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K A Moore

Publications and source records attributed to K A Moore.

At least 109 records · Page 6Linked to original sources
PubMed1991

Kindling-induced potentiation in the piriform cortex.

At intensities sufficient to induce epileptiform afterdischarges, repeated electrical stimulation of limbic structures can lead to the development of permanent increases in the strength of the epileptiform response (kindling). Field potentials evoked by pulse stimulation are also increased in amplitude in a number of forebrain pathways following kindling. This kindling-induced potentiation effect is similar in many respects to the 'long-term potentiation' (LTP) effect which is produced by non-epileptogenic stimulation. There are, however, some interesting differences. For example, kindling-induced potentiation can far outlast LTP. In these experiments, we attempted to determine the longevity of the kindling-induced potentiation of the response evoked in the piriform cortex by olfactory bulb stimulation, following olfactory bulb kindling. This system was targeted because both the olfactory bulb and the piriform cortex are highly reactive kindling sites. In addition, we used the paired pulse technique to monitor facilitation and inhibition in this system. Kindling was found to induce a potentiation in the piriform field potential that lasted for at least 3 months (the period of the experiment) with little or no decay. Kindling also produced a decrease in paired pulse facilitation. In some animals the net facilitation was changed to a net depression. These results are consistent with the interpretation that kindling produces an increase in recurrent inhibition in the piriform cortex. The paired pulse measures, however, returned to near baseline levels over the 3-month test period.

Animals↗
PubMed1991

Activation of the NMDA receptor: a correlate in the dentate gyrus field potential and its relationship to long-term potentiation and kindling.

Stimulation trains, but not stimulation pulses, are capable of inducing long-term potentiation (LTP). In this paper we report experiments designed to examine, in chronic preparations, the characteristics of a component unique to the train-evoked response. Stimulation trains applied to the perforant path evoked population EPSP's and population spikes in the dentate gyrus that were nearly identical to those evoked by single pulses of comparable intensity. The trains also triggered a prolonged potential, negative at the dendritic pole of our electrodes, which far outlasted the pulse-evoked response. We substracted pulse-evoked responses from these train-evoked responses which left us with a waveform that peaked at about 15 ms and lasted for about 50-70 ms. The GABA agonists, diazepam and sodium pentobarbital, had no significant effect on this component, but the NMDA antagonists, ketamine and MK-801, both depressed it by over 30%. The late component had a very low threshold, which might account for the frequent observation of LTP induction at very low thresholds. Also, the late component is reliably seen in all animals showing LTP, even in the occasional animals that show no population spikes. The late component did not appear to be affected by the induction of LTP, and was either not affected or was depressed following the completion of kindling. When the 'NMDA-component' of the train-evoked response was monitored, along with LTP, in an ascending intensity train series, it was found that both the NMDA-component and the LTP increased smoothly. There was no sudden appearance of the NMDA-component at the LTP threshold. The presence of an NMDA component in the field potential of the chronic preparation allows the monitoring of the levels of NMDA activation over prolonged periods.

Action Potentials↗
PubMed1991

Effects of leukemia inhibitory factor (LIF) on gene transfer efficiency into murine hematolymphoid progenitors.

We have investigated the effects of the cytokine leukemia inhibitory factor (LIF) on recovery and retroviral infection of murine hematopoietic stem cells maintained in short-term culture. Up to a two-fold increase in CFU-S13 recovery was observed, from 9.7 x 10(-5) cells in untreated controls to 17.6 x 10(-5) cells when 10U/ml LIF is added to the culture medium. Intermediate concentrations of LIF (.1U/ml and 1U/ml) were not significantly different from the control. Histological analysis of spleen colonies harvested thirteen days posttransplant demonstrated that LIF does not cause a detectable alteration in the differentiative potential of CFU-S13. The efficiency of retroviral-vector infection in CFU-S13 is also improved, from 15% (24/158) in untreated controls to 91% (116/127) at a LIF concentration of 10U/ml. LIF concentrations of .1U/ml and 1U/ml increased infection efficiency to 35% (14/40) and 71% (37/51), respectively. Analysis of proviral insertion sites in spleen colonies indicated that some CFU-S13 precursors were infected in the LIF-treated marrows, but no identical pairs were detected in the controls. Finally, long-term expression of provirally-encoded human adenosine deaminase (hADA) was measured in hematopoietic tissues of bone marrow transplant recipients six months posttransplant. In all tissues analyzed (spleen, thymus, bone marrow, splenic B cells, peritoneal macrophages, and blood) differentiated progeny of LIF-treated marrows had higher levels of hADA than untreated controls. Tenfold increases in levels of hADA are detected in some tissues, but levels were variable. These experiments demonstrate that LIF directly or indirectly enhances retroviral infection efficiency of hematopoietic stem cells, and might be used to improved existing gene transfer protocols.

