Biomedical subjects

W J Jackson

Publications and source records attributed to W J Jackson.

At least 37 records · Page 2Linked to original sources

PubMed1992

Effects of concomitant cholinergic and adrenergic stimulation on learning and memory performance by primates.

Physostigmine and other centrally-acting acetylcholinesterase inhibitors are currently being examined for their potential in the treatment of Alzheimer's Disease. The ability to employ this class of agents is limited by the potential for debilitating and dangerous side effects. Clonidine and related drugs have recently been demonstrated to enhance memory performance in monkeys. Clonidine also inhibits the function of cholinergic neurons in specific brain regions and reduces certain side effects of physostigmine. Seven adult macaque monkeys performing a delayed matching-to-sample (DMTS) task received regimens of increasing doses of clonidine and physostigmine on separate occasions to determine the 'best dose' of each agent in terms of enhanced memory performance. The best doses were combined as a single administration and performance compared to that using the two drugs alone. The combination regimen of clonidine and physostigmine was more effective than either drug alone in enhancing memory performance. Part of the benefit may have been due to the ability to employ significantly higher doses of physostigmine in the combination regimen. A single injection of the combination resulted in enhanced performance both on the day of administration as well as on the following day. These results are consistent with the ability of clonidine to limit the expression or intensity of certain physostigmine-induced autonomic side effects, while allowing the cognitive beneficial effects of the cholinesterase inhibitor.

Animals↗

PubMed1991

Lesions of nucleus basalis alter ChAT activity and EEG in rat frontal neocortex.

The EEG was recorded from frontal, parietal and visual cortices of sham-operated control rats and rats having ibotenic acid lesions of the nucleus basalis. Recordings were made during a period of rest and during stimulus-evoked desynchronization. Spectral power was determined using a Fast Fourier Transform routine; 3 artifact-free 4 sec epochs of resting activity and two 4 sec epochs of activated EEG were analyzed. Choline acetyltransferase activity (ChAT) was measured in each cortical area and was reduced in lesioned animals an average of 25% in frontal cortex, 19% in the parietal region and 10% in visual cortex. The percent of low frequency activity (1-12 Hz) in the frontal EEG was significantly greater in lesioned animals than in the control group during quiet rest; a significant correlation was found between ChAT activity and power in this band. Desynchronized activity was largely unaffected except for a reduction in 25-31 Hz activity in the frontal cortex of lesioned animals. EEG activity in both the parietal and visual areas was unchanged from control values.

Animals↗

PubMed1991

Clonidine enhances delayed matching-to-sample performance by young and aged monkeys.

Clonidine, an alpha-2 noradrenergic agonist, has been shown to alter cognitive performance in humans and animals. Included among the evidence are studies which differ in their conclusions regarding the question of whether clonidine administration improves delayed response (DR) performance by nonhuman primates. The present results indicated that clonidine administration to both young and aged monkeys results in a modest performance improvement as measured by one of the commonly employed versions of DR performance-delayed matching-to-sample (DMTS). The clonidine-induced enhancement of DMTS had a duration of at least 24 h in both age groups.

Aging↗

PubMed1988

Nicotine enhances delayed matching-to-sample performance by primates.

The non-human primate provides an excellent model for studies of learning and memory, and one particular test, the delayed matching-to-sample task, is performed in a similar manner by both humans and non-human primates. Five young adult macaques were employed in this study, displaying variable capacities for retention in the task. Baseline performance was very consistent and three levels of performance difficulties (95-100%, 80-85% and 65-75% correct choices) were employed by including several delay intervals (0-60 sec) in each session. A reproducible enhancement in performance by nicotine in macaques performing a delayed matching-to-sample task was demonstrated. Nicotine enhanced performance with an average increase of 10% at the longest retention delay interval. This beneficial effect of nicotine was abolished in animals pretreated with a low dose (0.5 mg/kg) of mecamylamine to block central nicotinic receptors. Selective blockade of peripheral nicotinic receptors with hexamethonium was without effect on the nicotine response. A high dose (2 mg/kg) of mecamylamine itself induced a marked inhibition of performance, while an equivalent dose of hexamethonium was without effect. These experiments point to the possibility that central nicotinic receptors may be exploited pharmacologically to enhance memory performance. In this respect it is interesting that nicotine was most effective at enhancing performance when recall was more difficult, that is, on the longer retention interval delays. This could signify that nicotine might be particularly effective in the most impaired individuals. Lastly, it is encouraging that the mecamylamine induced decrease in cognitive performance might provide a new model of memory impairment from which to study the pathogenesis and develop new pharmacological strategies for the dementias.

