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Biomedical subjects

M C Wilson

Publications and source records attributed to M C Wilson.

At least 127 records · Page 7Linked to original sources
PubMed1986

Comparative discriminative stimulus properties of dl-cathinone, d-amphetamine, and cocaine in rats.

The discriminative stimulus properties of dl-cathinone (dl-CAT), d-amphetamine (d-A), and cocaine (COC) were compared and effects of haloperidol pretreatment on these properties were studied in rats. The ED50's of each drug were also determined. Stimulus generalization (i.e., greater than 75% of responses occurring on the drug lever) occurred with each of the three training drugs to all three test drugs. The degree of generalization was less between d-amphetamine and dl-cathinone than between d-amphetamine and cocaine or between cocaine and dl-cathinone. No significant differences were observed among the ED50's of each test drug obtained in all three training groups. Pretreatment with haloperidol failed to alter the stimulus properties of dl-cathinone. Haloperidol administration did partially antagonize the stimulus complex induced by d-amphetamine and cocaine. It is concluded that all three agents share somewhat similar but not identical, stimulus properties. The stimulus properties of the training dose of d-amphetamine may be somewhat different from those of dl-cathinone and may be more dependent on functional dopaminergic pathways.

Alkaloids↗
PubMed1986

The effects of clonidine on food consumption and food competition in male stumptail macaques (Macaca arctoides).

The effects of clonidine on noncompetitive and competitive feeding were examined in three adult male stumptail macaques (Macaca arctoides). Noncompetitive feeding was examined when the subjects were individually-caged or group-caged. Clonidine (1.0 mg/kg) administered IM substantially increased food consumption over control values in all subjects in both housing situations. The effects of clonidine on competitive feeding behavior were evaluated in the group-caged environment. Food competition was assessed by recording the number of chows retrieved from a common food box by each subject. Food retrieval was increased in the lowest-ranking subject when clonidine was administered to all subjects. Retrieval decreased in the middle-ranking subject and was unchanged in the highest-ranking subject. Administration of clonidine to individual subjects did not increase food retrieval. It is concluded that since the hyperphagic property of clonidine was only apparent during noncompetitive food-getting, that other drug-behavioral interactions prevented an increase in food retrieval during competitive situations.

Animals↗
PubMed1986

Patterns of gene expression in the murine brain revealed by in situ hybridization of brain-specific mRNAs.

Biochemical differences between neuronal cell populations of the mammalian brain, including selection of neurotransmitters and distinct neural antigens, suggest that the regulation of gene expression plays an important role in defining brain function. Here we describe the use of in situ hybridization to identify cDNA clones of highly regulated mRNA species and to define directly their pattern of gene expression in brain at both gross morphological and cellular levels. One of the selected cDNA clones, pMuBr2, detected a single 3.0 kb mRNA species, which from in situ hybridization appears specific to oligodendroglia cells. Three other cDNA clones, pMuBr3, 8 and 85, identified polyadenylated mRNA transcripts expressed by neuronal cells of the murine brain. Viewed at the gross morphological level, the mRNAs hybridizing to these cDNA sequences exhibit different patterns of abundance distinguishing such brain structures as pons, anterior thalamus, hippocampus, basal ganglia and anterior lobe of the neuroendocrine pituitary gland. At the cellular level, in situ hybridization revealed that these mRNAs are differentially expressed by morphologically and functionally distinct neurons of the cerebellum and hippocampal formation. When examined in the context of known brain function, however, the regulated expression of the neuron-specific mRNAs does not correlate simply with known cellular morphology or previously demonstrated neuronal relationships suggesting novel patterns of gene expression which may contribute to brain function.

Animals↗
PubMed1986

Structure of the human Ia-associated invariant (gamma)-chain gene: identification of 5' sequences shared with major histocompatibility complex class II genes.

