Ethanol affects macrophage production of IL-6 and susceptibility to infection by Legionella pneumophila.
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Animals↗
Biomedical subjects
H Friedman
Publications and source records attributed to H Friedman.
Contrasting effect of delta-9-tetrahydrocannabinol on IL-2 activity in spleen and lymph node cells of mice of different ages.
The purpose of this study was to investigate the immunomodulatory effect of delta-9-tetrahydrocannabinol (THC) on spleen and lymph node cells of adult and young mice. When plant mitogen (Con A or PHA) stimulated cells were treated with varying doses of THC, the proliferation of spleen and lymph node cells of adult and young mice was suppressed. This suppression was found to be compatible with a decrease in number of Tac positive cells as well as a down-regulation of IL-2 activity. In contrast, when these cells were stimulated with anti-CD3 antibody in combination with THC, the pattern of the immunomodulation as well as the absolute effects of the drug differed with the age of the mice as well as the organ of origin of the cells. In this regard, anti-CD3 antibody stimulation in combination with low doses of THC stimulated proliferation of splenocytes obtained from adult mice. The stimulation was found to reflect an increase in the number of both suppressor/cytotoxic T cells (Ly2 cells) as well as Tac positive cells. IL-2 activity was found to be enhanced under these conditions. This up-regulation of responsiveness was not seen in either lymph node cells of adult or young mice or in spleen cells of young mice. The THC modulating activity is directly related to its effect on both IL-2 activity and generation of Tac positive cells in spleen and lymph node cells of both adult and young mice. It appears, therefore, that not only age, but also lymphoid organ system differences are important factors in terms of considering the effects of drugs of abuse.
Aging↗
Age related immunomodulation in murine splenocytes induced by delta-9-tetrahydrocannabinol (THC).
The purpose of this study was to investigate the immunomodulatory effects of THC (delta-9-tetrahydrocannabinol) on spleen cells of young (2 week), adult (2 month) and old (15 and 24 month) mice. THC has been shown by many investigators to suppress various immune parameters in adults. Since immune capabilities are already diminished at either age extreme, it seemed relevant to investigate the effect of this drug with aging. It was found that when spleen cells were stimulated with concanavalin A (Con A), phytohemagglutinin (PHA) or anti-CD3 antibody, the magnitude of the proliferation was greatest in the adult and less at either age extreme. When Con A or PHA stimulated cells were treated with varying doses of THC, the proliferation of cells was suppressed with the general pattern of suppression similar at all ages. However, the absolute magnitude of the resultant suppression was greater in young and old mice. In contrast, when the cells were stimulated with anti-CD3 antibody and THC, both the pattern of the immunomodulation as well as the absolute effects differed with age of the mice. In this regard, anti-CD3 stimulation and low doses of THC stimulated lymphocyte proliferation in the adult mice. This combination was found to increase CD3 positive cells of the Ly2 subclass (effector/suppressor) in the adult. At either age extreme, the THC induced enhancement of proliferation was not as apparent. In addition, the cells from mice at either age extreme were more readily suppressed at 7 micrograms THC than were adult cells. It appears, therefore, that age is an important variable in terms of considering the effects of drugs of abuse.
Adjuvants, Immunologic↗
Cocaine suppresses proliferation of phytohemagglutinin-activated human peripheral blood T-cells.
Cocaine has been reported to modulate the immune system of experimental animals. Also, we observed that the drug suppresses the phytohemagglutinin (PHA)-induced proliferation of human peripheral blood mononuclear cells (PBMCs) but at concentrations extremely high relative to those seen in the blood of drug abusers. This suggested that cocaine had a relatively weak effect when tested under conditions of optimum proliferation. We, therefore, decided to examine the effect of lower concentrations of cocaine on suboptimum PHA-induced proliferation. At 0.09-12 microM, cocaine had no effect on the proliferation of PBMC in response to 0.2 micrograms/ml PHA. However, depleting the population of B-cells and monocytes resulted in a drug-induced suppression of the residual T-cells. Maximum suppression by cocaine was observed at 3 microM with both higher and lower concentrations of the drug causing less suppression. Suppression of proliferation was not influenced by either the age or sex of the peripheral blood lymphocytes (PBL) donors. The suppression of T-cell-enriched PBLs induced by cocaine could be eliminated by increasing the dose of the mitogen but was enhanced by preincubating the cells with the drug for 24 h. Also, the drug suppressed cytosolic free calcium mobilization in Fura 2/AM loaded enriched T-cell populations. These results show that cocaine moderately but consistently suppresses PHA-induced proliferation of T-cells from random blood donors at drug concentrations observed in drug abusers. The suppression is only evident under conditions of suboptimum proliferation and is accompanied by a corresponding decrease in the mobilization of cytosolic free calcium. It is suggested that the weak suppressive effect of cocaine is reversed by either helper factors produced by accessory cells or increasing concentrations of mitogen. These factors when present possibly overcome a drug-induced reduction in calcium mobilization and lymphocyte activation.
