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Biomedical subjects

M G King

Publications and source records attributed to M G King.

At least 19 recordsLinked to original sources
PubMed1992

Sleep deprivation-induced hyperthermia following antigen challenge due to opioid but not interleukin-1 involvement.

Eight hours total sleep deprivation does not affect colonic temperature. The combination of a subpyrogenic challenge of sheep red blood cells with sleep loss however, can produce a significant rise in colonic temperature that peaks during the third hour of the sleep deprivation vigil. The regulation of this increase in colonic temperature appears to be opioid in nature and not because of the release of the cytokine interleukin-1. It would appear that the combination of sleep loss and low dose antigen challenge, both manipulations of themselves nonpyrogenic, produces a synergistic rise in colonic temperature. The implication of a psychologically-derived stress response via the opioid system may explain this finding.

Animals↗
PubMed1992

Lithium chloride and immunomodulation in taste aversion conditioning.

Lithium chloride has been used in many studies of conditioning to induce taste aversion behaviour, and in some experiments investigating conditioning effects on immunity it has been used on the assumption that it is immunologically neutral. The studies reported here, however, indicate that LiCl is not immunologically neutral and when used to endow a UCS with noxious properties to enhance the behavioural response in taste aversion conditioned immunosuppression, it may antagonize the residual immunosuppression following initial UCS administration and also the conditioned immunosuppression occurring after CS reexposure. Therefore, conclusions drawn from studies of behaviourally conditioned immunomodulation where LiCl is used as part of either the CS or UCS may require reevaluation.

Animals↗
PubMed1991

Effect of paraformaldehyde fixation on localization and characterization of insulin-like growth factor-I (IGF-I) receptors in the rat brain.

In order to design an approach for localizing IGF-I receptors within the intact CNS, the effect of paraformaldehyde (PAF) fixation on receptor binding was examined. Cryostat sections of rat brains, which were perfused with 0 to 10% PAF, were incubated in 125I-IGF-I and assayed for binding under equilibrium conditions. Binding was quantified from 10 brain regions, involving laminae and nuclei from median eminence, thalamus, hippocampus, choroid plexus, pyriform cortex, and cerebral cortex, by computer densitometry of film autoradiographs. The specific binding, saturation curves, Bmax and Ka, ligand specificity, and binding reversibility of IGF-I binding sites were not significantly affected by 1% or 2% PAF. However, 4% PAF elevated IGF-I receptor total binding, nonspecific binding, and Ka, and decreased Bmax, presumably by increasing the number of tissue-receptor interconnections. Only nonspecific 125I-IGF-I binding persisted when 10% PAF was used. These results indicate that tissue perfused with 2% PAF can be used for localizing IGF-I receptors by autoradiographic binding methods.

Animals↗
PubMed1991

Modulation of body temperature through taste aversion conditioning.

Injection of rats with bacterial lipopolysaccharide (LPS) results in an initial fall in body temperature followed by a fever. Lithium chloride (LiCl) injection induces a fall in body temperature without subsequent fever production. When these substances were incorporated as unconditioned stimuli in a taste aversion conditioning paradigm, using saccharin flavour as the conditioning stimulus, these differential effects on body temperature were reenlisted on reexposure to saccharin alone 7 days after conditioning. The changes in body temperature on reexposure were similar in direction and kinetics as on the conditioning day although reduced in magnitude. The finding of a true conditioned effect in these studies is in contrast to the paradoxical or compensatory conditioned body temperature responses described elsewhere using different conditioning models. This apparent conflict may be explained on the basis of different unconditioned stimuli acting on efferent versus afferent arms of a negative feedback system. Since body temperature changes often occur in association with immune responses, these findings may have implications to behavioural conditioning of immunity, the outcome of which may reflect the indirect effects on immunity of inadvertent conditioning of thermoregulatory changes.

Animals↗
PubMed1991

Behavioral conditioning prolongs heart allograft survival in rats.

