Effect Of Myelin Basic Protein Research Articles

Paired and partial correlations of immune parameters of neuro-immuno-test and coagulation parameters of thrombodynamics test in children with children's autism

To reveal paired and partial correlations of values of neuro-immuno-test and thrombodynamics test in children with childhood autism and schizophrenia in childhood in a state of exacerbation. The study used a database of children with childhood autism, obtained by us in 2028-2019. The study included 46 patients with childhood autism (CA) aged 2 to 13 years: median age [Q1; Q3] - 5 years [4; 7], 10 girls (22%) and 36 boys (78%)). The thrombodynamics test (TD) was performed on a T-2 thrombodynamics analyzer according to the manufacturer's instructions. It was shown that there is a statistically significant positive correlation (R=0.369, p=0.018) between the acquired immunity parameter: the level of serum antibodies to myelin basic protein (BMP): abBMP parameter, and the main parameter of platelet hemostasis - the time of appearance of spontaneous clots (Tsp). It can be assumed that autoantibodies to BMP block the procoagulant effect of myelin basic protein and thus have an anticoagulant effect. However, this analysis did not take into account the possible effects of other parameter of the neuro-immuno-test and thrombodynamics test. Therefore, when studying the correlation of specific parameters of the neuro-immuno-test and thrombodynamics, it is necessary to take into account the possible modifying effect of other parameters of these tests. It was shown that after subtracting the influence on the main correlation (abBMP & Tsp) of individual thrombodynamic parameters (Vi, V and D), as well as their total influence, the partial correlations become statistically insignificant. This indicates that these TD parameters can, individually or in total, determine the revealed correlation between the levels of antibodies to the basic myelin protein (Basic Myelin Protein) and the time of the appearance of spontaneous clots. Thus, it was shown that the correlations between the studied parameters of the neuro-immuno-test and the indicators of the thrombodynamics test mutually depend on the other indicators of these tests. This confirms the hypothesis that the immune system and the hemostatic system are two different sides of a single supersystem.

A thermodynamic analysis of the effects of myelin basic protein (MBP) on DPPS and DPPG monolayers

Myelin basic protein (MBP) relate to multiple sclerosis, experimental cerebral spinal cord inflammation and other diseases of the central nervous system. It has important biological significance for the study the diseases which related to the interaction between myelin basic proteins (MBP) and DPPS, DPPG. In this paper, we studied the interaction between molecules at the air/water interface by thermodynamic method and atomic force microscopy (AFM). Experiments show that the average molecular area increases when the protein is incorporated into lipid monolayer. By means of analyzing surface pressure-mean molecular area (π-A) curves, a linear mass conservation plot (i.e. protein amount vs. a matching amount of lipids) was obtained. In addition, the protein partition coefficient and the mixing ration between protein and lipid were calculated. When the surface pressure of the monolayer was 10mN/m, one MBP molecule could be combined with (58±4) DPPS and (37±6) DPPG molecules. The interaction between MBP and DPPG (or DPPS) to determine the nervous system of the disease has a good biophysical significance and medical value.

Effect of myelin basic protein on membrane lipid monolayers composed of DPPC and DPPE molecules

By analyzing the Langmuir monolayer surface pressure-mean molecular area ( π -A) curves, the interaction between myelin basic protein (MBP) and dipalmitoylphosphatidyl-choline cell membranes (DPPC) and dipalmitoylphosphatidylethanolamine (DPPE), which are the different head group of lipid molecules, has been systematically studied, respectively. The results showed that: (1) with the MBP concentration in subphase increasing, the isotherm of DPPC and DPPE monolayer moved to lager average molecular area direction when the number of the lipid on the interface was constant; (2) when the surface pressure of the monolayer reached to 10 mN/m, one MBP molecule could combined with (140 ± 3) DPPC and (100 ± 3) DPPE molecules, respectively; as the surface pressure increased, the number of proteins interacted with two kinds of phospholipid molecules inserting the interface decreased; (3) with the increase of protein concentration, the monolayer film formed by the lipid molecules becomes more loose and MBP molecules are easy to insert into DPPE with smaller head; (4) the π-T curves indicated that the presence of protein could make DPPC monolayer surface pressure decreased, and the higher the concentration of protein was, the more for decreasing values of the surface pressure. Then the DPPC was brought into the MBP subphase; (5) for DPPE monolayer, the protein combined with DPPE inserted the membrane interface, causing the increase of surface pressure, and the higher the protein concentration was, the greater change the pressure appeared.