Animals↗

PubMed1987

On the role of the light-harvesting B880 in the correct insertion of the reaction center of Rhodobacter capsulatus and Rhodobacter sphaeroides.

The purple, non-sulfur photosynthetic bacteria Rhodobacter capsulatus and Rhodobacter sphaeroides have two types of pigment-protein complexes that absorb incident light and funnel it to the photochemical reaction center. One of these, B880, is present at an essentially constant ratio to the reaction center, while the abundance of the other, B800-850, varies with growth conditions. Independent work in our two laboratories has indicated that while the absence of B800-850 permits photosynthetic growth in both organisms, the lack of B880 produces a different phenotype in the two species. Thus R. sphaeroides is still photosynthetically competent when it lacks this complex, while R. capsulatus is not. This unanticipated difference in what appear to be very closely related organisms has caused us to reexamine the properties of the two mutants simultaneously, under identical conditions. We find that the original descriptions are indeed correct; the reaction center of R. capsulatus is not correctly inserted into the photosynthetic membrane in the absence of B880, while that of R. sphaeroides is.

Bacterial Proteins↗

PubMed1987

The effect of hypophysectomy, ACTH fragments and thalamic lesions upon kindled epilepsy.

Hypophysectomized rats showed aberrant and retarded rates of kindled epilepsy. In hypophysectomized rats administered adrenocorticotropic hormone (ACTH) subunits ACTH4-10 and ACTH1-24, the normal kindling pattern was restored. However, in hypophysectomized animals which also had lesions of the thalamus (nucleus parafascicularis), ACTH4-10 did not restore the normal pattern of kindling. There have been many conjectures that kindling may be a subcase of learning. These results are compatible with this hypothesis, since the same procedures act in an analogous fashion within avoidance conditioning paradigms.

Adrenal Glands↗

PubMed1987

Overexpression and DNA-binding properties of the mer-encoded regulatory protein from plasmid NR1 (Tn21).

In plasmid NR1 the expression of genes involved in mercury resistance (Tn21) is regulated by the trans-acting product of the merR gene. An in vivo T7 RNA polymerase-promoter overexpression system was used to detect a protein of approximately 16,000 daltons encoded by the merR reading frame. Overexpressed MerR constituted about 5% of labeled proteins. An in vitro MerR-mer-op (mer-op is the mer operator and promoter region) gel electrophoresis binding assay established that the binding site for MerR was located between the putative -35 and -10 sequences of the promoter for the mer structural genes. A nonsense mutation in the carboxyl half of MerR resulted in the loss of biological function and the loss of in vitro mer-op binding properties.

Bacterial Proteins↗

PubMed1986

Effects of various hippocampal lesions on monkey plasma cortisol levels in two experimental conditions.

