three headings: (a) research that either did or did not support the existence of an innate preference for faces, (b) research that explored infants' general knowledge of faces, particularly their sensitivity to the invariant properties of faces, and (c) how infants acquire information about faces, as demonstrated through studies of facial scanning and feature discrimination. Our second goal was to summarize current trends. Here emphasis was placed on studies concerned with the face as a conveyer of socially-salient information, the neurological basis of face perception, and recent methodological innovations. Our final goal was to provide a sampling of issues and questions that seemed appropriate for investigation during the next decade.

Attention↗
PubMed1988

Positive and negative selection of an antigen receptor on T cells in transgenic mice.

The T-cell repertoire found in the periphery is thought to be shaped by two developmental events in the thymus that involve the antigen receptors of T lymphocytes. First, interactions between T cells and major histocompatibility complex (MHC) molecules select a T-cell repertoire skewed towards recognition of antigens in the context of self-MHC molecules. In addition, T cells that react strongly to self-MHC molecules are eliminated by a process called self-tolerance. We have recently described transgenic mice expressing the alpha beta T-cell receptor from the cytotoxic T lymphocyte 2C (ref. 11). The clone 2C was derived from a BALB.B (H-2b) anti-BALB/c (H-2d) mixed lymphocyte culture and is specific for the Ld class I MHC antigen. In transgenic H-2b mice, a large fraction of T cells in the periphery expressed the 2C T-cell receptor. These T cells were predominantly CD4-CD8+ and were able to specifically lyse target cells bearing Ld. We now report that in the periphery of transgenic mice expressing Ld, functional T cells bearing the 2C T-cell receptor were deleted. This elimination of autoreactive T cells appears to take place at or before the CD4+CD8+ stage in thymocyte development. In addition, we report that in H-2s mice, a non-autoreactive target haplotype, large numbers of CD8+ T cells bearing the 2C T-cell receptor were not found, providing strong evidence for the positive selection of the 2C T-cell receptor specificity by H-2b molecules.

Animals↗