Ophthalmopathology in rats with MBP-induced experimental autoimmune encephalomyelitis

Multiple studies indicate that T-cells play a major role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, but recently an involvement of antibodies has also been discussed. The aim of our study was to examine the effects of myelin basic protein (MBP) immunization on survival of neurons, alteration of antibody reactivity, and microglia in the retinal ganglion cell layer. EAE was induced in rats by immunization with MBP. Intraocular pressure (IOP) measurements and funduscopies were performed regularly. Neuron cell density was evaluated on cresyl-stained retinal flatmounts. IgG antibody deposition and activated microglia were detected in retina and optic nerve sections via immunohistology. The intensity of autoreactive IgG antibodies was quantified in successive serum samples via tissue arrays. Significant loss of neurons was detected 6weeks after immunization (p < 0.05). At the same time, IgG antibody deposits accumulated in the retina and the optic nerve of EAE animals and a significant microglia turn-over to activation was observed. The level of IgG antibody reactivity against retina and optic nerve tissue continuously increased (p < 0.05). While clinical parameters indicated typical EAE progression, we observed no changes in IOP (p > 0.9) or abnormalities in fundi. Immunization with MBP not only causes neuron loss in the retinal ganglion cell layer, but also triggers antibody reactivity against ocular tissue. Possibly some of these antibodies are involved in the induction of neuronal apoptosis. This study suggests that, apart from T-cell mediation, alteration of antibody reactivity and activated microglia do also influence the ocular pathomechanisms in the EAE model.

The effect of myelin basic protein on the protease inhibitors alpha 1 antitrypsin and alpha 2 macroglobulin.

The effect of myelin basic protein (MBP) of central nervous tissue on the protease inhibitors, alpha 1 antitrypsin (a1AT) and alpha 2 macroglobulin (a2M) was studied in vitro. For this purpose, 2 characteristics of the protease inhibitors were used, viz. their pattern after isoelectric focusing and their trypsin-binding capacity. Both features of purified a2AT disappeared in the presence of MBP. The tests with a2M revealed that the formation and stability of the complex between a2M and protease were reduced. The results of this study suggest that MBP causes an increase in proteolytic activity by inactivating protease inhibitors. The potential relevance of these results for demyelinating processes in man and animal is discussed.

Protein–membrane interaction: effect of myelin basic protein on the dynamics of oriented lipids

We have studied the effect of physiological amounts of myelin basic protein (MBP) on pure dimyristoyl l-α-phosphatidic acid (DMPA) oriented membranes. The investigation has been carried out using several complementary experimental methods to provide a detailed characterization of the proteo-lipid complexes. In particular, taking advantage of the power of the quasi-elastic neutron scattering (QENS) technique as optimal probe in biology, a significant effect is suggested to be induced by MBP on the anisotropy of lipid dynamics across the liquid–gel phase transition. Thus, the enhancement of the spatially restricted, vertical translation motion of DMPA is suggested to be the main responsible for the increased contribution of the out of plane lipid dynamics observed at 340 K.

Suppression of ongoing experimental allergic encephalomyelitis (EAE) in Lewis rats: synergistic effects of myelin basic protein (MBP) peptide 68-86 and IL-4.

