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M Lyte

Publications and source records attributed to M Lyte.

At least 37 records · Page 2Linked to original sources

Effects of in vitro adrenocorticotrophic hormone, cortisol and human recombinant interleukin-2 on porcine neutrophil migration and luminol-dependent chemiluminescence.

Experiments were performed on isolated neutrophils tested in vitro to investigate the role of adrenocorticotrophic hormone (ACTH), cortisol and recombinant human interleukin-2 (rhIL-2) in modulating porcine polymorphonuclear (PMN) leukocyte function. Elevated levels of cortisol, similar to that observed during stressful experiences, caused a decrease in PMN chemokinesis (P < 0.02), chemotaxis (P < 0.001) and luminol-dependent chemiluminescence. ACTH at concentrations reflective of high stress conditions reduced PMN chemotaxis (P < 0.02) and chemokinesis (P < 0.01). In vitro rhIL-2 reversed (P < 0.05) the cortisol-induced and ACTH-induced suppression of PMN chemokinesis. These data indicate that specific neutrophil functions in pigs may be impaired by stress-related hormones of the pituitary-adrenal axis and that IL-2 may reverse some endocrine-induced suppression in chemokinesis.

Adrenocorticotropic Hormone↗

Catecholamine induced growth of gram negative bacteria.

The addition of various catecholamines to cultures of gram negative bacteria resulted in dramatic increases in growth. The ability of norepinephrine, epinephrine, dopamine and dopa to enhance the growth of Escherichia coli, Yersinia enterocolitica and Pseudomonas aeruginosa was observed to be dependent on the bacterium employed with each strain showing marked preference for one or more of the catecholamines. Catecholamine induced increases in growth were confirmed by one or more of the following methods: uptake of tritiated thymidine into newly synthesized DNA, changes in optical density or pour plate analysis. None of the catecholamine metabolites resulting from either oxidative deamination or catechol-O-methylation were able to effect similar increases in bacterial growth as compared to either norepinephrine, epinephrine or dopamine. Norepinephrine was consistently observed to effect the greatest increase in bacterial growth for all strains tested.

Catecholamines↗

The role of catecholamines in gram-negative sepsis.

Recently obtained in vitro evidence has demonstrated that neurochemicals such as the catecholamines can dramatically increase the growth of Gram-negative bacteria. Depending on the catecholamine, an up to 100,000-fold increase in the in vitro growth rate of pathogenic Gram-negative bacteria such as Escherichia coli and Yersinia enterocolitica can be observed. Dramatic elevations in the levels of plasma catecholamines have been amply demonstrated to occur as part of the neurophysiological response to infection. It is proposed that the ability of pathogenic bacteria to utilize the host's neurophysiological response to infection to modulate its own growth may govern the eventual clinical outcome of the infection.

Bacteremia↗

Effects of in vitro electrical stimulation on enhancement and suppression of malignant lymphoma cell proliferation.

The suppression and enhancement of proliferation of mouse EL4 lymphoma cells varied significantly when the cells were electrically stimulated within a narrow range of low-level direct current. With the use of platinum electrodes, the suppression characteristics were observed over a narrow range, or window, of direct currents centered at approximately 17 microA. Enhancement characteristics were observed over a broad range of low-level direct currents (approximately 0.1 to 10 microA). These results indicate that the proliferation of certain eukaryotic cells may be directly controlled by stimulation with low-level direct current.

Animals↗

Strain-specific enhancement of splenic T cell mitogenesis and macrophage phagocytosis following peripheral axotomy.

