Marijuana and bacterial infections.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
C Newton
Publications and source records attributed to C Newton.
delta-9-Tetrahydrocannabinol (THC) decreases the number of high and intermediate affinity IL-2 receptors of the IL-2 dependent cell line NKB61A2.
Treatment of the cloned NK-cell line (NKB61A2) with the major psychoactive marijuana component, delta-9-tetrahydrocannabinol (THC), for 24 h suppressed IL-2-induced proliferation of these cells in the cytokine concentration range of 0.25-10 pM suggesting that the drug inhibits the functional activity of the high affinity IL-2R. The proliferation inhibitory effect of THC was accompanied by a decrease in the number of high and intermediate affinity IL-2 binding sites as measured by equilibrium binding studies. However, the expression of Tac protein on the surface of these cells was increased as determined by flow cytometry analysis. THC was also shown to decrease proliferation and the number of IL-2 binding sites of cells previously pulsed with IL-2 and then treated with the drug in the absence of IL-2. These results suggest that THC inhibits IL-2-induced proliferation by modulating the expression of high affinity IL-2 receptors (alpha/beta) required for cell activation and also suppresses the ongoing process of functional receptor expression and clonal expansion of cells previously activated by IL-2. Because the number of intermediate binding sites is decreased following drug treatment along with an increase in the expression of Tac protein (alpha chain), the lowering of high affinity sites possibly results from a drug-induced depression of beta chain expression.
Animals↗
Incidence of ocular motility problems following scleral buckling surgery.
The incidence and severity of extraocular muscle imbalance after conventional scleral buckling surgery was determined for 70 eyes of 68 patients with primary rhegmatogenous retinal detachment. Fifty-eight eyes had circumferential silicone explants, 10 eyes had radial sponges and 2 had both. Sixty-five per cent of eyes showed some restriction of ocular motility and 72% of patients had diplopia within their field of binocular single vision (BSV). The more extraocular muscles the explant was placed under, the more directions of gaze were likely to be restricted (p = 0.032). In 84% of eyes the restrictions could be related to the position of the explant. In 87% of patients their diplopia could also be related to the position of the explant. A second retinal detachment operation is more likely to cause restricted motility and more likely to cause diplopia within the expected field of BSV (p = 0.0297).
Adolescent↗
Legionella pneumophila growth restriction in permissive macrophages cocultured with nonpermissive lipopolysaccharide-activated macrophages.
Macrophages can be activated by lipopolysaccharides (LPS) from gram-negative bacteria to evince a number of biological activities, including increased resistance to intracellular infection by opportunistic bacteria. In the present study, intraperitoneal injection of LPS into A/J mice activated peritoneal macrophages so that they resisted subsequent in vitro infection with Legionella pneumophila. Coculture of these macrophages with those from nontreated A/J mice converted the entire population of cells from permissive to nonpermissive. This effect did not appear to be mediated by soluble factors released from the LPS-treated macrophages, since the levels of interleukins-1 and -6 and tumor necrosis factor alpha produced by the macrophages were not found to be markedly elevated at the time when the macrophages from the LPS-treated mice were most effective in converting normal macrophages to nonpermissiveness. Furthermore, macrophages from mice injected intraperitoneally with either interferon or tumor necrosis factor alpha did not evince nonpermissiveness and also did not have the ability to convert normal spleen cells to nonpermissiveness. Polymyxin B, a known inactivator of LPS activity, did not inhibit the macrophages from the LPS-treated mice from inducing this resistance. It seemed unlikely that free LPS released from the macrophages mediated this effect. The results of this study thus showed that macrophages activated by LPS in vivo can evince nonpermissiveness for Legionella growth in vitro and also can induce macrophages from normal, permissive mice to become nonpermissive for Legionella growth in vitro.
Animals↗
Legionella pneumophila induced tumor necrosis factor production in permissive versus nonpermissive macrophages.
The ability of an opportunistic intracellular bacterial pathogen, Legionella pneumophila, to induce tumor necrosis factor (TNF) in macrophages from susceptible A/J or resistant BDF1 and BALB/c mice was determined. Cultures of peritoneal elicited macrophages from these mouse strains produced TNF in response to the Legionella. The TNF levels produced by the macrophages stimulated with either heat-killed Legionella vaccine or lipopolysaccharide were similar and dose dependent, although the amount of TNF produced by macrophages from permissive A/J mice was 2- to 4-fold higher than that produced by macrophages from the nonpermissive mice. Similar differences in TNF levels occurred when macrophages from either permissive or non-permissive mice were infected with viable Legionella. The TNF levels produced by the A/J mouse macrophages increased as a function of time after infection, with a peak of activity on Day 1 or 2, depending upon the initial concentration of the bacteria. Infection of the A/J mouse macrophages with avirulent Legionella resulted in induced levels comparable to those induced by a virulent strain. Although it is widely believed that TNF production by mouse macrophages is related to resistance to infections, the results of this study did not show a relationship between TNF production by macrophages in vitro and resistance versus susceptibility of the macrophage donor mouse strain to Legionella infection.
