Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A woman, aged 26 years, who died of progressively worsening demyelinating encephalomyelitis in the course of 4 years is reported. The neuropathological findings included large subcortical softenings in the cerebral hemispheres, tiny perivenous demyelinated foci in their neighborhood and scattered in the white matter. There was an acute vasculitis with fibrinoid exudation in the affected as well as unaffected areas. Focal perivenous mononuclear cell infiltrations are conspicuous in the white matter. The laboratory and postmortem examinations suggested a collagen disease like SLE. The abnormalities included marked increase of serum gamma-globulin, especially of IgG, and elevation of CRP, RA, and ANA titer, moderate thickening of the basement membranes of the renal glomeruli, onion skin-like periarteriolar fibrosis in the spleen, fibrous pericarditis and periadventitial fibrosis of myocardial arteries. Bilateral degeneration of the spinal posterior columns and dorsal roots was also observed. A probable relationship of the modified features in this example of demyelinating encephalomyelitis with abnormal immune mechanisms in the background is discussed.
 ...
PMID:A case of demyelinating encephalomyelitis with some resemblance to collagen disease. 7 51

A comparative study of the correlation between reproduction and the interferon-inducing activity of viruses in chick embryo fibroblast cultures was carried out with members of different groups of togaviruses: alphavirus (Venezuelan equin encephalomyelitis viru, VEE) and flavivirus (Saint Louis encephalitis virus, SLE). The correspondence between cycles of accumulation of intracellular and extracellular viruses and the dynamics of interferon production the synthesis of which began early in the stage of exponential virus growth and correlated with the dynamics of their reproduction, was determined. Reproduction of the viruses was found to be directly dependent upon the multiplicity of infection; optimal infecting doses for the induction of the largest amounts of interferon were established. The calculations of the reproductive activity of VEE and SLE viruses showed their yield per one cell to be approximately 10,000 PFU and 1,000 LD50, respectively. Partial thermal inactivation of the viruses resulted in decreased yields of the infectious virus and interferon production. The regimen of thermal inactivation at which infectivity was lost completely, but the interferon-inducing capacity was retained probably due to residual synthesis of viral RNA was established for VEE virus. From the fact that the pattern of realization of genetic information is similar for both viruses, a similar mechanism of interferon synthesis induction is assumed.
 ...
PMID:[Reproduction and interferogenic activity of togaviruses]. 89 98

We now have substantial evidence demonstrating noradrenergic sympathetic and peptidergic innervation of both primary and secondary lymphoid organs. We have established criteria for norepinephrine, and some of the neuropeptides, as neurotransmitters, and have found changes in immune responsiveness following pharmacological manipulation of noradrenergic sympathetic or peptidergic nerves. Classic receptor binding studies have demonstrated a wide variety of target cells that possess beta-adrenoceptors and receptors for neuropeptides on cells of the immune system, including lymphocyte subsets, macrophages, accessory cells, or stromal elements. In this chapter we describe noradrenergic and peptidergic innervation of primary and secondary lymphoid organs in development, at maturation and during the normal aging process, and discuss possible functional implications of direct neural signals onto cells of the immune system at critical time points in the lifespan of an animal. Further, we examine for involvement of noradrenergic sympathetic and peptidergic innervation in the development and progression of several autoimmune disorders, including adjuvant-induced arthritis, New Zealand mice strains as a model for hemolytic anemia and lupus-like syndrome, and the experimental allergic encephalomyelitis model for multiple sclerosis.
 ...
PMID:Innervation of lymphoid organs and implications in development, aging, and autoimmunity. 131 62

SK&F 105.685 (N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine+ ++ dihydrochloride) is a novel azaspirane with beneficial activity in rat models of adjuvant-induced arthritis and experimental autoimmune encephalomyelitis as well as in the murine lupus model. The mechanism of action in these models appears to be the induction of non-specific suppressor cell activity which is measured by the ability of cells from treated animals to partially inhibit the proliferative response of lymphocytes from control animals to concanavalin A (ConA) in a co-culture assay. In this study we have shown that oral administration of 0.1-3 mg/kg/day of SK&F 105.685 to purebred beagle dogs induced suppressor cell activity in the spleen and bone marrow but not in the peripheral blood. In vitro, SK&F 105.685 partially suppressed the proliferative response of dog splenocytes to the mitogens phytohemagglutinin (PHA), ConA and, to a lesser extent, pokeweed mitogen (PWM). Peripheral blood lymphocytes (PBLs) differed from spleen cells in their susceptibility to suppression by SK&F 105.685. While the PWM and ConA responses of PBLs and spleen cells showed similar levels of inhibition, the PHA response of PBLs, in marked contrast to spleen cells, was resistant to suppression by the compound. Our results show that the immunoregulatory effects of SK&F 105,685 are not limited to rodents and that suppressor cell activity in dogs is induced quickly and by relatively low doses of the compound.
 ...
PMID:Induction of suppressor cell activity in vivo and suppression of lymphoproliferative responses in vitro by SK&F 105.685 in the dog. 153 91

