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Biomedical subjects

B M Bayer

Publications and source records attributed to B M Bayer.

At least 37 records · Page 2Linked to original sources
PubMed1993

Increases of CCK mRNA and peptide in different brain areas following acute and chronic administration of morphine.

The present study examined whether either acute or chronic administration of morphine resulted in changes in the content of CCK mRNA and CCK immunoactive peptide in selective areas of the rat brain and spinal cord. Two hours after a single injection of morphine (10 mg/kg, s.c.), CCK mRNA significantly increased in the hypothalamus (0.8-fold) and spinal cord (2-fold) relative to the CCK mRNA content in saline-injected controls. No significant differences in CCK mRNA were observed in the frontal cortex, hippocampus, midbrain or brainstem. There were no significant alterations in CCK immunoreactivity in any brain regions and spinal cord after the acute treatment with morphine. Upon repeated morphine administration, the content of CCK mRNA in both the hypothalamus and the spinal cord was further elevated by at least 3-fold. A significant increase of CCK mRNA content in brain stem (2.8-fold) was also observed following chronic morphine administration. In contrast to the acute exposure to morphine, chronic administration resulted in significant increases in CCK immunoactive peptide in hypothalamus (2.6-fold), spinal cord (2.1-fold) and brainstem (1.6-fold), but not in the other brain areas. These results demonstrate that morphine, especially following repeated administrations, stimulates endogenous CCK biosynthesis in selective brain regions.

Analgesics↗
PubMed1993

Immunosuppression by morphine is mediated by central pathways.

We reported previously that a single systemic injection of morphine (10 mg/kg) to rats profoundly suppressed mitogen-induced proliferation of blood lymphocytes by a receptor-mediated mechanism. The present study examined whether this immunosuppressive effect of morphine is mediated by opioid receptors located at either peripheral or central sites. First, the effects of systemic morphine administration on analgesia, mitogen-stimulated lymphocyte proliferation and corticosterone secretion were compared to those observed after the systemic administration of N-methylmorphine, a quaternary derivative which does not readily penetrate the blood-brain barrier. In contrast to systemically administered morphine, the i.p. injection of N-methyl-morphine (20 mg/kg) was without any effect on lymphocyte proliferation, plasma corticosterone concentrations or analgesic responses. Secondly, the effects of morphine and N-methylmorphine after central administration were compared. Within 2 hr after the microinjection of either morphine (10 micrograms/2 microliters) or N-methylmorphine (15 micrograms/2 microliters) into the third ventricle, blood lymphocyte responses were inhibited by 70%, plasma corticosterone concentrations were significantly elevated and maximal analgesic responses were present. Finally, microinjection of morphine (1 microgram/0.2 microliter) into the anterior hypothalamus inhibited blood lymphocyte proliferation by 50% without producing analgesia or a significant increase in plasma corticosterone. These findings suggest that central opioid pathways are involved in the immunosuppressive effects of morphine and these pathways may be distinct from those participating in opioid-induced analgesia and adrenal activation.

Animals↗
PubMed1990

Changes in T and B lymphocyte proliferative responses in adjuvant-arthritic rats: antagonism by indomethacin.

The effects of a potent non-steroidal antiinflammatory drug, indomethacin, on the inflammatory response and lymphocyte proliferation were investigated in adjuvant-arthritic rats. As shown by others, adjuvant produced a time-dependent swelling of the contralateral paw which was maximal within 14 days after administration. Upon the intraperitoneal injection of either 1 or 2 mg/kg of indomethacin, twice daily for 3 days, the swelling of the contralateral paw was completely reduced. Selective changes in proliferative responses of splenic T and B lymphocytes to mitogens were found to accompany these effects. Adjuvant arthritic rats were found to have increased T cell proliferation when stimulated with phytohemagglutinin, whereas proliferation of B lymphocytes in the presence of lipopolysaccharide was completely suppressed. Indomethacin treatment at either the 1 or 2 mg/kg dose was found to depress the proliferative responses of T cells by 60 and 95%, respectively. In contrast, the hyporesponsiveness of B lymphocytes in arthritic animals was partially reversed with 2 mg/kg indomethacin. These results suggest that indomethacin may be exerting an antiinflammatory effect through a selective alteration of T and B lymphocyte activities in lymphoid tissue.

Animals↗
PubMed1990

Morphine inhibition of lymphocyte activity is mediated by an opioid dependent mechanism.