Mucosal myelin autoantigen administration effectively prevented EAE, but mostly failed to treat ongoing EAE. Patients with multiple sclerosis (MS), for which EAE is considered an animal model, did not benefit from oral treatment with bovine myelin. We anticipated that autoantigen, administered together with a cytokine that counteracts Th1 cell responses, might ameliorate Th1-driven autoimmune disease, and that nasal administration might considerably reduce the amounts of antigen + cytokine needed for treatment purposes. Lewis rats with EAE actively induced with myelin basic protein peptide (MBP 68-86) and Freund's complete adjuvant (FCA), received from day 7 post-immunization, i.e. after T cell priming had occurred, 120 microg MBP 68-86 + 100 ng IL-4 per rat per day for 5 consecutive days. These rats showed later onset, lower clinical scores, less body weight loss and shorter EAE duration compared with rats receiving MBP 68-86 or IL-4 only, or PBS. EAE amelioration was associated with decreased infiltration of ED1+ macrophages and CD4+ T cells within the central nervous system, and with decreased interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) and enhanced IL-4, IL-10 and transforming growth factor-beta (TGF-beta) responses by lymph node cells. Simultaneous administration of encephalitogenic peptide + IL-4 by the nasal route thus suppressed ongoing EAE and induced IL-4, IL-10 and TGF-beta-related regulatory elements.

Administration of myelin basic protein synthetic peptides to multiple sclerosis patients

A double blind Phase 1 clinical research project was conducted in vivo in multiple sclerosis (MS) patients to determine the effect of myelin basic protein (MBP) synthetic peptides on free (F) and bound (B) titers of anti-MBP in cerebrospinal fluid (CSF). Intrathecal administration of peptide MBP75–95, either as a single dose, or as repeated injections for periods up to 10 weeks, produced complete binding-neutralization of F anti-MBP with no change in B levels. A control peptide MBP35–58 had no effect on F and B anti-MBP levels. Intravenous administration of MBP75–95 resulted in significant decline of F and B CSF anti-MBP levels over a period of one month. Administration of MBP synthetic peptides to MS patients either intrathecally or intravenously did not have any adverse neurological effects and systemic complications did not occur. The MBP epitope for MS anti-MBP was further localized to an area between Pro85 and Pro96.

Regulation of neuronal nitric oxide synthase by histone, protamine, and myelin basic protein

We examined the effects of endogenous basic proteins rich in the amino acid L-arginine on neuronal NO synthase activity by monitoring cyclic GMP formation in intact neuron-like neuroblastoma N1E-115 cells. Histone, protamine and myelin basic protein significantly stimulated cyclic GMP formation, both in a time- and concentration-dependent manner. These effects were blocked by hemoglobin and NO synthase inhibitors. Removal of the extracellular/intracellular Ca2+ gradient by a Ca2+ chelator completely abolished the cyclic GMP responses elicited by histone and protamine, suggesting that influx of extracellular Ca2+ might be involved in their activation of NO synthase. The effects of myelin basic protein on cyclic GMP formation, however, appeared to be due to Ca2+ release from intracellular stores. In cytosolic preparations of rat cerebellum, these basic proteins inhibited the metabolism of L-arginine into L-citrulline by NO synthase. We conclude from our findings that endogenous basic proteins might be involved in the regulation of neuronal NO synthase activity. Their effects on the enzyme could be either stimulatory or inhibitory, depending on whether the basic proteins exert their effects extracellularly or intracellularly, respectively.

Concerted modulation by myelin basic protein and sulfatide of the activity of phospholipase A2 against phospholipid monolayers.

The effect of myelin basic protein (MBP) on the activity of phospholipase A2 (PLA2, EC 3.1.1.4) against monolayers of dilauroylphosphatidylcholine (dlPC) or dilauroylphosphatidic acid (dlPA) containing different proportions of sulfatide (Sulf) and galactocerebroside (GalCer) was investigated. MBP was introduced into the interface by direct spreading as an initial constitutive component of the lipid-protein film or by adsorption and penetration from the subphase into the preformed lipid monolayers. The effect of MBP on PLA2 activity depends on the type of phospholipid and on the proportion of MBP at the interface. At a low mole fraction of MBP, homogeneously mixed lipid-protein monolayers are formed, and the PLA2 activity against dlPC is only slightly modified while the degradation of dlPA is markedly inhibited. This is probably due to favorable charge-charge interactions between dlPA and MBP that interfere with the enzyme action. The PLA2 activity against either phospholipid is increased when the mole fraction of MBP exceeds the proportion at which immiscible surface domains are formed. GalCer has little effect on the modulation by MBP of the phospholipase activity. The effect of Sulf depends on its proportions in relation to MBP. The individual effects of both components balance each other, and a finely tuned modulation is regulated by the interactions of MBP with Sulf or with the phospholipid.