Animals↗
Delta 9-tetrahydrocannabinol injection induces cytokine-mediated mortality of mice infected with Legionella pneumophila.
Delta 9-Tetrahydrocannabinol (THC) injection modulates immune cell function, but the significance of this in altering host resistance to infection is not understood. In addition, exposure to THC and other drugs of abuse during infection is associated with an acute mortality syndrome. We examined the effect of THC injection on the survival of mice infected with Legionella pneumophila (Lp). Mice given two injections of THC (8 mg/kg)-one 24 hr before and the second 24 hr after a sublethal Lp infection-experienced acute collapse and death. The drug injection after infection caused death; deaths occurred within 30 min after the injection, and neither one nor two drug injections before infection resulted in death. The THC-induced mortality resembled cytokine-mediated shock in both kinetics and symptoms; therefore, sera from drug-treated animals were measured for the acute-phase cytokines tumor necrosis factor (TNF) and interleukin 6 (IL6). The level of each cytokine was significantly elevated by THC treatment, suggesting a role in the observed mortality. To directly test this role, mice were administered a single injection of either anti-TNF alpha, anti-IL6, or a mixture of anti-IL1 alpha and -IL1 beta antibodies 1 hr before the second THC injection. Results showed that each antibody treatment protected the mice, with anti-IL6 being the most effective. Fluctuations in blood granulocytes levels also supported a role of acute-phase cytokines in THC-induced mortality. These results show that THC injection increases the blood levels of acute-phase cytokines in infected animal and that these elevated levels, at least in part, account for the mortality induced by THC injection.
Acute-Phase Proteins↗
Differing macrophage and lymphocyte roles in resistance to Legionella pneumophila infection.
Similar to guinea pig macrophages and human monocytes, macrophages from the peritoneal cavity of thioglycolate pretreated A/J mice are permissive for growth of Legionella pneumophila. In contrast, macrophages from BDF1 mice are not permissive for L. pneumophila. Lymphocytes from A/J and BDF1 mice proliferated in response to Legionella Ag but guinea pig lymphocytes did not. Also, splenocyte cultures from A/J mice treated with either Con A or Legionella vaccine produced supernatants which induced A/J macrophages to restrict Legionella growth, but guinea pig splenocyte culture supernatants obtained after stimulation with L. pneumophila vaccine did not induce Legionella growth restriction activity by guinea pig macrophages. Murine rIFN-gamma but not rIFN-alpha markedly inhibited growth of Legionella in A/J mouse macrophages and monoclonal anti-IFN-gamma antibody neutralized the anti-Legionella activity of culture supernatants from A/J mouse splenocytes responding to Legionella Ag. From these data, IFN-gamma appears to be an important factor in anti-Legionella activity of Ag-activated mouse splenocyte culture supernatants. Cyclosporin A, when given to either A/J or BDF1 mice, reduced the proliferation responses of splenocytes to T cell mitogens and also decreased the IFN production of A/J spleen cells to Legionella Ag. In addition, drug treatment decreased the resistance of A/J mice to Legionella infection as shown by an increase in the number of viable bacteria in the liver. However, injection of drug treated mice with lymphokine-rich splenocyte culture supernatant reconstituted the resistance of these animals. These results suggest an important role for lymphocyte activation and lymphokine production in the resistance of A/J mice to Legionella infection. The greater resistance of BDF1 mice, however, may result from nonpermissive macrophages and responsive lymphocytes. In the case of guinea pigs, susceptibility to Legionella infections may result from both the permissive nature of the macrophages and the relatively unresponsive nature of the lymphocytes in these animals.
Animals↗
Legionella pneumophila infection and cytokine production.
Explore the source record for details and available documents.
Animals↗
Splenocyte blastogenesis suppressed in rats implanted with an osmotic pump.