The effects of acutely-administered morphine on mitogen stimulated lymphocyte proliferation and natural killer cell cytolytic activity were investigated. Two hours after a subcutaneous injection of morphine (25 mg/kg), blood lymphocyte proliferation was found to be 70% depressed, compared to saline-injected controls. This effect was partially antagonized in animals pretreated with naltrexone (10 mg/kg) and was present only in blood lymphocytes, since proliferative responses of splenic lymphocytes were not significantly altered. The administration of morphine, however, did result in a 30-40% inhibition of cytolytic activity of natural killer cells, which was completely antagonized in naltrexone-pretreated animals. Naltrexone alone was found to have no effect on either proliferation of blood and splenic lymphocytes or the cytolytic activity of splenic lymphocytes. Although naltrexone had no effect on the activity of lymphocytes, animals treated with either naltrexone or morphine alone, or their combination, had 4- to 8-fold increases in corticosterone in plasma. These results demonstrate that the effect of morphine on immune cells was dependent on the tissue source of lymphocytes. Furthermore, the suppression of blood lymphocyte proliferation and splenic cytolytic activity of natural killer cells by morphine was opiate receptor-mediated, as indicated by the reversibility by naltrexone of the observed effects of morphine. Finally, the accompanying increase in circulating levels of corticosterone most likely did not contribute to these effects.

Animals↗
PubMed1990

Restraint stress-induced elevations in plasma corticosterone and beta-endorphin are not accompanied by alterations in immune function.

A variety of stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, thereby resulting in elevated levels of circulating ACTH, beta-endorphin and corticosterone. Since these hormones have been shown previously to alter measures of immune function, we determined whether presentation of a stressor which activates the HPA axis produces a concomitant alteration in immune function. Restraint stress resulted in significantly elevated levels of corticosterone and beta-endorphin without affecting either proliferative or cytolytic activities of lymphocytes. At concentrations similar to those achieved during stress, in vivo, corticosterone exhibited a dose- and time-dependent reduction in both lymphocyte proliferation as well as natural killer cytotoxicity, in vitro. beta-Endorphin, on the other hand, was without direct or modulatory effects. These results indicate that restraint stress-induced activation of the HPA axis occurs without accompanying alterations in immune function.

Animals↗
PubMed1989

Time-dependent effects of isolation on lymphocyte and adrenocortical activity.

Individual housing of previously group-housed animals was found to result in time-dependent changes in mitogen-induced lymphocyte proliferation and plasma corticosterone concentrations. During the first week of isolation, both B and T lymphocyte responses were depressed. However, within 2 weeks at least a 2-fold enhancement was observed. The increased lymphocyte response was still present after 35 days of isolation. Within the first day of isolation and continuing for 2 weeks, plasma corticosterone levels were found to be significantly decreased in isolated animals compared to those of continuously housed animals. No significant differences in steroid levels were observed by 35 days. These data demonstrate that isolation is accompanied by a depressed adrenocortical activity and suggest that the immunosuppression associated with short-term exposure is mediated by factors other than corticosterone.

Adrenal Cortex↗
PubMed1988

Time-dependent enhancement of lymphocyte activation by mitogens after exposure to isolation or water scheduling.

The effects of isolation and water scheduling on mitogen induced lymphocyte proliferation were investigated. Isolated rats were animals which had been raised in group-housed conditions and then transferred to individual cages with ad lib access to water for a 1 or 2 week period. Water scheduled rats were maintained in group housing (5 rats per cage) with ad lib access to food but with access to water for a single 30 minute session each day. Responses of these groups were compared to those of animals which had been continuously group-housed with ad lib access to food and water. No differences in lymphocyte responses to phytohemagglutinin (PHA) were found 1 week after exposure to isolation. However, after 2 weeks, splenic and blood T lymphocytes from isolated animals demonstrated an increased proliferative response to suboptimum and maximum concentrations of PHA. Splenic B lymphocyte responses to lipopolysaccharide (LPS) from isolated animals were also increased by 2- to 3-fold compared to group-housed controls. Two weeks of exposure of animals to daily water scheduling similarly increased the splenic lymphocyte proliferation. This increased responsiveness to PHA was not accompanied by a significant change in the sensitivity of the lymphocytes to PHA, in the total number of white blood cells, or the proportion of splenic T or T helper lymphocytes. Our results show that the increase in lymphocyte proliferation is time-dependent, requires greater than 1 week of exposure to isolation and is due to factors other than changes in sensitivity to mitogen or T lymphocyte number.