Adult↗
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↗
Increase in cytoplasmic free calcium in murine splenocytes following stimulation with anti-CD3 antibody in the presence of delta-9-tetrahydrocannabinol.
It has been previously shown that when mitogens such as concanavalin A (Con A) or phytohemagglutinin (PHA), are used to stimulate lymphoid cells which are treated with varying doses of delta-9-tetrahydrocannabinol (THC), the proliferation of splenocytes from mice of different ages is suppressed. In contrast, when these cells were stimulated with anti-CD3 antibody in combination with THC, lower doses of THC stimulated proliferation of the splenocytes. This stimulation occurred only if the spleens were obtained from adult (2 month) mice as opposed to cells from young (2 week) or aged (24 month) mice. In order to more completely understand this age related differential effect, mobilization of cytosolic free Ca2+ was studied in this system, using fluorescent Ca2+ probes and spectrofluorometry. It was found that adult splenocytes pretreated with anti-CD3 antibody responded to cross-linking by anti-IgG antibody with a further rise in intracellular free Ca2+. Such an increase in Ca2+ was not seen with cells derived from either young or old mice. A similar phenomenon occurred when 5 micrograms/ml THC was used in place of the anti-IgG antibody. Thus, adult spleen cells exposed to both delta-9-THC and anti-CD3 antibody displayed an increase in intracellular free calcium whereas spleen cells from very young mice failed to respond in this manner. Interestingly, when 11-hydroxy-THC, another metabolite of marijuana, was used instead of the delta-9-THC, no rise in intracellular Ca2+ influx was seen in any age group of mice tested. These results emphasize the differential effect of THC on splenocytes from individuals of different ages.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Differences in HLA class II alleles of isolated South American Indian populations from Brazil and Argentina.
We have studied the HLA class II alleles in 277 South American Indians, which included Argentinian tribes from the Gran Chaco: Toba (n = 135), Toba-Pilaga (n = 19), Mataco-Wichi (n = 49), and Xavantes, a tribe from Central Brazil (n = 74). In the Brazilian tribe, only four DR groups were found: DRB1*1602 (gf = 0.303), DRB1*04 including DRB1*0404 (gf = 0.070) and DRB1*0407 (gf = 0.077), DRB1*0802 (gf = 0.265), and DRB1*1402 (gf = 0.303). The HLA class II allele frequencies were similar among the different Argentinian tribes, and 90% of DRB1 alleles belonged to three families: DRB1*04 (including DRB1*0403, DRB1*0404, DRB1*0407, DRB1*0411, and DRB1*0417), DRB1*0802, and DRB1*14 (including DRB1*1402 and DRB1*1406). At the DPB1 locus, we found only seven alleles, the most frequent being DPB1*0402. Comparison of HLA class II alleles with those of North American Indians that we have previously studied shows that the frequency of some HLA class II alleles in Brazilian Xavantes resembles that of North American Indians more than that of the Argentinian Indian tribes. The allele DRB1*0417 was found exclusively in this population.
Adult↗
Human submandibular saliva aggregates HIV.
Incubation of HIV with human whole, parotid, or submandibular saliva leads to a decrease in viral infectivity in Sup-T1 cells. The effect is most pronounced with submandibular saliva. Inhibition is seen within 2 min, and increases with time. There is little inhibition seen after incubation of saliva with HSV, and no effect with adenovirus, suggested that there is some viral specificity. Electron microscopic studies revealed that HIV-saliva aggregates are trapped in 0.45-microns pore size nitrocellulose filters. If these inhibitory effects are manifest in vivo, this could account for the low level of virus detected in oral secretions.