Rats implanted subcutaneously with an empty osmotic pump connected by a polyethylene catheter to a jugular vein for 5 to 10 days evinced a decreased splenocyte responsiveness to blastogenic stimulation in vitro to bacterial lipopolysaccharide, a known B cell stimulator, as well as to the plant mitogens pokeweed mitogen (PWM), a known stimulator of T and B cells, and Concanavilan A, a known T cell stimulator. The surface of the implanted pumps became infiltrated with lymphoid cells, especially macrophages. Suppression of blastogenic responsiveness after implantation for 10 days with an empty pump or even a pump dispensing pyrogen free saline only in a continuous manner was nearly as marked as that which occurred at 2-5 days after continuous infusion with endotoxin. These depressed blastogenic responses, although less, were also evident when rats were implanted with a catheter into a jugular vein connected by means of a swivel to either an empty pump or one dispensing pyrogen free saline. Suppression of blastogenic responsiveness was not related to alteration in serum complement or corticosteroid levels. Since administration of immunomodulatory substances systemically to individuals often involves implantation of an osmotic pump, investigation into the mechanisms of lymphoid cell suppression associated with an implanted pump itself has potential significance.
Animals↗
Continuous infusion of endotoxin depresses splenic blastogenesis.
Continuous infusion of a sublethal dose of bacterial endotoxin into rats via an implanted osmotic pump markedly affected the blastogenic responsiveness of spleen cells to specific endotoxin as well as to the nonspecific mitogens Con A, PHA or PWM. There was also a marked alteration in lymphoid cell type and number in the spleen of the rats after continuous infusion of endotoxin, with a marked increase in plasma cell infiltration and germinal center formation. There was no significant alteration in glucocorticoid steroid levels. Control rats given saline only for a period of seven days via an implanted pump showed no or minimal effect for the first 5 days and then a delayed depression of blastogenic responses to LPS and to Con A, but this time lag contrasted markedly to the much earlier unresponsiveness of splenocytes from rats infused with endotoxin. Only a slight to moderate cellular infiltration occurred in the spleen of control rats implanted with a pump infusing saline only or an empty pump. Thus endotoxin infusion in a continuous manner via an implanted pump accounted for the early and marked suppression of responsiveness, as well as alteration in spleen size and cellularity.
Animals↗
Enhanced growth of Legionella pneumophila in tetrahydrocannabinol-treated macrophages.
Legionella pneumophila is an opportunistic intracellular pathogen that infects macrophages, both in vivo and in vitro. Tetrahydrocannabinol is a major psychoactive component of marijuana and can affect the functional activity of macrophages. In the present study, it was found that the treatment of macrophage cultures from permissive A/J mice with THC enhanced the growth of Legionella in these cells. Legionella grew much better in macrophages treated with low doses of THC, which caused no alteration in the number or viability of macrophages, as compared with growth in untreated cells. Furthermore, lipopolysaccharide-treated A/J mouse macrophages restricted the growth of Legionella, but this growth restriction was overcome by the addition of THC to LPS-treated macrophage cultures after infection. Thus, it is apparent that THC has the ability to enhance the growth of the intracellular opportunistic pathogen Legionella that grows in A/J mouse macrophages.
Animals↗
Continuous endotoxin infusion suppresses rat spleen cell production of cytokines.
Endotoxin, i.e., lipopolysaccharides, was continuously infused into rats at a nonlethal dose by means of an implanted osmotic pump for up to 2 weeks. The pump was connected to the jugular vein by a polyethylene catheter. Administration of endotoxin via the pump compromised the ability of spleen cells to produce the lymphokines interleukin 1 and tumor necrosis factor after stimulation in vitro with endotoxin. In addition, the ability of the spleen cells to produce alpha/beta-interferon in response to endotoxin in vitro was also examined, as was the capability of the spleen cells to produce gamma-interferon following stimulation with concanavalin A. Suppression of the expected interleukin 1 and tumor necrosis factor production by spleen cells from rats continuously infused with endotoxin was observed. There was also a moderate effect on interferon production, but this was much less. These results provide further findings indicating the unresponsiveness of spleen cells to lipopolysaccharides, as well as to a nonspecific plant mitogen, following continuous infusion of endotoxin into rats via an implanted osmotic pump. Additional studies are needed to determine the mechanisms involved in such suppression.
Animals↗
Suppressive effect of tetrahydrocannabinol on specific T cell subpopulations in the thymus.
