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L Cox

Publications and source records attributed to L Cox.

At least 19 recordsLinked to original sources
PubMed2001

Nucleus accumbens, entorhinal cortex and latent inhibition: a neural network model.

A neural network model of classical conditioning (Schmajuk, Lam, and Gray, J. Exp. Psychol.: Anim. Behav. Process, 22, 1996, 321-349) is applied to the description of the neural substrates of latent inhibition. Experimental data suggest that latent inhibition might be controlled by a circuit that involves the hippocampus, the entorhinal cortex, the nucleus accumbens, and the mesolimbic dopaminergic projection from the ventral tegmental area to the accumbens. By mapping different nodes and connections in the model onto this brain circuit, computer simulations demonstrate that, in most cases, the model provides a good quantitative description of: (1) the impairment of latent inhibition by lesions of the shell of the nucleus accumbens; (2) the restoration of latent inhibition by haloperidol following lesions of the shell; (3) the preservation of latent inhibition by lesions of the core of the nucleus accumbens; (4) the facilitation of latent inhibition by combined shell core lesions and by core lesions with extended conditioning; (5) the impairment of latent inhibition following lesions of the entorhinal cortex or the hippocampus; and (6) the restoration of latent inhibition by haloperidol following lesions of the entorhinal cortex and ventral subiculum. In addition, the model is able to describe neural activity in the nucleus accumbens.

Animals↗
PubMed2001

Matrix metalloproteinases and aggrecanases cleave aggrecan in different zones of normal cartilage but colocalize in the development of osteoarthritic lesions in STR/ort mice.

OBJECTIVE: To map aggrecan cleavage by matrix metalloproteinases (MMPs) and aggrecanases in normal murine tibial articular cartilage (CBA strain) and in the development of spontaneous osteoarthritis (OA) in the STR/ort mouse and to assess the influence of sex hormone status on these conditions in gonadectomized STR/ort mice. METHODS: The distributions of neoepitopes of aggrecan generated by MMP (VDIPEN) and aggrecanase (NITEGE) cleavage were investigated by immunohistochemistry. RESULTS: VDIPEN neoepitope was detected mainly in the pericellular matrix of deep-zone chondrocytes in normal tibial cartilage from STR/ort and CBA mice. In early OA, VDIPEN immunostaining also localized to the pericellular matrix of chondrocytes at the site of the lesion. With increasing severity of OA lesions, VDIPEN immunostaining was also detected in the interterritorial matrix, close to the site of the lesion. In contrast, NITEGE mapped most strongly to the pericellular matrix of upper-zone chondrocytes in normal tibial cartilage. As with VDIPEN, NITEGE was strongly expressed in the pericellular matrix at the site of early OA lesions. With advancing OA, NITEGE colocalized with VDIPEN in both the pericellular and interterritorial matrices of chondrocytes adjacent to OA lesions and in those of the deep zones. Hormone status did not appear to influence the development of OA or the distribution of aggrecan neoepitopes in STR/ort mice. CONCLUSION: MMP- and aggrecanase-generated neoepitopes map predominantly to different regions in normal murine tibial cartilage. However, both groups of enzymes generate increased amounts of neoepitopes in pericellular and interterritorial matrix adjacent to histopathologic lesions of OA. Aggrecan degradation and the development of OA appear to be independent of sex hormone status in this model.

Aggrecans↗
PubMed2000

The HMG box transcription factor gene Sox14 marks a novel subset of ventral interneurons and is regulated by sonic hedgehog.

Cell-type diversity along the dorsoventral axis of the developing neural tube is influenced by factors secreted by groups of cells at the dorsal and ventral midline. Upon reception of these signals, precursor cells express specific sets of transcription factors which, in turn, play critical roles in cell-type specification. Here we report the cloning and characterization of Sox14, a novel and highly conserved member of the Sry-related Sox transcription factor gene family, in mouse and chick. Sox14 expression is restricted to a limited population of neurons in the developing brain and spinal cord of both species. Sox14 marks a subset of interneurons at a defined dorsoventral position adjacent to ventral motor neurons in the spinal cord. In vivo grafting of chick notochord tissue to ectopic positions adjacent to the developing spinal cord altered the expression domain of Sox14. Furthermore, expression of Sox14 in spinal cord explants was found to be regulated by Sonic hedgehog in a dose-dependent manner. These data implicate a novel class of transcription factors in dorsoventral cell-type specification in the spinal cord.