The human gene encoding the Ia-associated gamma (or invariant) chain was isolated by screening a genomic library in phage lambda with cDNA probes. The frequency of positive clones in the library, the overlapping restriction maps of the cloned fragments, and the patterns of genomic hybridization suggested that the gamma-chain gene exists as a single copy per haploid genome. The gene consists of 8 exons, spanning approximately 12 kilobases of DNA. All exon sequences were in an open reading frame, contained appropriate splice junction sequences, and encompassed the entire sequence of full-length gamma-chain mRNA, suggesting that the gene we isolated is most likely functional. Furthermore, "CAAT"-type and "TATA"-type promoter sequences were found at the expected positions upstream from the proposed cap site. The organization of the gamma-chain gene has none of the distinctive features of the immunoglobulin superfamily of genes, of which Ia alpha and beta chains are members. Therefore, the evolutionary origins, and perhaps the functions, of the Ia gamma chains are distinct from those of the other two Ia subunits alpha and beta. Despite the unrelatedness of these genes, consensus sequences found approximately 150 base pairs upstream from all the Ia alpha- and beta-chain genes sequenced to date were also found in analogous positions in the gamma-chain gene, suggesting a possible role in the coregulation of expression of these genes.

Base Sequence↗
PubMed1986

The requirement for polymorphonuclear leukocytes in the late asthmatic response and heightened airways reactivity in an animal model.

The antigen-induced late asthmatic response (LAR) and subsequent heightened airways reactivity after this response have been associated with increased airways inflammation. Employing an animal model of the LAR in rabbits previously developed in our laboratory, 3 phases of experiments were performed to investigate the role of polymorphonuclear leukocytes (PML) in the LAR and heightened reactivity. In all 3 phases, airways reactivity to histamine and bronchoalveolar lavage analysis were performed 3 days before and 3 days after bronchial challenge with ragweed extract. In Phase 1, 2 groups of rabbits receiving nitrogen mustard were studied: an immune group received immune serum containing antiragweed IgE, and a control group received nonimmune serum. In Phase II, nitrogen mustard was administered to immune rabbits during aortic occlusion to allow the lungs to be exposed to nitrogen mustard while limiting exposure of the bone marrow to this drug, preventing depletion of PML. In Phase III, both an immune and a nonimmune group of rabbits received nitrogen mustard as in Phase I; however, prior to antigen challenge, they were repleted with a neutrophil-rich population of PML. In all experiments, no group of control (nonimmune) rabbits, whether depleted or repleted of PML, developed an immediate asthmatic response (IAR) or a LAR. In addition, no significant increases in lavage cells or airways reactivity occurred after ragweed challenge. In contrast, those animals receiving immune serum and nitrogen mustard developed an IAR; however, no LAR occurred, and no significant change in airways reactivity was observed. Rabbits receiving immune serum and nitrogen mustard with aortic occlusion developed an IAR and LAR, and airways reactivity increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Anorectics and the set point theory for regulation of body weight.

Considerable interest has been recently expressed in the theory that there is a set point which is responsible for regulating body weight. Supporters of this theory propose that anorectics reduce such a set point, and that food consumption is then secondarily affected to achieve a new body weight. We report in this study data obtained in rats which favor the set point theory. The major support for this conclusion is derived from an experiment in which the 'appetite suppressor,' fenfluramine, was administered in a paradigm which dissociated its ability to reduce food intake from its capacity to decrease body weight. Under these conditions, the body weight of a control group increased by 17 g; whereas that of the fenfluramine group was reduced by 11 g. In general, the fenfluramine-treated subjects ate as much as the controls. However, the controls increased body weight; whereas, the treated subjects demonstrated a decrease rather than an increase in this parameter. This result suggests that the fenfluramine group did not gain weight because the drug-altered 'set point' was lower in this group than in the controls.

Animals↗
PubMed1986

Inflammation and the late phase reaction in asthma: the effect of polymorphonuclear leukocyte depletion on airways obstruction and bronchial hyperreactivity in an animal model.