The plasma cortisol levels of Rhesus monkeys with anterior, posterior, or near-total hippocampal lesions were compared to controls during two separate stressful conditions. In the first condition, each monkey was placed for the first time in a primate restraint chair for 72 h. In the second condition each monkey performed a complex behavioral task (titrating shock avoidance) to control the intensity of frequent footshock for a 24-h period. Control subjects had either no surgical operation or else surgical exposure of the hippocampus with no hippocampal lesion. They manifested lower plasma cortisol levels during shock avoidance compared with during the chair condition. Subjects with posterior hippocampal lesions manifested the same pattern but near-totally hippocampectomized subjects showed an opposite pattern with cortisol levels higher in the shock avoidance condition compared with the chair condition. Subjects with anterior hippocampal lesions had similar cortisol levels in both conditions. Thus hippocampal modulation of corticosteroid levels may depend on the specific condition under which such levels are measured, and may be relatively more subserved by anterior compared with posterior hippocampus in the monkey.

Animals↗

PubMed1985

The structure of the mer operon.

The DNA sequence has been determined for a 3.8-kb region which encodes the mercury-resistance (mer) operon of the IncFII plasmid NR1. The sequence reveals 4 open reading frames which could encode proteins of 12,522, 9,429, 14,965, and 58,912 d corresponding to the 4 previously described Hg-inducible proteins detected in minicells carrying mer+ plasmids. The Hg(II) reductase protein sequence is about 90% homologous to that of Tn501, but the DNA sequence shows a homology of 60-70% to that of Tn501 except for short regions of very high homology. The entire mer region is 63.4% G-C overall. The region encoding the merR (positive regulatory) function has 3 possible open reading frames, 2 of which overlap in one direction and the third of which reads in the opposite direction. Attempts to visualize the polypeptide(s) encoded by the merR cistron were unsuccessful.

Bacteria↗

PubMed1984

Regional hippocampal lesions alter matching by monkeys: an anorexiant effect.

Findings showed that monkeys with middle, but not anterior or posterior hippocampal damage, are impaired in ability to acquire matching-to-sample, if training is conducted without error correction. All groups except this middle hippocampal lesion group abandoned the spatial strategy and achieved above-chance levels of matching within 6,000 trials. Although monkeys with anterior and posterior hippocampal lesions abandoned spatial strategies of responding at the normal rate, they, along with the middle hippocampal lesion group began to show a short-session-effect which coincided with just-above-chance matching performance. Affected monkeys, although able to correctly match, would not consume the food pellet reward, showed signs of anxiety, and performed only 25 of the usual 200 problems offered each day. None of the surgical control or unoperated control monkeys exhibited the short-session-effect. The untreated short-session-effect continued for as long as two months, but was always quickly alleviated by oxazepam, diazepam, or chlordazepoxide hydrochloride.

Amygdala↗

PubMed1984

Behavioral testing of progenies of Tx (hypothyroid) and growth hormone-treated Tx rats: an animal model for mental retardation.

Virgin Sprague-Dawley Holtzman rats were rendered Tx (hypothyroid) by radiothyroidectomy and maintained on 1.0 microgram T4 (thyroxine) per 100 g BW until pregnant. One-half of these Tx animals were administered 0.5 IU of growth hormone (GH) during the last 10-11 days of gestation as GH secretion is especially deficient in Tx rats. Untreated, food restricted to the level consumed by the Tx-only rats, GH-treated euthyroid, and T4-treated until pregnant animals served as controls. The animals were allowed to go through parturition and each litter was reduced to no more than 6 pups by removing pups for tissue weights and protein analyses at 1 and 5 days of age. The pups were weaned at 22 days of age and 2 animals per litter were utilized for behavioral testing between 40 and 60 days of age. At the end of the behavioral testing period the 60-day-old offspring were sacrificed to obtain tissue weights and protein concentrations. The behavioral tests were based on the ability of the animals to learn a Lashley's type 3 enclosed alley maze and their spontaneous activity was measured in stabilimeter cages. The animals were fasted overnight on alternate days and then given a food reward upon traversing the maze. This allowed for 10 separate trials in both the Lashley maze and the stabilimeters over the 20-day period from 40 to 60 days of age. Our previous studies have shown the fetuses and progenies of Tx-only mothers to have multiple metabolic defects including reduced rates of protein synthesis and tissue protein concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

The DNA sequence of the mercury resistance operon of the IncFII plasmid NR1.

