Biomedical subjects

Walter Royal

Publications and source records attributed to Walter Royal.

7 recordsLinked to original sources

PubMed2006

CCL5 modulates pneumococcal immunity and carriage.

Understanding the requirements for protection against pneumococcal carriage and pneumonia will greatly benefit efforts in controlling these diseases. Recently, it has been shown that genetic polymorphisms can result in diminished expression of CCL5, which results in increased susceptibility to and progression of infectious diseases. We show that CCL5, together with Th cytokine mRNA expression, is temporally up-regulated during pneumococcal carriage. To determine the contribution of CCL5 to pneumococcal surface antigen A-specific humoral and cellular pneumococcal immunity, mice were treated with anti-CCL5 or control Abs before and during Streptococcus pneumoniae strain EF3030-challenge for the initiation of carriage. CCL5 blockade resulted in a decrease of CD4(+) and CD8(+) T cells as well as CD11b(+) cells in the spleen, cervical lymph node, lung, and nasopharyngeal associated lymphoid tissue during the recognition phase of the pneumococcal adaptive immune response. CCL5 blockade significantly reduced the Ag-specific IgG2a and IgG1 Abs in serum and IgA Ab levels in nasal washes. These decreases also corresponded to reductions in Ag-specific T cell (mucosal and systemic) responses. CCL5 inhibition resulted in decreasing the quantity of IL-4- and IFN-gamma-secreting CD4(+) T cells and increasing the number of Ag-specific IL-10-producing CD4(+) T cells; these changes combined also corresponded with the transition from pneumococcal carriage to lethal pneumonia. These data suggest that CCL5 is an essential factor for the induction and maintenance of protective pneumococcal immunity.

Animals↗

PubMed2006

Amebic meningoencephalitis.

Amebic meningoencephalitis is an uncommon infection of the central nervous system (CNS), the consequences of which are devastating in the vast majority of patients. Although it is fortunate that few individuals are affected by the infection, with such a low incidence of the disease it has been difficult to develop and test treatment approaches that, with the appropriate implementation, could be broadly effective. As might be expected, the currently available information suggests the possibility that early diagnosis and treatment can result in improved survival and possible recovery. It is also possible that some ameba families and strains may be less pathogenic than others. In order to initiate potentially effective interventions during the early stages, it is necessary to be aware of the clinical and epidemiologic features that distinguish primary from secondary CNS amebic infection and of the various organisms that are associated with these forms of disease. This is not only true for patients with the more classical presentations of these infectious syndromes but also for those who are "culture negative" for common human CNS pathogens. Such information would assist greatly in further delineating the etiopathogenesis and spectrum of disease that is associated with amebic infection of the CNS, as well as potentially effective therapies.

Journal Article↗

PubMed2005

Retinoid-induced mu opioid receptor expression by phytohemagglutinin-stimulated U937 cells.

Opioid use may be associated with an increased risk of neurological disease in human immunodeficiency virus (HIV) infection through effects on immune cell function. Studies were performed to examine the effects of specific retinoid receptor activation on mu opioid receptor (MOR) production by phytohemagglutinin (PHA)-stimulated U937 cells, a mononuclear cell line. PHA stimulation increased activation of the MOR promoter as well as levels of MOR mRNA, total receptor protein in cell lysates, and surface and cytoplasmic receptor expression. Retinoid X receptor (RXR) agonist and retinoic acid receptor (RAR) antagonist further increased MOR expression by the PHA-stimulated cells. In contrast, MOR expression was suppressed by RAR agonist and by RXR antagonist. Finally, opioid receptor binding was also increased by RXR agonist and RXR antagonist; no increase in binding occurred in the presence of RAR agonists and RXR antagonist. All together, these studies suggest that MOR expression in U937 cells can be differentially regulated by specific retinoid receptor activation. Such effects may have important clinical relevance for opioid users with HIV infection, including individuals with neurological disease.

Cell Differentiation↗

PubMed2004

Do drugs of abuse impact on HIV disease?

