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Biomedical subjects

A Peterson

Publications and source records attributed to A Peterson.

At least 73 records · Page 4Linked to original sources
PubMed1992

Intragenic regulatory elements contribute to transcriptional control of the neurofilament light gene.

To date, no DNA regions involved in the neuron-specific expression of the neurofilament light gene (NF-L) have been defined using transfection assays in cultured cells. To identify those regulatory regions in the human NF-L gene, we generated transgenic mice with a construct containing the basal NF-L promoter (-292 to +15) fused to the cat gene and with three DNA fragments of 21.5, 7.6 and 4.9 kb each, including NF-L with different lengths of either 5'- or 3'-flanking sequences. We show that the proximal NF-L 5' region (0.3 kb) constitutes a weak promoter and that it lacks information to confer neural specificity. However, appropriate expression in the nervous system occurred when this minimal promoter was combined with either 7.3 or 4.6 kb of NF-L sequences downstream from the transcription start point. We conclude that the intragenic NF-L region contains cis-acting elements conferring cell-type-specific regulation on the basal activity of the NF-L promoter. Interestingly, AP-2 motifs were found within homologously placed introns of all three NF genes, as well as in the promoter regulatory regions of many neuronal genes. We propose that the acquisition of introns by an ancestral intronless IF gene may have contributed to the emergence of a lineage of IF genes expressed in the nervous system.

Animals↗
PubMed1992

Auditory event-related potentials in HIV-1 infection: a study in the drug-user risk group.

Features of event-related potentials (ERPs) may be sensitive and clinically useful markers of central nervous system infection by the human immunodeficiency virus (HIV-1); however, this application has not been studied in the risk group of intravenous drug users. Auditory ERPs generated by an "oddball" paradigm were analyzed for 39 male drug abusers as part of a multimodal assessment. Stage of HIV-1 infection was associated with prolongations of P1, N1, and P3 components of the ERP waveform. Only patients with full acquired immunodeficiency syndrome showed statistically significant increases in waveform prolongations. Specific neuropsychological deficits were not related to waveform latency prolongations.

AIDS Dementia Complex↗
PubMed1991

A genetic approach for analyzing the pathway of LamB assembly into the outer membrane of Escherichia coli.

Results presented in this study demonstrate that a mutation which inserts an additional tyrosine between the 2 tyrosines at residues 118 and 119 of mature LamB protein results in a temperature-dependent assembly defect. This defect leads to the accumulation of an intermediate at the restrictive temperature that is most likely an assembly-defective monomer. These monomers are rapidly degraded in the wild type (htrA+) strain, and the biphasic kinetics of this degradation indicate that the mutation affects the assembly process and not the final product, i.e. stable trimers. In addition, our data show that the temperature-dependent assembly defect in the mutant strain is reversible, and therefore the accumulated monomers represent a true assembly intermediate. Fractionation studies show that the monomers, which can be accumulated in htrA (degP) mutants at the restrictive temperature, are associated with the outer membrane, indicating that trimerization of LamB is not a prerequisite for localization.

ATP-Binding Cassette Transporters↗
PubMed1991

Neuroleptics improve sustained attention in schizophrenia. A study using signal detection theory.

To test the hypothesis that antipsychotic drugs improve attentional processes in schizophrenia, we used a computer-controlled, perceptually degraded continuous performance test (CPT), based on signal detection theory. CPT stimuli were degraded (blurred) to reduce discriminability so that signal detection analysis could be used to distinguish specific attentional processes, as measured by A', from nonspecific factors, as measured by B". Thirteen medicated and 12 neuroleptic-withdrawn schizophrenics visually monitored digits to detect a target under perceptually undegraded and degraded conditions. The principal result was that the neuroleptic-withdrawn patients showed a significant decline in the attention-specific measure of A' over time on task only for the degraded targets, independent of changes in the nonspecific index of B". These results demonstrate that neuroleptic withdrawal may compromise specific attentional processes, namely the ability to sustain attention, as measured by a precise performance task which controlled for nonspecific factors.

Adult↗
PubMed1990

Diffuse kinetochores and holokinetic anaphase chromatin movement during mitosis in the hemipteran Agallia constricta (leafhopper) cell line AC-20.

Mitosis in the hemipteran Agallia constricta (leafhopper) cell line AC-20 was examined by light microscopy of living and fixed cells. During early prometaphase the numerous small (0.30-3.0-microns) chromosomes appear as discrete units that lack a primary constriction. However, by late prometaphase the chromosomes are tightly packed at the spindle equator and are no longer clearly resolvable as individuals. When viewed from the side the metaphase chromatin appears as a 2-3-microns wide band that spans the width of the spindle; when viewed from the pole it appears as a fenestrated disk. The metaphase chromatin splits at anaphase into two sister chromatin plates, each of which exhibits holokinetic poleward movement, i.e., all parts of each plate move as a single unit with the same velocity. In many early-to-mild anaphase cells the separating sister plates are connected by chromatin-containing bridges that break as anaphase progresses. Ultrastructural analyses of serial thick and thin sections from cells fixed by conventional, OsO4/KFeCN, or high pressure rapid freezing methods, reveal that by metaphase all of the chromosomes are interconnected to form a large, irregularly shaped fenestrated disk of chromatin. Similar analyses reveal that adjacent chromatids remain interconnected throughout anaphase. Each disk of metaphase and anaphase chromatin contains numerous kinetochores recessed within its pole-facing surface. Kinetochores consist of a fine, faintly staining fibrillar material arranged along the chromatin surface as thin (0.1-0.3 micron dia.) rods varying considerably (0.15-2.3 microns) in length. From these observations we conclude that the polycentric metaphase chromatin of A. constricta, and its holokinetic behavior during anaphase, arises from the aggregation or cohesion of smaller prometaphase chromosomes, each of which contains a single, diffuse kinetochore.