Animals↗
PubMed1987

In vitro and in vivo effects of indomethacin on phytohemagglutinin-stimulated lymphocyte mitogenesis.

The in vitro and in vivo effects of indomethacin on blastogenesis of rat splenic lymphocytes in response to phytohemagglutinin (PHA) were investigated. Direct addition of indomethacin to lymphocyte cultures was found to have both a stimulatory effect at low concentrations (less than or equal to 0.003 microM) and an inhibitory effect at higher concentrations (greater than or equal to 0.01 microM). The in vitro stimulation was significant only at submaximal and supramaximal concentrations of PHA, whereas the inhibitory response was observed with a wide range of mitogen concentrations. When indomethacin was administered to animals twice daily for 3 days, similar dose-dependent stimulatory and inhibitory effects were observed. Again the stimulatory effects were associated with lower doses (0.1 microgram/kg) and were found to be significant only with submaximal PHA concentrations. The inhibition with higher doses of indomethacin (IC50 = 0.20 mg/kg) was accompanied by a dose-dependent decrease in the maximal response and an increase in the EC50 to PHA in indomethacin-treated animals. These inhibitory effects of indomethacin administration on lymphocyte proliferation were found to occur at doses which closely approximate those required for the anti-inflammatory effects of the drug.

Animals↗
PubMed1987

Enhancement of rat lymphocyte proliferation after prolonged exposure to stress.

Rats exposed to 5 weeks of isolation, water scheduling (daily consumption restricted to 30 min), and their combination demonstrated significantly enhanced splenic lymphocyte proliferative responses to phytohemagglutinin (PHA) compared to those of group-housed animals (five per cage) maintained under standard vivarium conditions. The increased response found with the combination treatment was of the same magnitude as that found with each stressor alone. Blood lymphocyte responses were similarly increased after 5 weeks of isolation. When animals were exposed to the combination treatment for 12 weeks, both blood and splenic lymphocyte responses were found to be enhanced by greater than 2- and 3-fold, respectively. At the time of sacrifice no changes were found in total white blood cell numbers or plasma corticosterone levels with any of these treatments. These data suggest that prolonged exposure to a stressor results in an enhancement of immune cell activity.

Animals↗
PubMed1986

Inhibition of amino acid transport by nonsteroidal anti-inflammatory drugs: a model for predicting relative therapeutic potency.

Indomethacin has been shown to inhibit selectively the rate of alpha-(methylamino)-isobutyric acid (MeAIB) uptake by the "A" transport system in several cell types. This study was undertaken to determine if this activity was shared by other nonsteroidal anti-inflammatory drugs (NSAID), if the inhibition of MeAIB transport was unique to drugs with anti-inflammatory activity and finally if it could be correlated with their in vivo potency in humans and in animal test systems. Utilizing BRLT rat hepatocyte cultures (hepatocytes cloned from Buffalo rats); it was found that all of the acidic NSAID tested inhibited MeAIB uptake in a dose-dependent manner with IC50 values in the low to midmicromolar range. The amount of inhibition was dependent on cell density, time of incubation with drug, the media pH and its concentration of protein and amino acids. The order of potency of the acidic NSAID in inhibiting MeAIB uptake was found to be correlated closely with their potency in the inhibition of prostaglandin synthesis in vitro, the suppression of induced inflammatory reactions in rats and the maximum recommended daily doses in humans. Pharmacologically inactive metabolites of several NSAID had little or no effect on MeAIB transport at concentrations up to 10 times greater than active parent compounds. Other compounds tested, including glucocorticoids, were found to have little effect on the rate of MeAIB uptake. These studies indicate that the inhibition of MeAIB uptake in BRLT cells may represent a reliable and rapid screen for predicting the therapeutic potency of newly developed NSAID.

Adrenal Cortex Hormones↗
PubMed1985

The PD subscales: an empirical evaluation.

Harris and Lingoes' (1955) six PD subscales were assessed empirically for their convergent validity and for their utility to discriminate amongst male offenders on the two outcome measures of successful completion of sentences at a correctional halfway house and reincarceration at a 1-year follow-up. The results provided varying degrees of convergent validity for the six constructs devised by Harris and Lingoes. In addition, four of the six subscales predicted success in the halfway house program; one of the six subscales predicted reincarceration. The results were viewed with respect to the overall validity of the PD subscales and with respect to the utility of the subscales to guide dispositions with regard to the placement of offenders into halfway houses.