Conditioned immunosuppression using a taste aversion paradigm has been demonstrated in a number of laboratory models but few reports have demonstrated changes in immunity sufficient to be of clinical relevance. The experiments reported here demonstrate that the survival of heart allografts in rats can be prolonged by behaviorally conditioned immunosuppression using cyclosporin A (CsA) as an unconditioned stimulus in taste aversion conditioning. Conditioned animals received saccharin as the conditioned stimulus paired with an injection of CsA at 10 and 6 days prior to transplantation. They were reexposed to saccharin alone 1 day prior to and 3 days after transplantation. On these occasions the conditioned group displayed taste aversion behavior when offered saccharin and a significant prolongation of heart graft survival was observed compared to the conditioned and nonconditioned control groups. These experiments suggest that behaviorally conditioned immunosuppression may have important clinical implications as an adjunct to drug treatments in transplantation medicine.

Abdomen↗
PubMed1990

Are antibiotic effects on sleep behavior in the rat due to modulation of gut bacteria?

The sleep-inducing substance Factor S (FS) is unique among candidate sleep molecules because of its bacterial origin. FS is derived from the bacterial cell wall and accumulates in the brain and body fluids of sleep-deprived animals including man. Exogenous administration of FS and related muramyl peptides results in an increase in slow-wave sleep (SWS). To test the possibility that gastrointestinal bacteria are a source of FS, rats were placed on an antibiotic regimen (neomycin and metronidazole in drinking water) and sleep measures taken after one week. There was a significant reduction in SWS in the first three hours of the lights-on period as well as an increase in sleep latency. No other sleep parameters, including Rapid Eye Movement (REM) sleep measures, were affected, suggesting that there was a specific SWS effect due to bacterial reduction. Possible toxic effects of the antibiotic treatment were unlikely factors in SWS reduction due to the stability of other sleep measures such as number of episodes of SWS and REM, total sleep time and REM latency. Oral administration of live E. coli to rats did not affect any sleep measures. It appears that FS may be specifically involved in the early sleep period where it promotes sleep onset and SWS generation.

Animals↗
PubMed1990

The influence of dexamethasone on behaviorally conditioned immunomodulation and plasma corticosterone.

Utilizing a conditioned taste aversion paradigm we have previously shown that rats re-exposed to a saccharin solution previously paired with cyclophosphamide (CY) demonstrate significantly reduced in vitro mitogen-induced spleen cell proliferation and IgM secretion assessed 24 h after saccharin re-exposure. In this report treatment of similarly conditioned rats with dexamethasone (DEX) either before conditioning or before re-exposure abrogated the conditioned modulation of pokeweed mitogen (PWM)-induced spleen cell proliferation. The finding that DEX pretreatment on the conditioning day was as effective in abrogating the conditioned response as DEX treatment prior to the test day does not support pituitary-adrenal mediation of the conditioned immusuppressive effect following re-exposure of conditioned animals to the CS. There was no significant conditioned immunosuppression observed with respect to PHA- and Con A-induced proliferation and the influence of DEX on these parameters could not be assessed. The effect on PWM-induced IgM production was inconclusive since the reduced IgM response among conditioned animals was of only borderline significance.

Animals↗
PubMed1989

Immunomodulation by behavioural conditioning.

The contemporary surge in studies of behaviourally conditioned immunomodulation following Ader and Cohen (1975) was preceded by Pavlovian conditioning conducted in the Soviet Union during the 1920s and 1950s. Data from these studies provided a tenable hypothesis for immunomodification using classical conditioning processes. In particular a variant of Pavlovian conditioning, the conditioned taste aversion (CTA) paradigm, has proved very robust; here a novel gustatory experience (CS) is paired with an aversive physiological event (UCS) and subsequent gustatory avoidance of the CS alone is measured. Similar procedures have also been successfully applied to the conditioned alteration of cellular immune responses. Studies demonstrating behaviourally conditioned effects on the immune system are reviewed. More recently, conditioned immunoenhancement studies have demonstrated that taste aversion can induce a conditioned increase in the helper: suppressor T cell subset ratio in rats, and a depressed DTH response in mice. Mediating mechanisms for the conditioned effects are examined, in particular the roles of adrenocorticotropin (ACTH) and beta-endorphin (BEP), and the routes of communication between the CNS and immune system. Clinical applications of immunomodification may also be demonstrated by the potential therapeutic efficacy of both conditioned immunosuppression and immunoenhancement.