Myelin basic protein stimulates insulin and glucagon secretion from rat pancreatic islets in vitro and in vivo

The effect of myelin basic protein on insulin and glucagon secretion from rat pancreatic islets was studied in vivo and in vitro. The myelin basic proteins isolated from bovine, human and rat brains all stimulated insulin secretion in a similar fashion. In a static incubation of isolated pancreatic islets, myelin basic protein at doses of 15.6-250 micrograms in a 0.5-ml reaction volume (1.7 X 10(-6) to 2.7 X 10(-5) M) significantly stimulated hormone release. Maximal stimulation, obtained at the 250-micrograms dose, was 6.5-fold greater than control for insulin secretion and 6.7-fold greater than control for glucagon secretion. In the case of glucagon no saturation was observed, but saturation was obvious for insulin release at doses of myelin basic protein of 62.5-250 micrograms, larger doses causing permeabilization of the islet membranes as indicated by leakage of acid phosphatase. At a 100-micrograms dose the time course of insulin secretion induced by myelin basic protein indicated a fast initial release, and after the first 2 h only a little more insulin was released. At the lower doses of myelin basic protein (11 and 33 micrograms) the secretion rate was nearly constant after the first hour. Significant stimulation of glucagon release by myelin basic protein was seen after 60 min, the rate of release being roughly constant at 33- and 100-micrograms doses thereafter. At the 11-micrograms dose significant stimulation of hormone release was observed only after a 4-h incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction and fusion of unilamellar vesicles containing cerebrosides and sulfatides induced by myelin basic protein

The effects of myelin basic protein on the aggregation, lipid bilayer merging, intercommunication of aqueous compartments and leakage of small unilamellar vesicles of egg phosphatidylcholine containing different proportions of galactocerebroside and sulfatide were investigated. This was performed employing light scattering, absorbance changes and fluorescence assays (resonance energy transfer, Terbium/dipicolinic acid asssay and carboxyfluorescein release). The apposition of membranes rapidly induced by myelin basic protein is enhanced by sulfatide but reduced by galactocerebroside compared to vesicles of egg phosphatidylcholine alone. On the other hand, the presence of either glycosphingolipid in the membrane interferes with the induction by myelin basic protein of lipid bilayer merging, subsequent fusion and changes of the membrane permeability. Our results support an important modulation by sulfatide and galactocerebroside on the interactions among membranes induced by myelin basic protein, depending on the relative proportions of the glycosphingolipids and phosphatidylcholine.

Restricted lateral diffusion of acidic lipids in phospholipid vesicles aggregated by myelin basic protein

The effect of myelin basic protein on the lateral diffusion of spin-labelled stearic acid in dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) vesicles has been investigated measuring bimolecular collision rates by electron spin resonance spectroscopy. In a molar fraction range of 0.02–0.15, in which the line shape is dominated by the effects of exchange narrowing and dipolar broadening, spectral simulations based on the modified Bloch equations have been used to quantitate the observed spectral changes. Best fitting simulated spectra required a combination of dipole-dipole and spin exchange contributions and least-squares optimizations were applied to obtain a unique combination of these factors. Lateral diffusion coefficients were calculated from collision frequency data in the frame of the lattice model; for pure DMPC and DMPG vesicles lateral diffusion coefficients of 1.7 · 10 −7 and 1.2 · 10 −7 cm s 2 · −1 were obtained. Upon adding myelin basic protein to these vesicles the diffusion coefficients of the negatively charged DMPG decreased to 4.1 · 10 −8 cm 2 · s −1 , whereas that of the zwitterionic DMPC remained unchanged. It is concluded that myelin basic protein must strongly restrict the lateral movement of the DMPG molecules and reduce their diffusion coefficient close to the values observed for proteins. The restricted lateral diffusion is explained by electrostatic interactions which lead to an altered molecular dynamics due to one-to-one lipid exchange and lipid-protein co-diffusion.