Adolescent↗
PubMed1981

Inhibition of the expression of the "A" system of amino acid transport by anti-inflammatory drugs during cell culture growth and mitogenic stimulation of thymus lymphocytes.

alpha-Methylaminoisobutyric acid uptake is mediated by two components in a variety of cell culture lines as well as in freshly isolated thymus lymphocytes. In all cell types, one component of uptake had characteristics similar to that of the "A" system and was selectively inhibited by the nonsteroidal anti-inflammatory drugs. Detailed studies with indomethacin showed that, in the presence of drug, a marked decrease in Vmax occurred with no impairment in the apparent affinity (Km) of the uptake system for either the amino acid or Na+ ion. Upon removal of drug, the capacity (Vmax) of the cell lines to take up amino acid recovered over the course of 6 hr. It is postulated that this time course may be related to a change in the number of functional carriers in the cell membrane. Marked increases in the rate of alpha-methylaminoisobutyric acid uptake by the Na+-dependent component were observed during exponential growth of cell cultures and in thymus lymphocytes stimulated by concanavalin A or amino acid deprivation. Irrespective of the cell type or mechanism of stimulation, indomethacin either blocked or partially suppressed this increase. Suppression of the Na+-dependent component of alpha-methylaminoisobutyric acid uptake was also evident in lymphocytes from indomethacin-treated rats. Selective inhibition of the A system before DNA synthesis may be one mechanism by which the anti-inflammatory drugs exert their in vitro cytostatic and in vivo immunosuppressive action

Amino Acids↗
PubMed1980

Anti-inflammatory drugs alter amino acid transport in HTC cells.

Following the addition of indomethacin to exponentially growing rat hepatoma cell (HTC) cultures, cells accumulated in the G1 phase. Over the course of several hours, specific changes in membrane transport accompanied this inhibition. Indomethacin stimulated the uptake of 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH), inhibited the Na+-dependent active transport of alpha-aminoisobutyric acid (AIB), and methylaminoisobutyric acid (MeAIB), but had no effect on the uptake of thymidine, uridine, or 2-deoxyglucose. The stimulation of BCH transport was immediate and reversible. The uptake of BCH was Na+-independent and only slightly depressed by metabolic inhibitors (10 to 20%). Inhibition of AIB and MeAIB uptake, which was of gradual onset, and was observed with several anti-inflammatory drugs and was dependent on the concentration of drugs. Upon removal of drug, AIB and MeAIB transport gradually increased and reached a maximum prior to resumption of DNA synthesis and cell division. Thee effects involved changes in Vmax only. Neither the apparent affinity (Km) for amino acids nor rate of exodus (k, 0.7h-1 for BCH, 1.2h-1 for AIB) were altered. The uptake of MeAIB (and AIB) occurred by a low and a high affinity (Km = 0.27 mM) component. Indomethacin inhibited specifically the high affinity component which was shown to be Na+- and energy-dependent. Although this component was inhibited by treatment with agents that lowered ATP levels or blocked protein synthesis, the anti-inflammatory drugs appeared not to act through these mechanisms.

Amino Acids↗
PubMed1980

Evidence that histamine does not participate in carrageenan-induced pleurisy in rat.

The injection of carrageenan into the rat pleural cavity provoked an intense inflammatory reaction with the formation of an exudate which contained mainly neutrophils but which was also rich in mast cells and histamine. There was, however, no evidence that histamine participated in the reaction. The mast cells remained intact, and no increase in extracellular histamine levels was observed. Prior treatment with bot H1 and H2 histimine receptor antagonists or depletion of the histamine stores by pretreatment with compound 48/80 did not alter the reaction. In contrast, the exudate formed in response to the intrapleural injection of small doses (0.05 mg/kg) of compound 48/80 was reduced by pretreatment with the antihistamine compounds and, unlike the exudate formed after carrageenan injection, was devoid of neutrophils. Since saline washes of the pleural cavity of untreated rats had histamine and mast cell contents similar to those of the exudates of the carrageenan-treated rats, the source of histamine appeared to be mast cells from the pleural cavity.

Animals↗