Increases in airway reactivity noted after antigen exposure in which a late asthmatic response (LAR) develops may be related to pulmonary inflammation. Employing an animal model of the LAR developed in our laboratory, we conducted experiments to determine if depletion of polymorphonuclear leukocytes (PMLs) would ablate the LAR and inhibit subsequent increases in airways reactivity. Four groups of ten animals each were studied. The first group was given immune sera (I) containing anti-ragweed IgE. The second group received non-immune sera (NI). A third group of animals received immune sera plus nitrogen mustard (I + NM), while a fourth group received non-immune sera plus nitrogen mustard (NI + NM). Airways reactivity to histamine and the evaluation of different cell types in bronchoalveolar lavage fluid (BALF) were determined three days before and three days after bronchial challenge with ragweed extract (RWE). No control rabbit (NI or NI + NM) developed either an immediate asthmatic response (IAR) or an LAR, and no significant increases occurred in their airways reactivity or cells in lavage fluid after bronchial challenge with RWE. In contrast, the sensitised rabbits not given nitrogen mustard developed an LAR and airways reactivity increased markedly three days later. Those animals receiving immune sera and nitrogen mustard developed an IAR; however, no LAR occurred and no significant change in airways reactivity ws observed. BALF analysis seventy-two hours after ragweed challenge in the animals that received immune sera showed a significant increase in PMLs. However, there was no significant increase on BALF PMLs in the animals receiving immune sera and nitrogen mustard.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗
PubMed1985

The effect of previous d-amphetamine treatment on the disposition and lethality of fenfluramine in the rat.

In an earlier study, it was found that a 15-day ip postfeeding session d-amphetamine treatment rendered an apparent "tolerance" to the feed intake suppressant effects of fenfluramine. The purpose of the present study was to determine if such d-amphetamine treatment altered the disposition of fenfluramine in a way which might account for this decrement in the feed intake suppressant effect of fenfluramine. In addition, the effect of d-amphetamine on fenfluramine toxicity was also examined in an attempt to further characterize and correlate fenfluramine dispositional changes. It was found that plasma and, to some extent, brain concentrations of fenfluramine were elevated in the d-amphetamine-treated rats as compared to a saline control group. The acute, ip LD50 for fenfluramine in d-amphetamine-treated rats was 68 mg/kg (95% CI = 64.8 to 71.4), a value significantly lower than that observed in the saline-treated animals (97 mg/kg; 95% CI = 93.3 to 100.9). The overall results of this study suggest that the anorectic tolerance conferred toward fenfluramine by previous subchronic treatment with d-amphetamine does not result from decreased plasma or brain concentrations of fenfluramine. In fact, such concentrations are increased by prior d-amphetamine treatment, and this increase may in part account for the increased lethality of fenfluramine observed in these animals.

Amphetamine↗
PubMed1985

Genetic elements used for a murine lupus anti-DNA autoantibody are closely related to those for antibodies to exogenous antigens.

The mRNAs encoding heavy and light chains of a hybridoma-derived monoclonal IgM kappa anti-DNA autoantibody from lupus-prone MRL/Mp-lpr/lpr mice (Ighj) have been transcribed into cDNA copies and molecularly cloned, and their complete nucleotide sequences have been determined. The mRNA for the heavy chain variable region, including leader peptide and 5' untranslated region, is transcribed from a heavy chain variable region (VH) gene closely related (and possibly allelic) to VH genes of the C57BL/6 (Ighb) nitrophenyl antibody family. The deduced amino acid sequence corresponding to the light chain variable region of this autoantibody shows extensive similarities with non-autoantibody molecules of the V kappa 1 group, suggesting a common variable gene origin. The joining segments, constant regions, and 3' untranslated regions of both the heavy and light chain mRNAs are nearly identical to corresponding sequences of non-autoantibodies from normal mice. Our findings suggest that this anti-DNA autoantibody originated from the same germline repertoire as antibodies to exogenous antigens.

Animals↗
PubMed1985

Alteration of the neurochemical effects of fenfluramine by previous treatment with d-amphetamine.