The DNA sequence has been determined for a 3.8-kilobase region which encodes the mercury resistance (mer) operon of the IncFII plasmid NR1. The sequence reveals four open reading frames which could encode proteins of 12,391, 9,429, 14,965, and 58,781 daltons. On the basis of their sizes, amino acid compositions, hydropathicities, and estimated isoelectric points, the peptides encoded by these open reading frames correspond to the four previously described Hg-inducible proteins detected in minicells carrying mer+ plasmids. The NR1 mer locus is 63.4% GC overall, and the Hg(II) reductase protein sequence is 90% homologous to that of Tn501. The region encoding the merR (positive regulatory) function has three open reading frames. The smallest of these possible merR peptides (6,457 daltons) begins approximately 280 bp to the right of the adjacent IS1b and reads towards the structural genes of the mer operon. The next largest reading frame (13,139 daltons) in the merR region begins 37 bp to the left of the beginning of the smallest peptide and also reads towards the structural genes. The largest reading frame (15,907 daltons) in the merR region lies on the complementary strand and reads away from the structural genes towards IS1b. Although attempts to visualize the merR gene product were not successful, in vitro mutagenesis allows us to eliminate the largest reading frame as a merR candidate. We were also able to show that approximately 50% of the smallest detectable mer peptide (9,429 daltons) is located in the periplasm.

Bacterial Proteins↗

PubMed1982

Polypeptides encoded by the mer operon.

HgCl2-induced polypeptides synthesized by Escherichia coli minicells containing recombinant or natural HgR plasmids were labeled with [35S]methionine and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. All plasmids examined encoded two heavily labeled, HgCl2-inducible polypeptides of 69,000 and 12,000 daltons. Most plasmids also encoded two additional HgCl2-inducible proteins in the 14,000- to 17,000-dalton range. Antiserum prepared against a purified mercuric ion reductase reacts with the 69,000-dalton polypeptide and a minor 66,000-dalton protein seen in several different HgR minicells. Recombinant plasmids constructed from portions of mer DNA from the IncFII plasmid NR1 were also analyzed in the minicell system. Five HgCl2-inducible polypeptides (69,000, 66,000, 15,100, 14,000, and 12,000 daltons) were synthesized in minicells carrying pRR130, a recombinant derivative containing the EcoRI-H and EcoRI-I restriction fragments of NR1. The EcoRI-H fragment of NR1 encodes the three small mer proteins of 15,100, 14,000, and 12,000 daltons and the amino-terminal 40,000 daltons of the mercuric ion reductase monomer.

Bacterial Proteins↗

PubMed1982

Biochemical characterization of HgCl2-inducible polypeptides encoded by the mer operon of plasmid R100.

Minicells carrying the subcloned mer operon from plasmid R100 were pulse-labeled with [35S]methionine, and the labeled polypeptides were analyzed at various subsequent times by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The Hg(II) reductase monomer encoded by plasmid R100 occurred as two proteins of 69 and 66 kilodaltons (kd). The minor 66-kd protein is a modified form of the 69-kd protein. This modification occurs in vivo. Both of these mer proteins are found in the soluble fraction of the cell; however, the 66-kd protein appears to have a slight affinity for the cellular envelope. Both the 69- and 66-kd mer proteins have pI values greater (pI = 5.8) than that reported (pI = 5.3) for the analogous monomer encoded by plasmid R831. The 15.1- and 14-kd mer proteins are localized in the inner membrane and are probably elements of the mer-determined Hg(II) uptake system. These two mer membrane proteins, which are antigenically unrelated to the Hg(II) reductase monomer, are quite basic (pI values greater than 7.8). The 12-kd mer protein is also a basic polypeptide that is present in the soluble fraction of the cell. Unlike the two membrane-bound mer proteins, the 12-kd mer protein is processed from a 13-kd precursor.

Bacterial Proteins↗

PubMed1980