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Biomedical subjects

J L Jackson

Publications and source records attributed to J L Jackson.

At least 19 recordsLinked to original sources

An electrophysiological study of semantic processing in young and middle-aged academics.

This study explored age differences in the N400 component, described by Kutas and Hillyard as an index of semantic expectancy. A group of young students and a group of middle-aged academics read a number of congruent and incongruent sentences followed by a recognition task. Age differences were found in both accuracy and speed in the recognition task. The N400 elicited in the reading task was both delayed in latency and reduced in amplitude in the older group. These aging effects could not be attributed to early stimulus input processes because the N1 did not differ between the age groups. A re-averaging of the event-related potentials during reading as a function of subsequent recognition showed a small memory-related positivity for the younger group and a large memory-related positivity for the older group, suggesting a difference in the encoding strategies of the two groups. To check the generalizability of the results of this particular age group, a further task (a memory scanning task) was carried out. The results, a delayed P3b and an increased reaction time, matched those found in the literature.

Adult

Phorbol ester induces phosphorylation of the 80 kilodalton murine interleukin 1 receptor at a single threonine residue.

The cytoplasmic domains of some cell surface receptors become phosphorylated in cells treated with phorbol esters. The present study was undertaken in order to determine whether this is also true of the 80 kDa interleukin 1 receptor (IL1R). Recombinant murine IL1R, transfected into chinese hamster ovary (CHO) cells or murine fibroblasts, was immunoprecipitated from [32P]orthophosphate-labelled cells. IL1R phosphorylation was only detected in cells pretreated with phorbol 12-myristate 13-acetate (PMA) and occurred solely on phosphothreonine. In contrast to a previous report, little or no IL1R phosphorylation occurred in response to IL1. By using a truncated receptor and receptors in which threonine residues were changed to alanines, we established that Thr537, near the carboxy-terminus, is the major site of PMA-induced phosphorylation. The human IL1R has a different sequence at this locus, and is apparently not phosphorylated. Binding studies showed that PMA-induced phosphorylation had no discernible effect on ligand binding or internalization.

Amino Acid Sequence

Assessment of schizophrenic inpatients with the MCMI.

The Million Clinical Multiaxial Inventory (MCMI) Psychotic Thinking scale previously was found insensitive in the detection of schizophrenia. The MCMI also was shown to be susceptible to undetected "faking good." We hypothesized that the insensitivity of the MCMI Psychotic Thinking scale was due to an unwillingness of schizophrenic patients to report psychotic symptoms. The MCMI was administered to 258 male schizophrenic inpatients who were classified as symptom-reporters or nonreporters based upon whether they endorsed psychotic symptoms on a separate problem checklist. Willingness to report psychotic symptoms was a significant factor in MCMI Psychotic Thinking scale scores as well as many other MCMI scales.

Adult

Young adult women who report childhood intrafamilial sexual abuse: subsequent adjustment.

Young adult women who had experienced incest and a matched comparison group were examined for differences in interpersonal functioning, sexual functioning, self-esteem, and emotional adjustment. Those reporting incest reported significantly poorer general social adjustment, especially in dating relationships. They had significantly lower levels of sexual satisfaction, lower self-esteem, and distorted body images, as well as greater depression and lower positive affect. These characteristics may be related not only to the incest experience but to the general family environment in which incest occurred, as significant differences in family characteristics were also observed.

Adolescent

Retention of ligand binding activity by the extracellular domain of the IL-1 receptor.

The IL-1R on murine T cells is an 80-kDa cell surface glycoprotein which binds both IL-1 alpha and IL-1 beta. We have recently isolated a cDNA clone encoding this molecule. From the primary sequence mature receptor is predicted to be a 557 residue integral membrane protein with a 319 residue carbohydrate-rich extracellular region. We have constructed a cDNA clone encoding this region of the protein (residues 1 to 316). Expression of this cDNA in HeLa cells leads to secretion of a soluble IL-1 alpha binding protein into the culture medium. Quantitative binding experiments with the truncated receptor show that it possesses IL-1 binding properties which are indistinguishable from those of full length IL-1R. Gel filtration chromatography experiments show that a complex can be formed between a single truncated receptor molecule and a single IL-1 alpha molecule.

Animals

cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily.

Interleukin-1 alpha and -1 beta (IL-1 alpha and IL-1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis. A direct expression strategy was used to clone the receptor for IL-1 from mouse T cells. The product of the cloned complementary DNA binds both IL-1 alpha and IL-1 beta in a manner indistinguishable from that of the native T cell IL-1 receptor. The extracellular, IL-1 binding portion of the receptor is 319 amino acids in length and is composed of three immunoglobulin-like domains. The cytoplasmic portion of the receptor is 217 amino acids long.

Amino Acid Sequence

Affinity purification and chemical analysis of the interleukin-1 receptor.