It was found in an earlier study that a 15-day IP subacute d-amphetamine treatment rendered an apparent "tolerance" to the food intake suppressant effects of fenfluramine. The purpose of the present study was to determine if the neuronal substrate on which fenfluramine supposedly acts to produce a decrement in food consumption was altered by the previous treatment with d-amphetamine. The time course effects (0-90 min) of a single IP injection of 10 mg/kg fenfluramine on brain monoamines in saline-treated rats included a significant lowering of serotonin in all brain regions examined. Although the serotonin depleting actions of fenfluramine in the d-amphetamine-treated rats generally paralleled those seen in the saline group (i.e., as in the hypothalamus), no such effects were noted in regions where baseline values (see below) were already lowered by d-amphetamine treatment (i.e., pons-medulla, thalamus, and substantia nigra). Norepinephrine and dopamine depletions were observed in the pons-medulla and hypothalamic areas after fenfluramine administration in the saline-treated rats, but fenfluramine caused no decreases in hypothalamic dopamine or in pons-medulla and hypothalamic norepinephrine content in rats previously treated with d-amphetamine. Analysis of the baseline amine levels (i.e., values in the d-amphetamine and saline-treated rats before fenfluramine was given) indicated that the repeated d-amphetamine treatment generally lowered norepinephrine in most brain regions, serotonin in the pons-medulla, substantia nigra and thalamus, and dopamine in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The Gv-1 locus coordinately regulates the expression of multiple endogenous murine retroviruses.

The analysis of the normal expression of endogenous retroviral sequences in congenic 129 GIX+ and GIX- mouse strains suggests the action of a regulatory element, encoded by Gv-1, functioning in trans to control the expression of these sequences. At steady state, the abundance of polyadenylated retroviral transcripts of different length cosegregates with the Gv-1 genotype. The presence of low but detectable quantities of these transcripts in antigen-negative mice indicates however, that Gv-1 may be distinct from the structural genes encoding retroviral proteins. We report here that retroviral transcripts, derived from distinct proviruses, are expressed in a tissue-specific manner and are coordinately regulated by the Gv-1 locus. The structure of several of the abundant transcripts demonstrates further that they are transcribed from independent defective endogenous proviral genomes exhibiting extensive deletions of env coding regions as well as modified U3 regions distinct from those found in exogenous retroviral transcripts.

Animals↗
PubMed1985

Normal expression of polymorphic endogenous retroviral RNA containing segments identical to mink cell focus-forming virus.

In the absence of infectious virus, strains of mice express polyadenylated RNA transcripts homologous to the genome of murine leukemia virus. In addition to transcripts consistent with full-length and spliced env retroviral RNAs, several unique RNA species which lack the env sequence accumulate in a tissue-specific manner. These RNA species are presumed to be transcribed from endogenous retroviral sequences that constitute the bulk of the murine leukemia virus-related sequences in the murine genome. To determine the relationship of these RNA transcripts to infectious murine leukemia virus and the precise structural basis of the heterogeneity observed for the env-lacking transcripts, we isolated and sequenced cDNA recombinants representing the RNAs expressed in strain 129 GIX+ mice. Comparisons of the nucleotide sequences demonstrated that the endogenous retroviral transcripts differed in pol, p15E, and R-peptide regions by single nucleotide changes. In contrast, the gp70-coding regions of two cDNA clones derived from epididymis and liver were completely homologous over a 599-nucleotide overlapping sequence. The structures of env-lacking transcripts were examined in two independent cDNA clones, and each was found to contain a different deletion that was potentially mediated by seven-base pair direct repeats in the intact sequence. The extensive sequence homology between cDNAs allowed construction of a cumulative sequence map of the 3' end of an intact endogenous retroviral transcript. A comparison of this sequence with infectious ecotropic and mink cell focus-forming viruses revealed that the endogenous transcripts are highly homologous with the substituted portions of leukemogenic mink cell focus-forming viruses and therefore further define the boundaries of recombination required to generate these viruses.

Amino Acid Sequence↗
PubMed1985

Clonidine-induced alterations in feeding in deprived rats.

The ability of systemically administered clonidine to alter 3-hr food consumption in 21-hr food deprived male rats was investigated. Clonidine (12.5, 25, 50, and 100 mcg/kg) administered IP 10-min prior to feeding failed to affect this behavior. However, a dose of 200 mcg/kg significantly decreased feeding. This same dose when given for 7 consecutive days resulted in decreased feeding but only during the initial four sessions. This same dosage and treatment schedule also resulted in a reduction in locomotor activity, but only on the initial day of dosing. A comparison of these two results suggests that part of the depression in feeding resulted from a general decrease in activity. The acute effect of the 200 mcg/kg dose of clonidine was enhanced by morphine pretreatment, unaffected by treatment with naloxone or phenoxybenzamine and antagonized by treatment with tolazoline. This latter data suggests that the depressant action of clonidine on feeding results primarily from an action on noradrenergic systems, and in particular alpha 2 receptors.