The active vitamin D metabolite 1,25-dihydroxyvitamin D3 [1,25-D3] is thought to promote many of its actions through interaction with a specific intracellular receptor. The discovery of such receptors in monocytes and activated lymphocytes has led investigators to evaluate the role of the hormone on the immune system. The sterol inhibits lymphocyte proliferation and immunoglobulin production in a dose-dependent fashion. At a molecular level, 1,25-D3 inhibits the accumulation of mRNA for IL-2, IFN-gamma, and GM-CSF. At a cellular level, the hormone interferes with T helper cell (Th) function, reducing Th-induction of immunoglobulin production by B cells and inhibiting the passive transfer of cellular immunity by Th-clones in vivo. The sterol promotes suppressor cell activity and inhibits the generation of cytotoxic and NK cells. Class II antigen expression on lymphocytes and monocytes is also affected by the hormone. When given in vivo, 1,25-D3 has been particularly effective in the prevention of autoimmune diseases such as experimental autoimmune encephalomyelitis and murine lupus but its efficacy has been limited by its hypercalcemic effect. Synthetic vitamin D3 analogues showing excellent 1,25-D3-receptor binding but less pronounced hypercalcemic effects in vivo have recently enhanced the immunosuppressive properties of the hormone in autoimmunity and transplantation.
 ...
PMID:Immunomodulatory role of 1,25-dihydroxyvitamin D3. 164 50

SK&F 105685 (N,N-Dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine+ ++ dihydrochloride) is a novel azaspirane with beneficial activity in animal models of autoimmune diseases such as adjuvant-induced arthritis and experimental autoimmune encephalomyelitis in the Lewis rat and lupus-like disease in the MRL mouse. The effect of SK&F 105685 on the proliferation of rat lymphoid cells was examined in vitro. The compound inhibited the proliferative response of spleen, thymus and lymph node cells to the mitogen concanavalin A (Con A) in a dose-dependent manner but had little or no effect on the mitogenic response of peripheral blood lymphocytes. Although less potent than cyclosporin A, SK&F 105685 was able to inhibit the proliferation of spleen cells stimulated with PMA and ionomycin or the mitogens phytohemagglutinin (PHA), Con A and pokeweed mitogen (PWM). Relatively early event(s) in cell proliferation were affected by SK&F 105685 since delaying addition of the drug by 24 to 48 hours after Con A stimulation of rat spleen cells resulted in reduced levels of suppression. The mode of action of SK&F 105685 appeared to differ from that of cyclosporin A or rapamycin. Unlike cyclosporin A, SK&F 105685 did not affect IL-2 production by Con A-stimulated spleen cells or the IL-2-producing Jurkat cell line, but, like rapamycin, the compound significantly reduced the IL-2-induced proliferation of rat ConA blasts. These results suggest that inhibition of lymphocyte proliferation by SK&F 105685 may require the activity of an intermediate effector cell(s) present in susceptible populations such as cells from the spleen, thymus, lymph nodes and Con A blast preparations but absent or present in low numbers in resistant populations such as peripheral blood cells. Indomethacin and NG-monomethyl-L-arginine (NGMMA), a competitive inhibitor of nitric oxide synthase, were both unable to relieve SK&F 105685-induced suppression of splenic Con A responses thereby ruling out a role for the production of prostaglandins or nitric oxide by macrophages as an intermediate in drug-mediated suppression. In summary, SK&F 105685 was unable to inhibit lymphoproliferative responses by a mechanism distinct from that of cyclosporin A or rapamycin and which appears to involve regulation of cellular interactions rather than a direct effect on responding lymphocytes.
 ...
PMID:Inhibition of lymphoproliferative responses by SK&F 105685, a novel anti-arthritic agent. 166 43