The inbred mouse strains C57BL/6 and DBA/2 were subjected to the selective depletion of peripheral nervous system norepinephrine (NE) by the administration of the neurotoxin 6-hydroxydopamine (6-OH-DA). Measurement of mitogen-induced lymphocyte proliferation following peripheral axotomy with 6-OH-DA revealed that significant enhancement (up to 200% of control values) of T, but not B, cell proliferative responses occurred in DBA/2, while no effect was observed in C57BL/6. Enhancement (up to 196% of control values) of luminol-enhanced chemiluminescence resulting from the phagocytosis of opsonized zymosan was also observed following 6-OH-DA treatment in DBA/2, but not C57BL/6. This strain-specific enhancement of immune responses occurred even though the administration of 6-OH-DA resulted in a similar depletion of splenic NE content (greater than 97% reduction of control values) in both strains as determined by high-pressure liquid chromatography-electrochemical detection. Blockage of the neurotoxic effects of 6-OH-DA was achieved by the use of the catecholamine uptake blocker desipramine-HCl. Administration of desipramine prior to 6-OH-DA blocked the reduction of splenic NE content and abrogated the enhancement of mitogen-induced T cell proliferation. The enhancement of phagocytosis by 6-OH-DA was not, however, altered by the prior administration of desipramine.

Animals↗

Identification, location and analysis of contamination problems associated with cell/tissue preparation, stimulation and measurement techniques.

Any time a cell suspension or tissue sample is handled, chemically treated and prepared or measured with electrical or electrochemical probes, some level of contamination will occur. Often, the level and type of contamination can lead to serious misinterpretation of experimental results. A number of specific contamination problems have been consistently observed with certain preparation, stimulation and measurement techniques utilized in cell biology, histology, microbiology and pharmacology. Four of the more serious problems that can occur are as follows: 1) contamination from media constituents; 2) contamination of cell suspensions and tissue from constituents and impurities in glassware; 3) fungal contamination of cell and tissue samples from glutaraldehyde fixatives and 4) contamination of cell suspensions and tissues from metal ions that have dissociated from electrodes and probes. A scanning electron microscope/energy dispersive x-ray (SEM/EDX) system can provide the resolution, sensitivity and analytical capability to detect these contaminants in a variety of locations, identify them and determine their origin. Thus, erroneous conclusions from data that have been affected by various contaminants can be minimized or prevented if the problems are identified and located.

Biological Assay↗

Examination of the neuroendocrine basis for the social conflict-induced enhancement of immunity in mice.

Intruder DBA/2 and C57BL/6 mice, which display different neuroendocrine responses to social conflict, evidence a pronounced increase in splenocyte phagocytosis of opsonized zymosan particles as a consequence of social conflict-induced stress. Interruption of the hypothalamic-pituitary-adrenal axis prior to social conflict results in an abrogation of the stress-induced enhancement of phagocytosis in DBA/2, but not in C57BL/6, mice. Administration of the opiate antagonists naloxone and naltrexone resulted in a potentiation of the stress-induced enhancement of phagocytosis in both strains. Similarly, administration of the alkylating antagonist beta-chlornaltrexamine which irreversibly blocks opioid binding sites potentiated the immune-enhancing effects of social conflict stress. Mitogen-induced T and B lymphocyte proliferation was unaffected by any of the experimental procedures with the exception of beta-chlornaltrexamine which suppressed activity equally in stressed and nonstressed groups. These results demonstrate the necessity of employing inbred murine strains in the dissection of the neuroendocrine pathways which govern stress-induced modulation of the immune system.

Aggression↗

Innate and adaptive immune responses in a social conflict paradigm.

Social conflict stress was examined for its effects on in vitro and in vivo immunity in mice. Adaptive immunity, as measured by the generation of primary IgM antibody responses to the T-dependent antigen keyhold limpet hemocyanin, was suppressed following chronic (greater than 1 day), but not acute (less than 1 day), stress periods while the IgM response to the T-independent antigen polyvinylpyrrolidone was not affected. In vitro proliferative responses of splenocytes to the T cell mitogen concanavalin A and the B cell mitogen lipopolysaccharide were unaffected. Acute (less than 1 day) stress dramatically increased innate immunity as measured by a luminol-dependent chemiluminescence assay of phagocytic cell function. DBA/2J mice averaged a 269% increase in phagocytosis as compared to a 412% increase in C57BL/6J. This differential effect of stress on immune responsiveness indicates that alterations in innate immunity in addition to adaptive immunity should also be considered when evaluating neuroendocrine and immune interactions in response to stress.