Adenosine Deaminase↗
PubMed1991

Characterization of recombinant helper retroviruses from Moloney-based vectors in ecotropic and amphotropic packaging cell lines.

We have characterized the recombinant replication-competent retrovirus (RCV) arising from p delta N2-derived vectors in the packaging cell lines psi 2 (ecotropic) and PA317 (amphotropic). Detailed restriction patterns and sequence of the envelope region of these RCVs has indicated that they arose from recombination events between the virus plasmids used to create the packaging cell line and the vectors. There was no evidence of recombination involving endogenous murine retroviral sequences in the packaging cell line or in transduced hematopoietic cells. In addition, we have confirmed that the mutation of the start codon of the pXM5(N2) derivatives gag+ sequence drastically decreased the occurrence of RCV production. These results offer encouragement that the risk of RCV production can be adequately decreased in gene therapy applications of defective retrovirus vectors.

Adenosine Deaminase↗
PubMed1991

Gene transfer of adenosine deaminase into primitive human hematopoietic progenitor cells.

The inherited deficiency in adenosine deaminase (ADA), which results in severe combined immunodeficiency, is generally regarded as an optimal model for the development of human somatic gene therapy. The ideal target for the correction of ADA deficiency and other lympho-hematopoietic disorders would be the hematopoietic stem cell. We have used a combination of recombinant human interleukins-3 and -6 to stimulate the proliferation of primitive human hematopoietic progenitor cells during a period of co-cultivation with irradiated cells producing high titers of an ADA-transducing retroviral vector packaged in amphotropic particles. In a series of nine experiments, an average of 83% of the clonogenic progenitors (CFU-E and CFU-GM) were found to have acquired the transferred sequence as determined by polymerase chain reaction analysis. In addition, in two experiments, 24-44% of the clonogenic progenitors derived from long-term myeloid cultures 9 weeks post-transduction were found to contain vector sequence. The latter cells are derived from so-called "long-term culture-initiating cells" (LTC-IC), which are primitive cells probably related to hematopoietic stem cells. Moreover, the transduced ADA enzyme was found to be expressed in both normal and ADA-deficient erythroid colonies, and in the nonadherent cells of long-term bone marrow culture for at least 2 weeks at levels that approximate the endogenous ADA levels of normal erythroid cells. These results indicate that the ADA coding sequence can efficiently be introduced by retroviral gene transfer into both committed and primitive human hematopoietic progenitor cells, and that this will result in adequate expression of the transduced enzyme in the progeny of committed hematopoietic progenitors.

Adenosine Deaminase↗
PubMed1991

Evaluation of lymphoid-specific enhancer addition or substitution in a basic retrovirus vector.

Two novel retroviral vectors bearing lymphoid-specific enhancers were tested for improved expression of human adenosine deaminase (hADA) in tissue culture cells and in mouse bone marrow transplant recipients. These vectors carried either an added human T-cell receptor alpha-chain enhancer (delta N2TADA) or a substitution of the Moloney long terminal repeat (LTR) enhancer with the murine immunoglobulin mu heavy-chain first intron enhancer (delta N2 mu ADA). Each vector was produced at a titer of approximately 10(6) infectious units/ml and efficiently transduced hADA into murine fibroblast and myeloma cells in culture. No quantitative difference in expression was observed between the enhancer modified vectors and the basic retrovirus vector (delta N2ADA). In addition, each vector efficiently conferred hADA expression in lymphoid, myeloid, and erythroid cells of long-term transplanted mice. The majority of the transduced-marrow recipients demonstrated expression of the human enzyme for 4-8 months with each of the three vectors.

Adenosine Deaminase↗
PubMed1991

Television viewing and early initiation of sexual intercourse: is there a link?

Using data from the National Survey of Children, this paper examines the hypothesis that the amount of time children spend viewing television and the extent to which the content viewed is sexual in nature is related to the initiation of sexual activity. Several theories that would lead to this hypothesis are reviewed. The data do not provide any strong or consistent evidence for such links. However, some aspects of the context in which television is viewed are related to sexual activity. The authors suggest ways in which the design and measures could be strengthened to provide a more rigorous test of the hypothesis.

Adolescent↗
PubMed1990

Human adenosine deaminase expression in mice.