Amino Acid Sequence↗
PubMed2000

Natural soil colloids To retard simazine and 2,4-D leaching in soil.

Natural or synthetic sorbents for pesticides can be used to reduce contamination of soils and natural waters. The sorption of simazine and 2,4-D on montmorillonite minerals has been studied and their potential use to retard pesticide leaching in soil evaluated. Simazine and 2,4-D did not sorb on high-layer charge montmorillonite, whereas sorption on the lower layer charge montmorillonite SWy varied depending on the saturating cation. Simazine sorption increased in the order Ca(2+)SWy << K(+)SWy < Fe(3+)SWy. Simazine molecules sorb on hydrophobic microsites of the montmorillonite. Once protonated, further sorption through cation exchange takes place in the interlamellar space of the montmorillonite, as corroborated by X-ray diffraction and FT-IR studies. 2,4-D does not sorb on K(+)SWy or Ca(2+)SWy, but does sorb on Fe(3+)SWy, because the acidic character of this sorbent allows the molecular form of 2, 4-D to sorb by hydrogen bonding and/or by hydrophobic interactions. Leaching experiments in hand-packed soil columns indicate that simazine and 2,4-D application as a complex with FeSWy renders later breakthrough and lower maximum concentration peaks, and the total herbicide leached is lower than when applied as the pure analytical grade compound. These results suggest the possible use of natural soil colloids as sorbents for herbicides such as simazine and 2,4-D to retard pesticide leaching in soil, thus reducing their ground water contamination potential.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2000

Haloperidol reinstates latent inhibition impaired by hippocampal lesions: data and theory.

The effect of haloperidol administration on the impairment of latent inhibition produced by aspirative lesions of the hippocampus was examined in the rat eyeblink response preparation. During the preexposure phase, rats with hippocampal or control lesions were either exposed to a tone or allowed to sit in the training apparatus. During the conditioning phase, the tone was paired with an airpuff to the eye after the rats were injected with either saline or haloperidol. Although saline-injected rats with hippocampal lesions did not show latent inhibition, the phenomenon was reinstated in rats that received haloperidol injections. A possible locus of the interaction between hippocampal lesions and haloperidol is the nucleus accumbens. The reported data are well described by a neural network model of classical conditioning. This study contributes to the understanding of the neurophysiology of latent inhibition as well as the neuropsychological bases of schizophrenia.

Animals↗
PubMed2000

Sorption and photolysis studies in soil and sediment of the herbicide napropamide.

The influence of soil and sediment composition on sorption and photodegradation of the herbicide napropamide [N,N-diethyl-2-(1-naphthyloxy)propionamide] was investigated. Five soils and one sediment were selected for this study and the clay fractions were obtained by sedimentation. Sorption-desorption was studied by batch equilibration technique and photolysis in a photoreactor emitting within 300-450 nm wavelength with a maximum at 365 nm. Sorption increased with clay content and was not related to organic matter content. High irreversibility of sorption was related to the greater montmorillonite content. The presence of soil or sediment reduced photolysis rate due to screen effect and this process did not depend on solid composition but on particle size distribution.

Adsorption↗
PubMed2000

The impact of electron transport on the accuracy of computed dose.

The aim of this work was to investigate the accuracy of dose predicted by a Batho power law correction, and two models which account for electron range: A superposition/convolution algorithm and a Monte Carlo algorithm. The results of these models were compared in phantoms with cavities and low-density inhomogeneities. An idealized geometry was considered with inhomogeneities represented by regions of air and lung equivalent material. Measurements were performed with a parallel plate ionization chamber, thin TLDs (thermoluminescent dosimeters) and film. Dose calculations were done with a generalized Batho model, the Pinnacle collapsed cone convolution model (CCC), and the Peregrine Monte Carlo dose calculation algorithm. Absolute central axis and off axis dose data at various depths relative to interfaces of inhomogeneities were compared. Our results confirm that for a Batho correction, dose errors in the calculated depth dose arise from the neglect of electron transport. This effect increases as the field size decreases, as the density of the inhomogeneity decreases, and with the energy of incident photons. The CCC calculations were closer to measurements than the Batho model, but significant discrepancies remain. Monte Carlo results agree with measurements within the measurement and computational uncertainties.