Animals↗
PubMed1989

Interleukin-1 beta and muramyl dipeptide can prevent decreased antibody response associated with sleep deprivation.

A single, brief (8 h) period of sleep deprivation (DEP) was found to suppress secondary antibody response to sheep red blood cells in rats. This decrease could be totally prevented if either interleukin-1 beta (IL-1) or muramyl dipeptide (MDP) was administered at the beginning of the DEP vigil. Twenty-five units of IL-1 or 250 micrograms/kg MDP was found to be immunosuppressive in sleeping rats but, paradoxically, the combination of such doses with DEP alleviated this effect. Increased colonic temperatures associated with antigen and/or adjuvant administration were not related to the differences in antibody levels between sleeping and DEP animals. Activation of hypothalamic dopamine in IL-1-treated rats following DEP suggests that this monoamine transmitter system may participate in the observed protective activity of IL-1. The present findings extend the immune adjuvant effects of both IL-1 and MDP to protection of the host against behaviorally induced immunosuppression.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Nursing shortage, circa 1915.

Nursing shortages have plagued the occupation from its infancy. Analysis of works by M. Adelaide Nutting and Isabel Stewart reveals factors that early leaders identified as concerns or causes of past shortages. Although both Stewart and Nutting identified serious problems in the nature of nursing work, both recommended improvements in nursing's educational programs along with publicity campaigns as possible solutions. A case study of the Peter Bent Brigham School in Boston suggests that early leaders focussed on these strategies for change because the position of nursing in the hospital left them powerless to initiate meaningful change in the nature of nursing work.

Boston↗
PubMed1989

Localization and structural characterization of insulin-like growth factor receptors in mammalian retina.

Insulin-like growth factors (IGFs) are peptide mitogens, structurally related to insulin, whose biological actions in the CNS are incompletely known. The retina is largely uncharacterized with respect to IGF receptors. We, therefore, studied IGF receptors in bovine and murine retinal tissues by immunohistochemistry, autoradiographic localization, and affinity labeling. Notable IGF-II receptor immunoreactivity was found in retinal pigment epithelium (RPE), with intermediate levels in choroid, low levels in the inner and outer plexiform layers and outer nuclear layer, and very low levels in other regions. Autoradiographic localization using [125I]IGF-II confirmed the IGF-II receptor immunohistochemistry. Autoradiographic localization using [125I]IGF-I labeled the nuclear layers and the photoreceptor region. Affinity labeling disclosed differences in the apparent mol wt of IGF-I and IGF-II receptors from bovine eye tissues and those from liver and brain. IGF-I receptor alpha-subunits (the IGF-binding subunit) migrated at: liver, 139,000; brain, 125,000; RPE, 125,000 and 135,000 (two sizes); and retina, 125,000 and 135,000. IGF-II receptors migrated at: liver, 245,000; brain, 235,000; RPE, 240,000; and retina, 230,000. We conclude that mammalian retina contains both IGF-I and -II receptors, which differ from those found in other tissues and have a characteristic spatial distribution within the retina.

Animals↗
PubMed1988

Autochthonous intestinal bacteria and coprophagy: a possible contribution to the ontogeny and rhythmicity of slow wave sleep in mammals.

A sleep-inducing substance Factor S (FS) has been identified as a member of the muramyl peptide family of molecules which constitute the cell wall of bacteria. FS-like substances are unable to be synthesized by mammals suggesting that the symbiotic bacteria of the gastrointestinal tract are a prime source of FS. The present paper considers the relationship between the ontogenesis of Slow Wave Sleep (SWS) and the colonization of the intestine with strictly anaerobic bacteria. The practice of coprophagy in rats and rabbits is considered as an efficient method of FS ingestion during the sleep period.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Behaviorally conditioned suppression of mitogen-induced proliferation and immunoglobulin production: effect of time span between conditioning and reexposure to the conditioning stimulus.