The effects of THC (delta-9-tetrahydrocannabinol) on thymocytes from adult BALB/c mice were investigated following in vitro stimulation with the T cell mitogen Concanavalin A (Con A). Con A treatment resulted in a decrease in the relative percent of L3T4+/Ly2+ cells (double positive; immature) with a concomitant increase in the percent of Ly2 cells (suppressor/cytotoxic). No change in the percent of L3T4 cells (helper) occurred. In addition, Con A stimulation resulted in an increase in the absolute number of Ly2 cells, with no change in number of L3T4 cells. Stimulation with the mitogen led to an increase in fluorescence intensity (indicative of relative number of markers) of Ly2 markers on Ly2 single positive cells as well as on L3T4+/Ly2+ cells. There was a moderate mitogen induced increase of L3T4 markers, but only on L3T4 single positive cells. Exposure to THC resulted in a definitive suppressive effect on Con A induced thymus cell proliferation. The suppression was primarily evidenced in the single positive Ly2 subpopulations. Since the thymus is the source of immunocompetent lymphocytes to the secondary lymphoid organs, it seems plausible that marijuana negatively affects maturation of these cells in the developing individual.
Animals↗
Experimental comparison of laser and cryosurgical cilia destruction.
We compared cryosurgery with the argon and carbon dioxide lasers in a rabbit model to evaluate the permanence of eyelash destruction as well as the gross and histologic effects on the eyelid. Each modality was equally effective in preventing eyelash regrowth. Cryosurgery and the carbon dioxide laser produced the greatest acute soft tissue swelling; the carbon dioxide laser produced the most pronounced gross eyelid alterations. The argon laser produced minimal eyelid tissue change. Long-term histologic tissue alterations were not striking and were confined to eyelids treated with cryosurgery and the carbon dioxide laser. We conclude that, of the two lasers, the argon is the best suited to the clinical treatment of trichiasis: it is widely available, more precise in limiting contiguous tissue destruction when delivered through a slit lamp, and is safer for use near the eye.
Animals↗
Pyrrolidino-4-iodotamoxifen and 4-iodotamoxifen, new analogues of the antiestrogen tamoxifen for the treatment of breast cancer.
New tamoxifen analogues were tested for their antiproliferative activity both in vitro and in vivo. Binding studies showed that both 4-iodotamoxifen and pyrrolidino-4-iodotamoxifen and 2.5-fold higher affinities for the estrogen receptor compared with tamoxifen. Pyrrolidino-4-iodotamoxifen was also 1.5-fold more effective in causing inhibition of estrogen-induced growth of MCF-7 cells compared with tamoxifen at 10(-6) M. The 4-iodotamoxifen analogue was similar to tamoxifen in its inhibitory action at 10(-6) M. Antiproliferative activities of these drugs were tested using the nitrosomethylurea-induced rat mammary tumor model. Pyrrolidino-4-iodotamoxifen caused regression in 92% of rats, whereas tamoxifen caused regression in 75% of rats. The agonist activity of the analogues was determined using the immature rat and mouse uterotrophic assays. Both tamoxifen and 4-iodotamoxifen had similar partial agonist activity, and this was greater than that seen with pyrrolidino-4-iodotamoxifen. Furthermore, pyrrolidino-4-iodotamoxifen caused a dose-dependent inhibition of estrogen-induced vaginal cornification, whereas tamoxifen and 4-iodotamoxifen did not. These studies demonstrate that pyrrolidino-4-iodotamoxifen is more effective than tamoxifen in inhibiting tumor regression and that its reduced uterotrophic activity and increased estrogen receptor binding may give it significant clinical advantages over the parent compound.
Animals↗
Multiple binding sites for myogenic regulatory factors are required for expression of the acetylcholine receptor gamma-subunit gene.
The nicotinic acetylcholine receptor (AChR) is a critical component of the mechanism responsible for signal transduction between nerve and muscle. Induction of AChR gene expression occurs during myogenesis when myoblasts exit the cell cycle and fuse to form myotubes. Induction of muscle-specific genes during differentiation is believed to be mediated through the activities of members of the MyoD family of myogenic regulatory factors. At least two of the factors, MyoD and myogenin, function as transcriptional activators. Here we present evidence that MyoD is capable of activating transcription of the mouse AChR gamma subunit gene. We have identified seven potential MyoD-binding sites (E-boxes) within the 5'-flanking DNA of the gamma subunit gene. We demonstrate that two small regions of the 5'-flanking DNA, one containing a pair of E-boxes and the other containing a single E-box, are required for gamma subunit expression in mouse muscle cells. DNase I footprinting indicates that the E-box proximal to the transcriptional initiation site is capable of interacting directly with MyoD. Furthermore, site-directed mutational analysis indicates that the single E-box is necessary for transactivation by MyoD and expression of the gamma subunit promoter region in muscle cells.
Animals↗
Bilateral herpes simplex keratitis in a patient with graft-vs-host disease.
Explore the source record for details and available documents.
Adult↗
Suppression of T lymphocyte subpopulations by THC.
Explore the source record for details and available documents.
Animals↗