Air↗
PubMed1999

Iron isotope biosignatures.

The (56)Fe/(54)Fe of Fe-bearing phases precipitated in sedimentary environments varies by 2.5 per mil (delta(56)Fe values of +0.9 to -1. 6 per mil). In contrast, the (56)Fe/(54)Fe of Fe-bearing phases in igneous rocks from Earth and the moon does not vary measurably (delta(56)Fe = 0.0 +/- 0.3 per mil). Experiments with dissimilatory Fe-reducing bacteria of the genus Shewanella algae grown on a ferrihydrite substrate indicate that the delta(56)Fe of ferrous Fe in solution is isotopically lighter than the ferrihydrite substrate by 1.3 per mil. Therefore, the range in delta(56)Fe values of sedimentary rocks may reflect biogenic fractionation, and the isotopic composition of Fe may be used to trace the distribution of microorganisms in modern and ancient Earth.

Earth, Planet↗
PubMed1999

Longitudinal study of leptin concentrations during puberty: sex differences and relationship to changes in body composition.

Leptin may have a role in the initiation of puberty and the regulation of subsequent weight gain, but this hypothesis has not been tested by longitudinal study. We report data from 40 normal children (20 boys and 20 girls) followed from 8-16 yr of age with hormone measurements and auxology every 6 months. Before the onset of puberty, leptin levels were similar in boys and girls: G1, mean (95% confidence interval), 2.63 (2.17-3.20) ng/mL; B1, 2.47 (2.08-2.94) ng/mL (P = 0.64) and increased with age in both sexes (B, 0.107 +/- 0.042; P = 0.02). With the onset of puberty, leptin levels increased in girls (B2-B5, P < 0.0005), but decreased in boys (G2-G5, P < 0.0005). Similar positive independent relationships were seen between leptin and fat mass in girls (B, 0.106 +/- 0.022; P < 0.0005) and boys (B, 0.121 +/- 0.020; P < 0.0005), and negative relationships were found with fat-free mass [girls: B, -1.104 +/- 0.381 (P < 0.005); boys: B, -1.288 +/- 0.217 (P < 0.0005)]. Girls gained more fat mass than boys, whereas boys gained more fat-free mass, and this explained the sex difference in leptin levels. Leptin levels correlated significantly with a large number of other hormones, but none was independent of changes in body composition. In girls, but not in boys, low leptin levels during prepuberty (B1) predicted subsequent gains in the percent body fat during puberty (r = -0.75; P = 0.005). The sexual dimorphism in leptin levels during puberty reflects differential changes in body composition. Prepubertal leptin levels in girls also predict gains in the percent body fat.

Adipose Tissue↗
PubMed1998

Isolation of isoproturon-degrading bacteria from treated soil via three different routes.

Three different isolation routes (flask enrichment/flask degradation assay, flask enrichment/microplate degradation assay, MPN assay/microplate degradation assay) were used to obtain pure cultures of bacteria which degraded isoproturon (3-(4-isopropylphenyl)-1,1-dimethylurea) as sole carbon and nitrogen source in a mineral salts medium from a field soil treated with isoproturon in the laboratory. All three isolation routes were successful, but the microplate assay of degradation was more successful than the flask assay. Characterization of 36 isolates indicated that they formed 16 distinct phenotypes (10 Gram-positive phenotypes, six Gram-negative phenotypes) which are likely to represent distinct species. Low concentrations of the degradation product 3-(4- isopropylphenyl)-1-methylurea (IPPMU) were occasionally found in the culture solutions. When provided as the sole source of carbon and nitrogen, the monomethyl degradation product was itself rapidly degraded by several of the isolates. Some isolates were also able to use the demethylated degradation product 3-(4-isopropylphenyl)-urea (IPPU) as sole source of carbon and nitrogen, although there was occasionally an extended lag-phase before rapid degradation commenced. One isolate was particularly active and degraded isoproturon, the monomethyl and demethylated degradation products of isoproturon, and demethylated the related phenylureas diuron and linuron.