Drug abuse, certain lifestyles, access and adherence to drug abuse treatment, and medical consequences of drug abuse remain as important factors that impact on HIV disease among AIDS patients worldwide. Most in vitro and in vivo studies show a significant impact on HIV disease. Epidemiological studies in the past have failed to support these observations. However, new and limited evidence shows that drug abuse may accelerate HIV disease in humans. Research is needed to design new or refine known techniques that more closely mimic natural conditions of HIV disease, and perform additional assessments of basic laboratory, clinical, and epidemiological data to determine whether drug abuse significantly impacts on HIV disease.

Acquired Immunodeficiency Syndrome↗

PubMed2004

RXR-induced TNF-alpha suppression is reversed by morphine in activated U937 cells.

Deficiency in vitamin A has been associated with adverse clinical outcomes in drug users with HIV-1 infection. Retinoids have been demonstrated to suppress proinflammatory cytokine production by immune cells in vitro. These effects are induced by ligand-mediated activation of the retinoid receptors--retinoic acid receptor (RAR) and retinoid X receptor (RXR). In these studies, the effects of all-trans-retinoid acid (ATRA, a RAR agonist), 9-cis-retinoic acid (9cis RA; RAR and RXR agonist), LG101305 (RXR agonist), LG100815 (RAR antagonist) and LG101208 (RXR antagonist) on TNF-alpha production by phytohemagglutanin-activated U937 cells and the modulation of these effects by morphine were examined. TNF-alpha production was suppressed in all cultures exposed to retinoid agonist and antagonist agents. For cells exposed to RXR agonists or RAR antagonist, incubation with morphine resulted in the reversal of TNF-alpha suppression and this effect was inhibited by naloxone. These data suggest that interactions between RXR and morphine are involved in the immune effects of retinoids on TNF-alpha production by activated U937 cells. Such information may be important for understanding interactions between drugs of abuse and immune function in individuals with chronic proinflammatory states such as HIV-1 infection.

Alitretinoin↗

PubMed2004

Nuclear receptor activation and interaction with morphine.

Nervous system disease in HIV infection is associated with toxic damage induced by effects from proinflammatory responses and oxidative stress, and such effects may be more prominent among opioid abusers. In these studies, the effects of activating retinoid receptor (retinoic acid receptor (RAR) and retinoid X receptor (RXR)) and peroxisome proliferator activated receptor (PPAR) gamma, which belong to the steroid-lipid nuclear receptor family, on tumor necrosis factor (TNF)-alpha production and inducible nitric oxide synthase (iNOS) gene expression by stimulated U937 and SVG cells, respectively, were examined. Also studied were the effects of morphine on these responses. These studies showed that, in stimulated cells, the observed responses were suppressed by activation of the nuclear receptors as compared to non-stimulated control cells. Moreover, in phytohemagglutinin (PHA)-stimulated U937 cells, morphine reversed the TNF-alpha suppression that was induced by LG101305 and ciglitazone. Preliminary data in SVG cells suggest a tendency for morphine to have a similar effect on LG101305-exposed SVG cells stimulated with a combination of lipopolysaccharide (LPS) and interferon-gamma, whereas this effect was not induced when these cells were incubated with ciglitazone. Therefore, specific nuclear receptor activation may be potentially beneficial in the treatment of neurological disease associated with HIV infection and may show specific interactions with opioids. The mechanisms that underlie these effects require further study.

Astrocytes↗

PubMed2002

Pigment epithelium-derived factor is elevated in CSF of patients with amyotrophic lateral sclerosis.

Pigment epithelium-derived factor (PEDF), a recently defined retinal trophic factor and anti-angiogenic factor for the eye, is also present in the CNS and is a motor neuron protectant. We asked whether PEDF levels in CSF are altered in patients with amyotrophic lateral sclerosis (ALS). Pigment epithelium-derived factor protein was detected by quantitative western blot analysis with a PEDF-specific antiserum. Levels of PEDF in CSF, expressed as a ratio to total CSF protein, were significantly elevated 3.4-fold in 15 patients with ALS compared with neurologic disease controls (p < 0.0003). This increase does not seem likely to reflect up-regulation of PEDF synthesis in muscle in response to denervation, as CSF PEDF was not elevated in severe denervating diseases other than ALS. Nor does the increase represent some non-specific release in neurodegeneration, as CSF PEDF was not elevated in other neurodegenerative diseases. While the mechanism of this presumably reactive increase is not known, the distinctive, surprisingly elevated level of PEDF in the CSF may be an autoprotective reaction in ALS.

Adult↗