Adenoviridae↗
Case report: spinal cord compression due to metastatic hepatocellular carcinoma.
Hepatocellular carcinoma is an uncommon cancer in the United States. Its initial presentation as spinal cord compression due to vertebral metastasis is rare. This article reports a case of radiculopathy and rapidly developing spinal cord compression because of bony metastasis from this form of liver cancer. This article also reviews pertinent literature and discusses the diagnostic modalities for early detection.
Carcinoma, Hepatocellular↗
Genetic markers for susceptibility to endemic Brazilian pemphigus foliaceus (Fogo Selvagem) in Xavante Indians.
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Alleles↗
Granulocyte colony-stimulating factor potentiates anti-Candida albicans growth inhibitory activity of polymorphonuclear cells.
Granulocyte colony-stimulating factor (G-CSF) stimulates a subset of granulocyte colony forming cells and when administered to neutropenic individuals results in recovery of blood neutrophil numbers to normal levels. Therefore, G-CSF may be a useful therapeutic agent for infections in immunocompromised hosts. However, to date there has been only limited information that G-CSF activates the antimicrobial activity of neutrophils. In the present study, we found that recombinant G-CSF promotes the anti-Candida albicans activity of normal human blood polymorphonuclear (PMN) cells in vitro using both a 3H-glucose uptake procedure and a Candida colony counting assay. As little as 0.1 ng/ml G-CSF induced significant anti-Candida activity in the PMN cultures. G-CSF treatment also enhanced superoxide anion production by the PMNs in response to f-MLP as determined by the superoxide dismutase inhibitable cytochrome C reduction method. Such results show that G-CSF can promote the antimicrobial activity of peripheral blood PMNs against C. albicans.
Candida albicans↗
Anticipation of handling the dead: effects of gender and experience.
In addition to the direct psychological effects of disaster stressors, anticipation of stress can itself be debilitating. We examined the relationship between the anticipated stress of handling the dead and gender and experience. Experienced persons had lower anticipated stress than inexperienced persons. Inexperienced, females had higher anticipated stress than inexperienced males; experienced males and females did not differ. Results provide support for an 'inoculation' theory of stress buffering in disaster workers.
Adaptation, Psychological↗
Antibody-mediated enhancement of Legionella pneumophila-induced interleukin 1 activity.
The ability of antibody specific for Legionella pneumophila to enhance the induction of interleukin 1 (IL-1) production by murine peritoneal, splenic, and pulmonary macrophages in response to the bacterium was examined. Two preparations of L. pneumophila were utilized, a formalin-killed whole-cell preparation and viable bacteria. We measured both secreted (sIL-1) and cell membrane-associated (mIL-1) activities after incubation of the macrophages with the bacterial preparations in the presence or absence of the antibody. Both bacterial preparations induced sIL-1 and mIL-1 activities in each of the macrophage populations tested. These activities were generally enhanced by pretreating the bacteria with antibody, with the greatest enhancing activity observed for the formalin-killed preparations at lower doses of bacteria.
Animals↗
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↗
Lipopolysaccharide restores anti-Candida albicans growth inhibition activity of polymorphonuclear neutrophils from retrovirus-immunosuppressed mice.
It has been documented that the immune function of leukocytes may be markedly suppressed after infection of mice with the murine retrovirus Friend leukemia virus (FLV). Antimicrobial activity of polymorphonuclear neutrophils (PMNs) against Candida albicans is impaired after retrovirus infection of mice, and this occurs as early as 3 days after infection of genetically susceptible BALB/c mice. By 2 weeks after infection, there was essentially very little growth inhibition of C. albicans by PMNs from the FLV-infected mice. However, when bacterial lipopolysaccharide (LPS), a known activator of macrophages and PMNs, was added to PMNs from the FLV-infected mice, anti-C. albicans activity was restored to normal levels. This restoration of anti-C. albicans activity of FLV-infected mouse PMNs was observed after stimulation with as little as 0.01 micrograms of LPS per ml. The data obtained show that the impaired antimicrobial function of PMNs from retrovirus-infected mice can be readily restored by a biological response modifier such as bacterial LPS.
Animals↗
Fatigue in Parkinson's disease.
Fatigue is a common but poorly understood symptom in Parkinson's disease (PD). Using previously validated scales, we asked 58 nondemented PD patients and 58 controls to fill out questionnaires assessing fatigue and depression and found that PD patients were more depressed and more fatigued than age-matched controls. Although fatigue correlated with depression but not with disease severity, many nondepressed patients had significant complaints of fatigue.
