Incidence of AChR Ab-positive myasthenia gravis in Israel: A population-based study.

Background: The incidence of myasthenia gravis (MG) has traditionally been low, ranging between 2-6/10 . Several recent epidemiological studies have reported a higher incidence. We, therefore, aimed to assess and characterize the incidence of MG in Israel.

Preconditioned mesenchymal stem cells treat myasthenia gravis in a humanized preclinical model.

Myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) Abs is an autoimmune disease characterized by severe defects in immune regulation and thymic inflammation. Because mesenchymal stem cells (MSCs) display immunomodulatory features, we investigated whether and how in vitro-preconditioned human MSCs (cMSCs) could treat MG disease. We developed a new humanized preclinical model by subcutaneously grafting thymic MG fragments into immunodeficient NSG mice (NSG-MG model).

Long-term treatment of multiple sclerosis with glatiramer acetate: natural history of the subtypes of anti-glatiramer acetate antibodies and their correlation with clinical efficacy.

A retrospective phase IV study was designed to evaluate the anti-GA antibody subtypes, test their in vitro neutralizing activity and correlate these parameters with the clinical efficacy, in long-term GA treatment of MS patients. Serum samples from 153 MS patients, 126 treated with GA for 2 to 15 years (mean 6.6 years) and 27 treated for <2 years, were collected.

Immunosuppression of EAMG by IVIG is mediated by a disease-specific anti-immunoglobulin fraction.

Intravenous immunoglobulin (IVIG) administration has been beneficially used for the treatment of a variety of autoimmune diseases including myasthenia gravis (MG). We have demonstrated that IVIG administration in experimental autoimmune MG (EAMG) results in suppression of disease that is accompanied by decreased Th1 cell and B cell proliferation. Chromatography of pooled human immunoglobulins (IVIG) on immobilized IgG, isolated from rats with EAMG or from MG patients, results in a depletion of the suppressive activity of the IVIG.

A disease-specific fraction isolated from IVIG is essential for the immunosuppressive effect of IVIG in experimental autoimmune myasthenia gravis.

Intravenous immunoglobulin (IVIG) treatment is beneficially used in autoimmune disorders including myasthenia gravis (MG) although its mode of action and active components are still not fully identified. In an attempt to isolate from IVIG a disease-specific suppressive fraction, IVIG was passed on columns of IgG from rats with experimental autoimmune MG (EAMG) or from MG patients. These chromatographies resulted in depletion of the suppressive activity of IVIG on rat EAMG whereas the minute amounts of IgG fractions eluted from the EAMG- or MG-specific columns retained the immunosuppressive activity of IVIG.

Anti-inflammatory properties of cholinergic up-regulation: A new role for acetylcholinesterase inhibitors.

We investigated the anti-inflammatory effects of acetylcholinesterase inhibitors (AChEI) at the cellular and molecular levels. AChEI suppressed lymphocyte proliferation and pro-inflammatory cytokine production, as well as extracellular esterase activity. Anti-inflammatory activity was mediated by the alpha7 nicotinic acetylcholine receptor (neuronal); the muscarinic receptor had the opposite effect.

A synthetic heparin-mimicking polyanionic compound inhibits central nervous system inflammation.

The immunomodulating capacity of heparin led us to test the effect of the synthetic heparin-mimicking and low anticoagulant compound RG-13577 on the course of experimental autoimmune encephalomyelitis (EAE) and central nervous system (CNS) inflammation. EAE was induced in SJL mice by inoculation with whole mouse spinal cord homogenate. RG-13577, delivered intraperitoneally, inhibited the clinical signs of acute EAE and markedly ameliorated inflammation in the spinal cord, primarily by inhibiting heparanase activity in lymphocytes and astrocytes and thus impairing lymphocyte traffic.

Inhibitory effect of carbamazepine on inflammatory mediators produced by stimulated glial cells.

Exposure of rat glial cells to lipopolysaccharide (LPS) induces the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)), the inflammatory mediators implicated in the pathogenesis of seizures and epilepsy. To determine the effect of the anticonvulsant drug carbamazepine (CBZ) on the inflammatory process, LPS-stimulated rat primary glial cultures were exposed to this agent. Dose-dependent inhibition of NO and PGE(2) production was observed of up to 77 and 88%, respectively.

Suppression of experimental autoimmune encephalomyelitis by tyrphostin AG-556.

Tyrosine kinase blockers from the AG 126/AG-556 tyrphostin family are shown to inhibit the lipopolysaccharide (LPS)-induced production of tumor necrosis factor alpha (TNFalpha), nitric oxide (NO), and prostaglandin E2 (PGE2) in primary rat astrocytes cultures. The tyrphostin AG-556 which was previously shown to be effective against sepsis in mice and dogs also show excellent efficacy in inhibiting experimental autoimmune encephalomyelitis (EAE) in mice. AG-556 does not block the activation of JNK/SAPK and of p38/HOG and therefore seems to act at a target down stream to these kinases which is activated in stress or at a target on an obligatory parallel pathway.

Effect of sphingosine on rat glial cells: inhibition of prostaglandin E2 and insensitivity of nitric oxide generation.

The effect of sphingosine on lipopolysaccharide (LPS)-mediated protein kinase C (PKC) activation and prostaglandin E2 (PGE2) and nitric oxide (NO) production was studied in primary cultures of rat glial cells. Incubation of cells with LPS elicited translocation of PKC from the cytosolic to the membranous compartment, as shown by measuring PKC activity and by immunoblotting. Under these conditions, a sustained increase in both PGE2 and NO production was measured.

Immunomodulation of experimental autoimmune myasthenia gravis with linomide.

Linomide, a synthetic immunomodulator, increases natural killer (NK) activity and markedly activates several lymphocyte populations in both experimental animals and humans. It has been shown to ameliorate the autoimmune manifestations of lupus-like disease in MRL/lpr mice and the clinical and pathological signs of acute and chronic-relapsing experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. We examined the effect of linomide (100 mg/kg/day; administered in drinking water) on rabbits and rats with experimental autoimmune myasthenia gravis (EAMG).

Variable effect of calcium channel blockers on the decremental response in experimental autoimmune myasthenia gravis.

We tested the effect of intravenous administration of verapamil and nimodipine on the decremental response in rabbits with experimental autoimmune myasthenia. Nimodipine produced an immediate augmentation of the decremental response to 3-Hz nerve stimulation, which lasted about 30 min. In contrast, verapamil caused marked amelioration of the decrement beginning 30 min after injection.

Synthesis of antibodies against measles virus and myelin by in vitro stimulated B-cells derived from patients with subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) patients carry persistent measles virus infection in the brain. Furthermore, the blood lymphocytes contain viral RNA. Lymphocytes derived from 6 SSPE patients were stimulated with Epstein-Barr virus (EBV).

Inhibition by alpha-fetoprotein fractions of hemagglutination reactions between A and B antigens of human red blood cells and specific antisera.

It is shown that fetal alpha-fetoprotein (AF)-rich fractions, isolated by chemical methods, can inhibit the agglutination reaction of human AB red blood cells (RBC) with specific antisera. Hemagglutination was not inhibited by other amniotic fluid or umbilical cord serum proteins in equivalent concentrations or by other pregnancy-associated hormones. The inhibitory effect is related to the amount of antibodies and AF fractions.