Anaphase↗
PubMed1990

Mouse chimeras and genetic rescue of mosaic muscle.

The nuclear-cytoplasmic relationships existing within mosaic muscle will likely determine whether myoblast transfer can effectively rescue diseased muscle. The mouse chimera preparation is one source of such mosaic muscle in which that in vivo relationship can be investigated in the complete absence of complicating immunological or surgical trauma. For several metabolic enzymes, the mature muscle fiber appears to contain a homogeneous mix of the proteins encoded by multiple myonuclei. This relationship is clearly not representative of all muscle proteins, as several examples of proteins highly localized to "nuclear territories" have now been described. Nonetheless, the intrafiber distribution of certain enzymes, particularly GP1-1, is appropriate for the basis of a genotype marking system applicable to mosaic fibers. In vitro rescue of mdg myotubes is readily achievable by incorporation of few normal myonuclei and possibly by only one. In vivo requirements are apparently far more stringent and an hypothesis in which the mdg gene product, a Ca+(+) channel subunit, is restricted to nuclear territories would be consistent with the disparate results obtained in vitro and in vivo. Finally, chimeras containing mdx/mdx cells may show a partial amelioration of muscle pathology and may provide a means of determining the minimum genetically normal myonuclear compliment required to prevent degeneration of dystrophin-deficient fibers.

Animals↗
PubMed1990

Neurofilament gene expression in transgenic mice.

1. DNA fragments that include the human neurofilament NF-L gene was found to be correctly expressed in the majority of neurons in transgenic mice. 2. The NF-L transgene product, which is detectable in situ with a species-specific monoclonal antibody, provides a powerful genotype marking system applicable to developmental and regeneration studies of the mammalian nervous system. 3. The proximal 5'-flanking region of the NF-L gene is sufficient to direct expression of a heterologous gene in the mouse nervous system.

Animals↗
PubMed1989

Cellular mosaicism in the methylation and expression of hemizygous loci in the mouse.

Proposed models for the inheritance of locus-specific methylation phenotypes in somatic cells include those in which there is stable inheritance of a methylation pattern such that all cells contain a similarly methylated locus, as well as models in which the inheritance of methylation can be variable. We investigated these possibilities by examining the methylation and expression of hemizygous loci in the mouse. Our results demonstrate that differences in both methylation and expression can exist between apparently identical cells and that such mosaicism is genetically controlled.

Animals↗
PubMed1989

A combined in ovo-in vitro system for studies of volatile compounds on brain development: differential effects of carbon tetrachloride on neurones and astrocytes.

A method for studies of organic solvent effects on the development of neurones and astrocytes is described. Chick embryos in ovo were exposed to a low concentration of carbon tetrachloride vapours. After the exposure, primary cultures of neurones and astrocytes were prepared from the brain hemispheres of the embryos. Toxic effects of the solvent were analyzed in the cultures during the course of cellular differentiation as changes in cell growth and morphology, respiratory activity, and biochemical properties characteristic of each cell type. The development of neurones from embryos exposed from day 5 to day 8 to 25 p.p.m. of carbon tetrachloride was not affected by the exposure. On the other hand, growth rate and respiratory activity of astrocytes from embryos exposed from day 11 to day 14 to 25 p.p.m. of CCl4 were affected by the exposure, whereas no morphological changes or changes in the cyclic AMP levels could be observed. Consequently, low concentrations of carbon tetrachloride seem to affect the development of astrocytes rather than that of neurones in our experimental system.

Animals↗
PubMed1989

Epigenetic and genetic factors affect transgene methylation imprinting.

In some lines of transgenic mice, the methylation of MspI sites within or adjacent to the transgene locus is affected by the sex of the parent from which the transgene is inherited. These differences are consistent with a role for DNA methylation in genome imprinting. In a previous report, we noted that in one such line, all offspring of females exhibited hypermethylation of the transgene while only some offspring of males carried a hypomethylated transgene. In this report, we provide evidence that this phenomenon is controlled by at least two factors, one of which acts in cis and is dependent on the transgene locus, and one of which acts in trans and is supplied by the maternal genome. We also provide evidence that there are genetic differences between inbred mouse strains in the trans-acting factor.

Animals↗
PubMed1988

A transgene containing lacZ inserted into the dystonia locus is expressed in neural tube.