Aged↗
Mesenrhombencephalitis: MR findings in nine patients.
OBJECTIVE: Mesenrhombencephalitis is a serious form of brainstem inflammation predominantly involving the deep and vital portions of the brain, that is, the mesencephalon (midbrain) and rhombencephalon (pons, medulla). Mesenrhombencephalitis is difficult to diagnose on the basis of clinical and laboratory findings alone, and access to this portion of the brain for surgical biopsy carries high morbidity. We describe the MR appearance of mesenrhombencephalitis and correlate the imaging findings with clinical information. MATERIALS AND METHODS: Unenhanced and contrast-enhanced MR images of nine patients with mesenrhombencephalitis were reviewed retrospectively and correlated with clinical, laboratory, and pathologic data. The patients were categorized according to the cause of the disease: three had herpes simplex, one had Listeria monocytogenes, and five had mesenrhombencephalitis of undetermined cause. The three patients with clinical and MR evidence of herpes simplex mesenrhombencephalitis (one confirmed by brain biopsy) were comatose at presentation, with cranial nerve abnormalities in two and seizures in one. One patient with L. monocytogenes (established by blood culture) had cranial nerve palsies, fever, and pain in the ear. Five additional patients had headache (three), fever (three), nausea and vomiting (four), cranial nerve palsies (three), coma (two), and hyporeflexia (one) or hyperreflexia (four). Brain biopsy performed in two patients revealed chronic inflammation of unspecified cause; in one, it was compatible with viral encephalitis. RESULTS: MR images in three patients with herpes simplex mesenrhombencephalitis showed T2 signal hyperintensity in the midbrain (two), pons (one), medulla (one), and temporal lobes (three). Parenchymal foci of hemorrhage (methemoglobin, one patient) and leptomeningeal enhancement (one patient) were identified in the temporal lobes. T2-weighted MR images in one patient with L. monocytogenes showed signal hyperintensity in the brainstem, vermis, midbrain, and internal capsules. On T1-weighted images, low signal was present in these areas, which enhanced with paramagnetic contrast agents. In the remaining five patients, T2-weighted MR images showed patchy signal hyperintensity in the pons, medulla, and thalamus in three each and in the midbrain and temporal lobes in one each. T1-weighted MR images showed normal findings (two) or signal hypointensity in the thalamus and pons in one patient each. Areas of leptomeningeal and parenchymal enhancement were identified in one patient each. Brainstem swelling was seen in three patients, one of whom had petechial hemorrhage in the pons and hydrocephalus. CONCLUSION: Mesenrhombencephalitis is a serious illness that is diagnosed by a combination of imaging, clinical, laboratory, and pathologic studies. MR imaging may be crucial to the early diagnosis of this illness, and radiologists must be familiar with this uncommon entity and its MR findings in order to make timely diagnoses and facilitate treatment.
Adult↗
MR evaluation of the anterior cruciate ligament: value of supplementing sagittal images with coronal and axial images.
OBJECTIVE: Most studies evaluating the anterior cruciate ligament have focused on sagittal MR images for the diagnosis of injury. Limitations of sagittal images have been reported, however, including nonvisualization and incomplete visualization of the ligament. This study was undertaken to assess the value of adding coronal and axial MR images to sagittal images in the evaluation of the anterior cruciate ligament. MATERIALS AND METHODS: We reviewed oblique sagittal T1-weighted, coronal T2-weighted, and axial T2-weighted images to determine the status of the anterior cruciate ligament in 325 patients. All patients had arthroscopy. Sagittal images were initially interpreted alone and then in combination with coronal and axial images. RESULTS: Sagittal T1-weighted images alone had a 94% sensitivity and an 84% specificity for determining the status of the anterior cruciate ligament. A multiplanar evaluation of the anterior cruciate ligament resulted in a change in MR interpretation in 21 patients (6%), which led to an improved sensitivity of 98% and a specificity of 93%. Diagnostic confidence was improved in an additional 14 patients (4%). CONCLUSION: Our results show that the efficacy of MR imaging for the detection of anterior cruciate ligament tears is greater when axial and coronal images are used in combination with sagittal images than when sagittal images are used alone.
Adult↗