Bacteria↗
PubMed1998

Effect of environmental estrogens on IL-1beta promoter activity in a macrophage cell line.

Environmental estrogens or estrogen disrupters have recently received a great deal of attention because of their potential health impact on reproductive tissues. Few, if any, studies have been made on the impact of these compounds on the immune system. We sought to determine the activities of various environmental estrogens on the modulation of the interleukin-1beta (IL-1beta) gene in a model monocytic cell line, hER + IL-1beta-CAT+. This cell line stably transfected with the human estrogen receptor, and an IL-1beta promoter construct fused to the CAT reporter gene allows us to monitor the effect of estrogenic compounds on IL-1beta promoter activity. 17beta-estradiol (E2) markedly enhanced lipopolysaccharide- (LPS) induced IL-1beta promoter-driven CAT activity in a dose-dependent manner. The mycotoxins alpha-zearalenol and zearalenone both exhibited full agonist activity, but at lower potencies, with EC50 values of 1.8 and 54 nM, respectively, compared with E2 at 0.5 nM. In addition, genistein was a very low-potency agonist, having an EC50 of 1.5 microM. Similar to the E2 response, the slope factors for alpha-zearalenol, zearalenone, and genistein were close to 3.0, suggesting positive cooperativity in the estrogenic response. The activity of the mycotoxins appeared to be mediated through the estrogen receptor, since both the antiestrogens H1285 and ICI 182,780 effectively inhibited their agonist activity in a dose-dependent manner. Representative environmental estrogenic compounds both from plant and industrial sources were also tested. Unlike the mycoestrogens, none of the compounds, with the exception of genistein, synergized with LPS to enhance IL-1beta promoter activity. When tested for antiestrogenic activity, the industrial compound 4-octylphenol was able to antagonize the response to E2; however, the response was three orders of magnitude less potent than H 1285. Naringenin, a plant flavonoid, showed little or no ability to antagonize the response to E2. Overall, the results show that some environmental estrogens that display agonist activity in reproductive tissue also have an effect on IL-1 gene expression in hemopoietic-derived tissue.

Animals↗
PubMed1998

S-phase arrest in mouse keratinocytes exposed to multiple doses of ultraviolet B/A radiation.

Exposure to solar ultraviolet (UV) radiation is believed to cause most human skin carcinomas. Despite the large body of evidence connecting UV exposure with skin cancer, the frequency and level of human exposure to repetitive doses of UV light will most likely continue for occupational and recreational reasons. By investigating the cellular response of keratinocytes to multiple, physiologically relevant doses of UV, we hope to better understand the processes involved in UV-induced skin cancer. In this study, we used a UV exposure model to investigate the cell-cycle response of keratinocytes exposed to multiple doses of UV-B/A radiation in which the UV-C component (wavelengths below 290 nm) had been filtered out. Our results indicated that exposure of asynchronous mouse keratinocytes to three doses of 200 J/m2 UV-B/A radiation at 30 min intervals produced an inhibition of DNA synthesis and S-phase arrest between 7 and 25 h after the last irradiation. The S-phase arrest was not due to a reduction in the level of cyclin E and A proteins but was accompanied by inhibition of cyclin-dependent kinase 2 (cdk2) activity. We observed a similar pattern of cdk2 inhibition induced by multiple UV-B/A irradiations in mouse embryo fibroblasts from p21WAF null mice, indicating that the inhibition of cdk2 was independent of p21WAF in these cells.

Animals↗
PubMed1995

A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata (CDPX) and implications for warfarin embryopathy.