Animals↗

Modulation of human lymphocyte mitogen responsiveness and interleukin-2 production by polymorphonuclear leukocytes.

The response of human peripheral blood lymphocytes to the mitogenic lectins phytohemagglutinin (PHA) and pokeweed mitogen (PWM) was examined in the presence of autologous polymorphonuclear leukocytes (PMN). Experiments were performed at sub-optimal and optimal mitogen concentrations employing lymphocyte: PMN ratios over a three log cell concentration range. Increases of up to 25,000-fold in mitogen stimulated lymphocyte proliferation as determined by 3H-thymidine incorporation were observed in PMN supplemented lymphocyte cultures as compared to lymphocytes cultured in the absence of PMN or with irradiated lymphocytes serving as filler cells. Similar results were obtained for PHA stimulated IL-2 production. The degree of enhancement of lymphocyte reactivity by PMN was also shown to be dependent on the source of serum supplementation (autologous versus xenogeneic). These results indicate that cell ratio is a critical factor in examining lymphocyte-PMN interactions as well as serum supplementation used. Early reports which have indicated a suppressive or no effect of PMN on lymphocyte reactivity based on a single lymphocyte: PMN cell ratio may need to be re-evaluated.

Adult↗

In vitro production of interleukin-2 by lymphocytes in whole blood and isolated culture.

Interleukin-2 (IL-2) production was examined in mitogen stimulated human lymphocytes. Whole blood unseparated lymphocytes or Ficoll-Hypaque gradient purified lymphocytes were cultured. Lymphocytes in whole blood culture produced significantly greater amounts of IL-2 on a per cell basis than did Ficoll-Hypaque purified lymphocytes. Furthermore, the majority of IL-2 produced by lymphocytes in whole blood culture was shown by freeze-thaw lysis to be intracellularly located, while the majority of IL-2 produced by purified lymphocytes was detected extracellularly. The addition of 2-mercaptoethanol (2-ME) resulted in enhanced extracellular production of IL-2 in whole blood and Ficoll-Hypaque cultures. The use of whole blood culture, while not permitting a precise in vitro dissection of the cellular mechanisms governing IL-2 production, may more accurately reflect the mechanisms governing in vivo lymphocyte activation.

Adult↗

Shock-induced modulation of lymphocyte reactivity: suppression, habituation, and recovery.

The present study was designed to evaluate the suppressive effect of different frequencies of signaled-shock presentations on mitogenic reactivity of lymphocytes in Lewis rats, and to assess the recovery of that reactivity at varying times after the shocks. The results showed that the magnitude of decreased reactivity in both the spleen and whole-blood lymphocytes, as determined by mitogenic reactivity to Concanavalin A (Con A), was directly related to the number of shock presentations within a daily session. However, the suppressed reactivity for the spleen cells diminished with repeated sessions of frequent shocks, in contrast to the whole-blood lymphocytes which did not show any habituation. Furthermore, the imposition of different periods of recovery following a single session of frequent shocks showed that the decreased reactivity for the whole-blood lymphocytes extended beyond the immediate period of the shock experience, and took 48 to 96 hours to recover completely. In contrast, the spleen lymphocytes showed complete recovery within 24 hours following the administration of shock. These results establish that the rate of habituation to and recovery from a shock-induced decrease in mitogen reactivity is more rapid for the spleen than whole-blood lymphocytes.

Animals↗

Augmentation of mitogen responsiveness in the aged by a special lipid diet AL 721.