A replication defective retroviral vector containing a human adenosine deaminase (hADA) cDNA was produced by GP + E-86 packaging cells at high titer. We report long-term expression of hADA in the hematopoietic tissues of mice transplanted with bone marrow cells infected by in vitro co-cultivation with vector producing cells. Western analysis using an hADA-specific antibody allowed detection of the protein in the peripheral blood of all 37 transplanted mice for at least 9 weeks. Sixty-eight percent of the animals continued to express hADA in one or more of their hematopoietic tissues for the experimental period, and hADA was found in both spleen colonies and tissues of secondary recipients. There was provirus integration and expression in myeloid, erythroid, and lymphoid cell lineages, indicating extensive repopulation by the progeny of infected stem cells. The vector did not contain a selectable marker, and the infected stem cells did not have a competitive in vivo advantage. Nevertheless, we observed consistent gene transfer into hematopoietic stem cells and long-term expression of a human gene product in their progeny.

Adenosine Deaminase↗
PubMed1989

Expression vectors for human adenosine deaminase gene therapy.

Somatic gene transfer offers a possible new approach for treatment of human genetic disease. Defects affecting blood-forming tissues are candidates for therapies involving transfer of genetic information into hematopoietic stem cells. Adenosine deaminase (ADA) deficiency is being used as a model disease for which gene transfer techniques can be developed and evaluated. We describe here the construction and testing of 20 retroviral vectors for their ability to transfer and express human ADA in vitro and in vivo via a mouse bone marrow transplantation model. After infection of primary bone marrow with one fo these vectors (p delta NN2ADA), human ADA was detected in 60-85% of spleen colonies at day 14 and maintained long term in the blood of fully reconstituted mice. This system offers the opportunity to assess methods for increasing efficiency of gene transfer, for regulation of expression of foreign genes in hematopoietic progenitors, and for long-term measurement of the stability of expression in these cells.

Adenosine Deaminase↗
PubMed1988

Expression of human adenosine deaminase in murine hematopoietic cells.

Multiple replication-defective retrovirus vectors were tested for their ability to transfer and express human adenosine deaminase in vitro and in vivo in a mouse bone marrow transplantation model. High-titer virus production was obtained from vectors by using both a retrovirus long terminal repeat promoter and internal transcriptional units with human c-fos and herpes virus thymidine kinase promoters. After infection of primary murine bone marrow with one of these vectors, human adenosine deaminase was detected in 60 to 85% of spleen colony-forming units and in the blood of 14 of 14 syngeneic marrow transplant recipients. This system offers the opportunity to assess methods for increasing efficiency of gene transfer, for regulation of expression of foreign genes in hematopoietic progenitors, and for long-term measurement of the stability of expression in these cells.

Adenosine Deaminase↗
PubMed1985

Sex education and sexual experience among adolescents.

This paper examines the association between sex education and adolescent sexual behavior. Data from the 1981 National Survey of Children show that 15- and 16-year-olds who have been exposed to sex education are less likely to be sexually experienced, and are neither more nor less likely to discuss sex with parents at home. Retrospective or longitudinal data are needed to more directly test the casual link between sex education and experience.

Adolescent↗
PubMed1978

Purification and properties of gamma-glutamylcyclotransferase from human erythrocytes.

1. GAMMA-Glutamylcyclotransferase was purified 10000-fold from human erythrocytes. 2. The purification steps involved fractionation with (NH4)(2)SO(4) and chromatography on Sephadex G-75, DEAE-cellulose and hydroxyapatite. The purified enzyme was found to be homogeneous on density-gradient polyacrylamide-gel electrophoresis. 3. The maximum reaction rate was observed at pH9.0 and the apparent Km value for gamma-glutamyl-L-alanine was 2.2mM. 4. The molecular weight (25250) of the purified enzyme agreed well with the value (25500) in fresh haemolysates, indicating no apparent structural modification of the enzyme during purification. However, rapid processing of the blood through the initial (NH4)(2)SO(4) and Sephadex-chromatography steps was required to prevent formation of a high-molecular-weight aggregate with substantially lower specific activity. 5. gamma-Glutamylcyclotransferase catalyses the formation of 5-oxoproline from gamma-glutamyl dipeptides. The role of this enzyme in erythrocytes is of particular interest, because gamma-glutamyl-L-cysteine serves as a substrate for both gamma-glutamylcyclotransferase and glutathione synthetase. Thus the cyclotransferase could modulate glutathione synthesis.

Acyltransferases↗