X-linked recessive chondrodysplasia punctata (CDPX) is a congenital defect of bone and cartilage development characterized by aberrant bone mineralization, severe underdevelopment of nasal cartilage, and distal phalangeal hypoplasia. A virtually identical phenotype is observed in the warfarin embryopathy, which is due to the teratogenic effects of coumarin derivatives during pregnancy. We have cloned the genomic region within Xp22.3 where the CDPX gene has been assigned and isolated three adjacent genes showing highly significant homology to the sulfatase gene family. Point mutations in one of these genes were identified in five patients with CDPX. Expression of this gene in COS cells resulted in a heat-labile arylsulfatase activity that is inhibited by warfarin. A deficiency of a heat-labile arylsulfatase activity was demonstrated in patients with deletions spanning the CDPX region. These data indicate that CDPX is caused by an inherited deficiency of a novel sulfatase and suggest that warfarin embryopathy might involve drug-induced inhibition of the same enzyme.

Abnormalities, Drug-Induced↗
PubMed1994

Calcium-sensitive cytosolic phospholipase A2 (cPLA2) is expressed in human brain astrocytes.

Calcium-sensitive cytosolic phospholipase A2 (cPLA2) is responsible for receptor-mediated liberation of arachidonic acid, and thus plays an important role in the initiation of the inflammatory lipid-mediator cascade generating eicosanoids and platelet-activating factor. In this study we have investigated the cellular distribution of cPLA2 in brain using a monoclonal antibody raised against cPLA2 to immunostain tissue sections of human cerebral cortex. We have localized cPLA2 in astrocytes of the gray matter. Colocalization with glial fibrillary acidic protein (GFAP) confirmed that cPLA2 is associated predominantly with protoplasmic astrocytes. Astrocytes of the white matter, on the other hand, were not immunoreactive. In experiments using different human astrocytoma cell lines we found that cPLA2 can be immunochemically localized in UC-11 MG cells, but cannot be detected in U-373 MG cells. This finding is consistent with the observation that cPLA2 mRNA as well as cPLA2 enzymatic activity can be readily measured in UC-11 MG astrocytoma cells, yet cannot be detected in U-373 MG cells. Our data suggest that the astrocyte is a primary source of cPLA2 in the brain and provide further evidence for the importance of this cell type in inflammatory processes in the brain.

Adult↗
PubMed1993

Sézary syndrome with elevated serum IgE and hypereosinophilia: role of dysregulated cytokine production.

A 62-year-old man presented with a 4-year history of a pruritic erythematous rash. Initial workup was not diagnostic, and the rash was refractory to standard treatment. A complete blood cell count demonstrated a white cell count of 9100 cells/microliter with 61% polymorphonuclear neutrophils, 16% eosinophils, and 17% lymphocytes. A serum protein electrophoresis revealed an M spike identified as IgG kappa. His IgE level was 11,900 IU/ml. A bone marrow biopsy specimen demonstrated "atypical plasma cells" but was not diagnostic for myeloma. Peripheral blood smear was remarkable for highly convoluted lymphoid cells diagnostic for Sézary T cells. Consistent with this diagnosis, 89% of his peripheral blood CD2+ cells expressed CD4. The eosinophilia, elevated IgE level, and monoclonal gammopathy led to further investigations. Circulating adherent monocytes were 96% positive for presumed low-affinity IgE receptor expression as shown by surface IgE binding. In a 9-day lymphocyte coculture, the patient's T lymphocytes induced IgE production in vitro (1.25 ng/ml) by a normal donor's cultured B cells. A healthy donor's T cells failed to induce IgE production (0 ng/ml) in a similar culture system. In situ hybridization with an Sulfur-35-labeled cDNA probe revealed interleukin-4 mRNA expression by 84% and interleukin-2 mRNA expression by 62% of nonadherent peripheral blood mononuclear cells. Interleukin-5 mRNA was shown by reverse transcription and the polymerase chain reaction. These studies demonstrate a subject with Sézary T cell leukemia with hypereosinophilia and elevated IgE due to presumed enhanced interleukin-4 and interleukin-5 production by the Sézary T cells.

B-Lymphocytes↗