Diminished immune responses in aging may be partially due to alteration of the lipid composition of membrane and a decrease in membrane fluidity. The effect of a daily diet of 10 g active lipid (AL 721) on the mitogen responsiveness of peripheral blood mononuclear cells (PBMC) from aged volunteers was studied. AL 721 is a mixture of lipids from hen egg yolk which was formulated for in vivo rectification of rigidified cell membranes in an attempt to restore proper physiological function. After 3 weeks on the diet, six aged participants displayed a significant increase in lymphocyte responsiveness to mitogens, while in four the responsiveness was unaffected, or increased insignificantly. In all six participants, a decline in lymphocyte responsiveness was observed a week after termination of the diet. Our preliminary results indicate that improvement of immune functions in the aged may be achieved by dietary manipulation of lipids. This innocuous approach seems to be of potential value and merits further studies.

Aged↗

The influence of mouse strain and housing on the immune response.

Five strains of mice housed individually (one per cage) or in a group (five per cage) were immunized with sheep erythrocytes (SRBC) to determine if the major histocompatibility complex (MHC) was associated with altered immune reactivity based on housing. Individually housed mice from two strains which shared neither the H2D and H2K loci, produced more antibody forming spleen lymphocytes to SRBC than group-housed mice. Corticosterone levels were not related to the level of the immune response. Thus, genetic factors related to the MHC do not influence alteration of the immune response which occurs with differential housing conditions.

Animals↗

Effect of in vivo administration of the carcinogen benzo(a)pyrene on interleukin-2 and interleukin-3 production.

B6C3F1 mice were exposed to the environmental carcinogen benzo(a)pyrene, a well known immunosuppressant. The ability of isolated splenocytes to produce and respond to the immunoregulatory molecules interleukin-2 (IL-2) and interleukin-3 (IL-3) was measured. Significant suppression by BaP of IL-2, but not IL-3, production following BaP exposure was observed. Further, exogenous recombinant IL-2 reconstituted the ability of splenocytes from benzo(a)pyrene treated mice to generate IgM antibody producing cells to the T-dependent antigens of sheep red blood cells. These results indicate that one of the cellular target(s) of BaP induced immunosuppression may be the mechanism(s) responsible for lymphokine production and regulation by activated T cells.

Animals↗

Clinical and laboratory evidence of autoimmunity in acute schizophrenia.

A number of assays were performed to assess immunologic function in 28 patients with clinically well-defined schizophrenia. Our data provide laboratory evidence that patients with schizophrenia have characteristics consistent with an autoimmune process, directed to components of the brain, which may participate in either the pathogenesis or etiology of schizophrenia. One-third of our patients had a clinically evident autoimmune syndrome unrelated to their psychiatric illness. Of the nine patients with an autoimmune disease, two had one autoantibody in their serum and five had more than one autoantibodies. Twelve of eighteen patients without clinical evidence of autoimmune disease had no detectable autoantibodies. Mitogenic responses to PHA and PWM were significantly reduced in the patient population when compared to controls. Fifty percent of the patients had an increased percentage (greater than 5%) of blood-borne HLA-DR (+) OKT4 (+) T-helper lymphocytes. Immune reactivity toward brain antigens was sought by measuring lymphocyte transformation to a saline extract of frontal lobe, and by immunoblotting of antigens extracted from frontal lobe, cingulate gyrus, interventricular septum, and hippocampus. Lymphocyte transformation did not reveal differences between patient and control groups. Normal sera were found to contain antibody to some of these brain antigens. However, patients with schizophrenia had antibody to antigens of the hippocampus, septal region and cingulate gyrus which were not encountered during analysis of normal sera.

Acute Disease↗

Inhibited interferon-gamma but normal interleukin-3 production from rats flown on the space shuttle.

Rats were flown on Space Shuttle SL-3 for 1 week. When spleen cells were removed from these rats and challenged with concanavalin-A, interferon-gamma production was severely inhibited, while interleukin-3 production was unaffected compared to ground-based control rats. These data indicate that there is a defect in interferon-gamma production in rats that have been exposed to spaceflight. This defect could contribute to, and be one reason for, immunosuppression observed after spaceflight.

Animals↗