Interleukins-1 alpha and -1 beta regulate the metabolism of cells through a common plasma membrane receptor protein. In this study, it is demonstrated that the interleukin-1 (IL-1) receptor from detergent solutions of EL-4 cells can be stably adsorbed to nitrocellulose with full retention of IL-1 binding activity. This assay system was used to monitor the purification of the IL-1 receptor and to investigate the effects of several chemical modifications on receptor binding activity. IL-1 receptors extracted from EL-4 6.1 C10 cells can be bound to and specifically eluted from IL-1 alpha coupled to Sepharose. The affinity chromatography method resulted in the identification by polyacrylamide gel electrophoresis and silver staining of a protein of Mr 82,000 that was present in fractions exhibiting IL-1 binding activity. Experiments in which the cell-surface proteins of EL-4 cells were radiolabeled and 125I-labeled receptor was purified by affinity chromatography suggested that the Mr 82,000 protein was expressed on the plasma membrane. N-Glycanase treatment of this material showed that 23-35% of the total Mr (82,000) of the receptor is N-linked carbohydrate.

Chromatography, Affinity

Soman-induced brain lesions demonstrated by muscarinic receptor autoradiography.

Repeated exposure of rats to sublethal doses of soman resulted in moderate to severe symptoms of anticholinesterase intoxication and a pronounced weight loss within a small subgroup of these animals. A consistent pattern of cell loss and extensive neuronal necrosis appeared in specific brain areas within this subgroup. This neuropathology was not noted in rats unless they showed marked symptoms of poisoning including a precipitous weight loss. Neuropathology was most notable in the piriform cortex and thalamus. Quantitative receptor autoradiography indicated that these subjects had a significant decrease in muscarinic receptors in the piriform cortex and thalamus. The ratio of the muscarinic receptor densities in soman-treated rats with lesions to soman-treated rats without lesions was 57%, piriform cortex; 64%, ventrolateral thalamus; and 50%, mediodorsal thalamus. These decrements are distinguished from adaptive down-regulation because they are larger, there is no indication of recovery and there is a correspondence between histological lesions and the areas with decreases in muscarinic receptors. Thus, quantitative receptor autoradiography provides, in addition to kinetic information and topographical distribution, radiohistochemical evidence of neuronal damage.

Animals

pH selectivity of N-ethylmaleimide reactions with opiate receptor complexes in rat brain membranes.

N-Ethylmaleimide (NEM) decreases opiate agonist binding presumably by blocking crucial sulfhydryl (SH) groups at receptor binding sites. At physiological pH, NEM decreased GTP and manganese regulation but increased sodium effects on [3H]D-Ala2-Met5-enkephalinamide (D-Ala enk) binding to rat brain membranes. To determine the apparent pK values of putative SH groups in opiate receptors that react with NEM, rat brain membranes were incubated with 100-250 microM NEM in buffers ranging from pH 4.5 to 8.0. Results showed that lowering pH below 6.5 reduced the NEM effect on opiate receptor functions and that the apparent pK values of NEM-reacting SH groups in binding and regulatory sites ranged between 5.4 to 6.0. Most of the total SH groups in brain membranes continued to react with NEM at low pH, so that when nonspecific SH groups were blocked by incubating membranes at pH 4.5 with NEM, opiate receptors became sensitive to very low concentrations (1 microM) of NEM.

Animals

Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman.

[3H]Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration.

Animals

Genu recurvatum in spastic cerebral palsy. Report on findings by gait analysis.

Using high-speed motion pictures, electromyography, a dynamic piezoelectric force plate, and computer analysis of the data, the gait patterns of fifteen children, four to sixteen years old, with spastic cerebral palsy and genu recurvatum were analyzed to determine the mechanisms producing genu recurvatum and the effect of fixed-ankle below-the-knee orthoses. In all children the recurvatum during stance phase began when the tibia stopped moving forward and disappeared when tibial movement resumed. In six patients (Group I), excessive activity of the calf muscles in response to the increasing dorsiflexion moment about the ankle produced by the foot-floor reaction force arrested the forward motion of the tibia. In six others (Group II), the contraction of the calf muscles was not sufficiently strong to resist the dorsiflexion moment and the tibia moved forward until maximum dorsiflexion had occurred and then stopped. In both instances recurvatum was produced when the femur continued to move forward over the stationary tibia and an extension moment was produced at the knee. In no patient did activity of the knee flexors prevent recurvatum, which was eliminated only by resumption of forward movement of the tibia. This movement of the tibia was produced either by heel-off (Group I) or by sudden unweighting of the limb due to opposite heel-strike (Group II). In Group I, when tibial motion stopped in the first half of stance phase the position of the hip rapidly changed from flexion to extension and there was forward leaning of the trunk, while in Group II the change from hip flexion to extension occurred with backward leaning of the trunk. The fixed-ankle below-the-knee orthosis, by preventing excessive dorsiflexion and plantar flexion, produced more normal moments about all joints, especially the knee. In the three children (Group III) whose recurvatum was permanently corrected by the brace, no explanation for the improvement was evident in these studies.

Adolescent