The site of integration of transgenes in the host genome can affect levels of expression and occasionally confer ectopic patterns of expression on otherwise tissue-specific genes. We describe here a line of mice in which an hsp68-lacZ transgene is expressed in unstressed developing neural tissue and where the transgene insertion has caused a mutation of a neural tissue-specific gene, dystonia musculorum (dt). This coincidence suggests that expression of the hsp68-lacZ construct may be controlled directly by cis-acting regulatory sequences that normally control the developmental expression of the dt gene. Such constructs may serve as useful tools for identifying new tissue-specific enhancers and their associated genes.

Animals↗
PubMed1988

Synergistic T cell activation via the physiological ligands for CD2 and the T cell receptor.

T cells may be activated either by the antigen-specific T cell receptor (TCR)-CD3 complex or the cell surface receptor CD2. A natural ligand for CD2 has been found to be lymphocyte function-associated antigen 3 (LFA-3), a widely distributed cell surface glycoprotein. To investigate the interaction of these two pathways, we have expressed the cDNA encoding the human CD2 molecule in a murine T cell hybridoma that produces IL-2 in response to HLA-DR antigens. Expression of the CD2 molecule markedly enhances IL-2 production in response to LFA-3+ antigen-bearing stimulator cells, and this stimulation is inhibited by anti-CD2 and anti-LFA-3 mAb. To further define the role of LFA-3 in antigen-dependent T cell activation, we have studied the ability of the purified ligands of CD2 and the TCR to stimulate the hybridoma. Neither liposomes containing purified HLA-DR antigens nor liposomes containing purified LFA-3 were able to stimulate the parent or the CD2+ hybridoma. However, liposomes containing both purified LFA-3 and HLA-DR, the physiological ligands for CD2 and the TCR, respectively, stimulate IL-2 production by the CD2+ but not the parent hybridoma, suggesting that complementary interactions between the TCR-CD3 complex and the CD2 pathway may regulate lymphocyte activation. To determine whether the CD2/LFA-3 interaction participates in cell-cell adhesion and provides an activation signal, we have constructed a cytoplasmic deletion mutant of CD2, CD2 delta B, in which the COOH-terminal 100 amino acids of CD2 have been replaced with a serine. Hybridomas expressing the CD2 delta B molecule were examined. Deletion of the cytoplasmic domain of CD2 did not alter binding of LFA-3 but eliminated the ability of CD2 to increase the response of the hybridoma to liposomes containing both HLA-DR and LFA-3, demonstrating that adhesion of LFA-3 to CD2 alone was insufficient for activation, and that the cytoplasmic domain was required for LFA-3 stimulation through the CD2 molecule. T cells may be activated by purified LFA-3 binding to CD2 and the TCR interacting with its ligand, and these signals appear to be synergistic for the T cell. These results suggest that the CD2/LFA-3 interaction not only plays a role in cell-cell adhesion but provides a stimulatory signal for T cell activation.

Amino Acid Sequence↗
PubMed1988

Genetic analysis of monoclonal antibody and HIV binding sites on the human lymphocyte antigen CD4.

Saturation mutagenesis and a complement fixation selection have yielded CD4 point mutants with impaired antibody and human immunodeficiency virus binding. The patterns of amino acid substitution, in conjunction with previous antibody cross-blocking data, affirm the similar tertiary structures of the CD4 amino-terminal domain and immunoglobulin variable regions. Single residue substitutions affecting virus binding and syncytium formation are observed over an eight residue segment located in a portion of the molecule homologous to the second hypervariable region of an antibody combining site.

Amino Acid Sequence↗
PubMed1988

Functional analysis of a cytoplasmic domain-deleted mutant of the CD4 molecule.

The CD4 molecule is a receptor found on a subset of T lymphocytes. It has been proposed that, upon binding MHC class II molecules expressed on APC, the CD4 molecule enhances the responsiveness of the T cell by increasing intercellular avidity and/or by transducing an intracellular signal. We have analyzed the effect of removing the cytoplasmic domain of the CD4 molecule on the ability of the CD4 molecule to enhance T cell responsiveness. The cytoplasmic domain-deleted mutant of the CD4 molecule (CD4 delta) was found to be as efficient as the CD4 molecule at enhancing responsiveness to cells bearing the appropriate Ag. If subcellular Ag in the form of purified Ag incorporated into liposomes was used, the CD4 molecule was found to be much more efficient than the CD4 delta molecule at enhancing responsiveness. However, the defect in the ability of the CD4 delta molecule to enhance responsiveness could be compensated for by increasing the level of expression of the CD4 delta molecule.

Amino Acid Sequence↗
PubMed1988

Immunohistochemical identification of quinolinic acid phosphoribosyltransferase in glial cultures from rat brain.

Glial cell cultures were shown to contain 3 identifiable classes of cells which could be specifically stained with antibodies directed against quinolinic acid phosphoribosyltransferase (QPRT), the catabolic enzyme of the endogenous excitotoxin quinolinic acid. Some, but not all, QPRT-positive cells also contained glial fibrillary acidic protein. These cultures may constitute an in vitro system in which cerebral quinolinic acid metabolism and function can be examined.

Animals↗