Animals↗
PubMed1984

The effects of dl-cathinone, d-amphetamine and cocaine on avoidance responding in rats and their interactions with haloperidol and methysergide.

The effects of dl-cathinone (dl-CAT), d-amphetamine (d-A), and cocaine (COC) on conditioned shock avoidance responding and their interactions with haloperidol and methysergide on this behavior were studied in male Wistar rats. All three stimulants produced significant increases in intertrial interval (ITI) responding and in the number of avoidance responses and a decrease in avoidance latencies. These actions were antagonized by pretreatment with haloperidol (0.07 and 0.15 mg/kg, IP). Pretreatment with methysergide (1.0 and 2.0 mg/kg, IP) increased the effects of all three stimulants on ITI responding, but not on the other two parameters. These results suggest that the effects of these stimulants on avoidance responding may be mediated by dopaminergic systems. In addition, these stimulant-induced changes on ITI responding probably also involve actions on serotonergic systems.

Alkaloids↗
PubMed1984

The effects of several anorexigenics on monkey social behavior.

The effects of fenfluramine HCl, diethylpropion HCl, and methylphenidate HCl on social behavior were studied in a heterosexual group of stumptailed monkeys (M. arctoides). Subjects were treated concurrently (i.e., every monkey received the same treatment on a given day). The range of doses studied was: fenfluramine (1.0-10 mg/kg), methylphenidate (1.0-5.0 mg/kg), and diethylpropion (2.0-20 mg/kg). In general most drug/dose combinations produced decreases in social interactions. However, there was one notable exception; presenting was dramatically increased following dosing with methylphenidate and diethylpropion. Some of the solitary behaviors recorded were also observed to increase, notably, vocalization and self-grooming, which at the higher doses of diethylpropion and methylphenidate took the form of intensely idiosyncratic stereotypies. Finally, food consumption was observed to decrease in some subjects (more dominant) and increase in others (less dominant) indicating that social variables may interact with pharmacological variables.

Animals↗
PubMed1984

A comparison of the fenfluramine-induced serotonergic syndrome in rats subacutely treated with either saline or D-amphetamine.

The purpose of this study was to assess the activity of the serotonergic transmitter system in vivo in rats previously exposed to repeated injections of either saline or d-amphetamine. To do so, components of the serotonin syndrome, as induced by various doses of fenfluramine, were scored both before and after a 15-day subacute regimen with these agents. Fenfluramine caused hindlimb abduction, forepaw padding, and straub tail behaviors to be expressed in both groups of animals within 30 min after dosing; little or no activity with respect to these behaviors was seen in either regimen during the 30-60 or 60-90 min intervals. However, body-shaking behavior was consistently observed in both treatment groups during each observation period. No differences in the serotonergic syndrome as a whole or in the expression of each individual component of the syndrome (i.e., hindlimb abduction, straub-tail, forepaw padding, body shakes) were noted either between or within regimens before or after subacute saline or d-amphetamine treatment. Thus, the previously observed decrement in fenfluramine's food intake suppressant action, which resulted from subacute d-amphetamine treatment, is not likely to be due to gross alterations in the central serotonergic system.

Animals↗
PubMed1983

Delayed de novo methylation in teratocarcinoma suggests additional tissue-specific mechanisms for controlling gene expression.

Retrovirus infection of embryonal carcinoma cells is blocked at the level of provirus transcription. De novo methylation of the input provirus occurs in embryonal carcinoma cells but not in permissive, differentiated teratocarcinoma. The kinetics of proviral methylation in embryonal carcinoma cells, however, suggest that while methylation may have an important maintenance role in controlling gene expression, additional mechanisms are used by the early embryo to initiate negative gene expression.

Animals↗