Using the patch-clamp technique in combination with fluorescence microscopy we have found an abnormality in voltage-gated K+ channel expression in T cells that represents the first molecular marker linking three disparate autoimmune diseases in mice. CD4-CD8-Thy-1.2+ (double-negative or DN) lymphocytes from every known murine model for systemic lupus erythematosus, type-1 diabetes mellitus and experimental allergic encephalomyelitis exhibit abnormally high numbers of an unusual K+ channel, termed type l compared to their phenotypic counterparts in normal mice. Other T cell subsets from these diseased mice retain their normal pattern of K+ channel expression. The unique K+ channel phenotype of DN T cells arises in parallel with the onset of autoimmunity. Although mitogen-activated T cells and rapidly proliferating thymocytes exhibit large numbers of K+ channels, these channels are of an electrophysiologically distinct type called n. Thus, abundant expression of type l K+ channels appears to be a useful marker for DN T cells associated with autoimmunity and may provide a valuable tool for delineating the role of DN T cells in the pathogenesis of autoimmune diseases.
 ...
PMID:Autoimmune diseases linked to abnormal K+ channel expression in double-negative CD4-CD8- T cells. 197 90

Expression of voltage-gated K+ channels in mAb-defined T cell subsets from normal mice and mice with experimental autoimmune arthritis was studied with the patch-clamp whole-cell recording technique in combination with fluorescence microscopy. CD4+CD8- Th cells from DBA/1 LacJ mice with type II collagen arthritis expressed low levels of type n K+ channels, and CD4-CD8+ T cells (cytotoxic) showed small numbers of type l or n' K+ channels, like their phenotypic counterparts in normal mice. CD4-CD8-Thy-1.2+ (double negative or DN) T cells from the diseased mice, however, displayed an abundance of type l K+ channels compared to DN T cells in normal mice, or mice immunized with CFA. Furthermore, the aberrant expression of type l K+ channels correlated with the presence of active disease. DN T cells from mice with SLE, type-1 diabetes mellitus, and experimental allergic encephalomyelitis, also exhibited a high number of type l K+ channels. These results suggest that expression of numerous type l K+ channels may be a useful marker for DN T cells associated with these autoimmune disorders.
 ...
PMID:CD4-CD8- T cells from mice with collagen arthritis display aberrant expression of type l K+ channels. 197 26

Over the past decade monoclonal antibodies have been successfully employed in a number of animal models of autoimmune disease. We have used antibodies to the class II gene products of the major histocompatibility complex, the CD4 molecule on helper T cells, and the T-cell receptor. Monoclonal anti-class II antibodies have been administered to treat paralytic disease in the animal model of multiple sclerosis--experimental allergic encephalomyelitis. These antibodies not only reverse acute paralytic disease but also decrease the number of relapses in a model of relapsing/remitting multiple sclerosis when given after the first attack. The advantage of this form of therapy is that it is haplotype specific. In other words, in a heterozygous individual it is possible to block the major histocompatibility gene associated with disease susceptibility while leaving other major histocompatibility gene products free for antigen presentation. Thus, animals given this form of immunotherapy are not significantly immunosuppressed. Antibodies to the CD4 molecule have been equally effective in treating animal models of autoimmunity. We and others have reversed ongoing paralysis in experimental autoimmune encephalomyelitis. Relapses have been diminished after the administration of anti-CD4. Antibodies to CD4 have been used successfully to treat animal models of systemic lupus erythematosus, rheumatoid arthritis and myasthenia gravis. Recent trials with anti-CD4 have been successful in the treatment of rheumatoid arthritis and cutaneous T-cell lymphoma. The latter trial employed a chimeric human/mouse antibody. Antibodies to the variable region of the T-cell receptor have been employed to treat experimental autoimmune encephalomyelitis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The use of monoclonal antibodies for treatment of autoimmune disease. 208 87

In vivo therapy with monoclonal antibody (mAb) GK1.5, which recognizes a glycoprotein antigen designated L3T4 on murine helper T lymphocytes, either prevented or suppressed the development of murine lupus, autoimmune encephalomyelitis, and collagen arthritis. The L3T4 antigen in the mouse is analogous to the human Leu-3/T4 antigen expressed on helper T lymphocytes, because they both participate in the T cell response to class II major histocompatibility complex (MHC) antigens. Class II MHC genes and I-A antigens mediate murine experimental autoimmune myasthenia gravis (EAMG) induced by acetylcholine receptor (AChR) autoimmunity. We studied the efficacy of mAb GK1.5 as an immunotherapeutic agent for murine EAMG. Therapy with mAb GK1.5 not only suppressed established autoimmunity to AChR but also prevented loss of muscle AChR in mice with EAMG. Moreover, permanent remission of clinical muscle weakness was induced if mAb GK1.5 therapy was initiated after the onset of clinical disease. Because the function of the Leu-3/T4 determinant on human helper T lymphocytes is analogous to the murine L3T4 determinant, use of antibody to the Leu-3/T4 determinant as an immunotherapeutic agent may provide a way to control the progression of human MG.
 ...
PMID:Immunotherapy for myasthenia gravis: a murine model. 241 35


1 2 3 4 5 6 7 8 9 10 Next >>