Rats were subjected to taste aversion conditioning using the immunosuppressive drug cyclophosphamide (CY) as the unconditioned stimulus (UCS) paired with saccharin, the conditioned stimulus (CS), and were reexposed to the CS at 2, 5, or 10 days after a single conditioning trial. Twenty-four hours after reexposure the rats were sacrificed and spleen cells assayed for mitogen-induced proliferation and immunoglobulin production. A robust conditioned taste aversion (CTA) was observed irrespective of the day of CS reexposure. However, only conditioned rats reexposed to the CS 2 days after training displayed a conditioned reduction in proliferative responses to PHA and PWM. These rats also exhibited a reduction in the synthesis of IgM, but not IgG or IgA, by spleen cells cultured with PWM. These effects were not observed in conditioned rats reexposed 5 or 10 days after conditioning. In another experiment, rats were subjected to a backward conditioning (UCS prior to CS) training trial, tested 2 days later for the presence of CTA, and sacrificed 24 h later for assessment of immune function as described above. The results of this experiment demonstrated that rats do not develop an aversion to saccharin when it is first presented 4 h after CY, and no alterations in spleen cell proliferation and immunoglobulin production were noted. The data show that the CTA response established by explicit association between CY and saccharin depresses in vitro spleen cell proliferation and IgM production only when elicited shortly after the conditioning trial.

Animals↗
PubMed1987

Synergism of a compound unconditioned stimulus in taste aversion conditioning.

Anti-lymphocyte serum (ALS) and lithium chloride have both previously been used successfully as unconditioned stimuli in taste aversion conditioning paradigms in rats. This report substantiates those findings but shows that when the two stimuli are given as a compound unconditioned stimulus in association with saccharin flavoured drinking solution, the conditioned taste aversion response following a second exposure to saccharin alone is more profound than that following conditioning with either ALS or LiCl alone. These results demonstrate synergism between the two stimuli when given together.

Animals↗
PubMed1987

Behaviourally conditioned modification of T cell subset ratios in rats.

Levamisole injection resulted in an elevation in the T helper:T suppressor (H:S) subset ratio in rats at 24 h after injection due to a selective depression in the cytotoxic/suppressor subset. This response was shown to be conditionable and could be reenlisted 14 days later by re-exposure to the conditioned stimulus. Rats were conditioned using a taste aversion paradigm by pairing levamisole injection with the novel taste of saccharin. Fourteen days later, after a second exposure to saccharin without levamisole injection, H:S ratios were elevated in the blood of these rats compared to control rats injected with levamisole but fed normal water or rats fed saccharin without levamisole injection.

Adjuvants, Immunologic↗
PubMed1987

In vivo effects of beta-endorphin on lymphocyte proliferation and interleukin 2 production.

Experiments were undertaken in rats to investigate the effects of in vivo infusion of beta-endorphin (BEP) on subsequent Con A-induced proliferation and interleukin 2 (IL-2) production by spleen cells in vitro. BEP administration induced a dose-dependent enhancement of the proliferative response to Con A. Infusion of the opiate antagonist naloxone (NAL) inhibited the Con A response and infusion of NAL prior to BEP resulted in even further inhibition. None of these treatments resulted in detectable alterations in IL-2 production after 48 h in culture. To demonstrate a direct interaction between BEP and lymphocytes, spleen cells were incubated in vitro with varying concentrations of BEP and/or NAL. Enhanced Con A-induced proliferation was observed following incubation with BEP in the range 10(-12) to 10(-9) M (levels comparable to the effective in vivo doses) and this effect was abrogated by NAL pretreatment (10(-6) M). These data indicate a role for BEP in enhancing lymphocyte reactivity which is to some extent dependent on opiate receptors on the cell surface. This report extends the evidence obtained from in vitro experiments implicating endogenous opioids in modulation of host immunity by demonstrating that these effects can be obtained in vivo.

Animals↗