Cytotoxic effect of myelin basic protein-reactive T cells on cultured oligodendrocytes

To help clarify effector mechanisms in experimental allergic encephalitis (EAE), the cytotoxic effects of myelin basic protein (MBP)-reactive lymphocytes on oligodendrocytes were studied using a 51Cr release assay. MBP-reactive encephalitogenic T cell lines were cytotoxic to 51Cr-labeled oligodendrocyte target cells derived from Lewis rat fetal brain-dissociated culture, when incubated for 6 h in the presence of antigen-presenting cells (APC) and MBP ( percent 51 Cr release = 65±3% vs. spontaneous release = 22±3% vs. normal lymph node cells + APC and MBP = 20 ± 3%). This reaction is time dependent, likely MHC restricted, and is not just a nonspecific toxic effect against any Lewis target cells since neither fibroblasts nor astrocytes were affected. Other (tetanus toxoid-reactive) lymphoblasts stimulated by specific antigen were not cytotoxic to the oligodendrocytes. These findings suggest that oligodendrocytes might be target cells for MBP-reactive lymphocytes in EAE if antigen presentation is appropriate.

Effect of myelin basic protein on the thermotropic behavior of aqueous dispersions of neutral and anionic glycosphingolipids and their mixtures with dipalmitoylphosphatidylcholine.

The thermotropic behavior of the natural glycosphingolipids galactosylceramide, asialo-Gal beta 1-3GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-4Glc beta 1-Cer (GM1), sulfatide, GM1, NeuAc alpha 2-3Gal beta 1-3GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-4Glc beta 1-1Cer (GD1a), and NeuAc alpha 2-3Gal beta 1-3GalNAc beta 1-4Gal(3-2 alpha NeuAc8-2 alpha NeuAc)beta 1-4Glc beta 1-1 Cer (GT1b), and their mixtures with dipalmitoylphosphatidylcholine (DPPC) in the presence of myelin basic protein (MBP) was studied by high sensitivity differential scanning calorimetry. The transition temperature of DPPC, galactosylceramide, and asialo-GM1 is affected little by MBP while their transition enthalpy is decreased in proportion to the amount of protein in the mixture. The thermotropic behavior of anionic glycosphingolipids is considerably perturbed by MBP. The transition temperature of gangliosides increases in the presence of MBP, whereas that of sulfatide decreases. The enthalpy of the transition of anionic glycosphingolipids increases markedly in the presence of MBP. The excess heat capacity function of these systems can be resolved into two independent phase transitions. Phase separation of enriched lipid/protein domains occurs in a magnitude that depends on the amount of MBP; the rest of the lipid phase exhibits some altered thermodynamic properties. In mixtures of glycosphingolipids with DPPC, phase separation is also present but no phase transition with the characteristic of pure DPPC is found. MBP is changing the properties of the lipid mixture as a whole and does not interact exclusively with the glycosphingolipids. The proportion of MBP required to produce the maximal changes is greater the greater the complexity of the glycosphingolipids polar head group. Relatively small variations of the amount of MBP induce large shifts in the proportion of the different phases present.

Interaction of myelin basic protein and polylysine with synthetic species of cerebroside sulfate

The effect of myelin basic protein on the myelin lipid cerebroside sulfate was studied by differential scanning calorimetry and use of the fatty acid spin label, 16-S-SL, in order to determine (i) the effect of basic protein on the metastable phase behavior experienced by this lipid, and (ii) to determine if basic protein perturbs the lipid packing as it does with some acidic phospholipids. The effects of basic protein on the thermodynamic parameters of the lipid phase transition were compared with those of polylysine which has an ordering effect on acidic phospholipids as a result of its electrostatic interactions with the lipid head groups. Different synthetic species of cerebroside sulfate of varying fatty acid chain length and with and without a hydroxy fatty acid were used. The non-hydroxy fatty acid forms of cerebroside sulfate undergo a transition from a metastable to a more ordered stable state while the hydroxy fatty acid forms remain in the metastable state at the cation concentration used in this study (0.01 M Na + or K +). The non-hydroxy fatty acid forms were still able to go into a stable state in the presence of both basic protein and polylysine. At low concentrations, basic protein increased the rate of the transition to the stable state, while polylysine decreased it for the longest chain length form studied. However, at high concentrations, basic protein probably prevented formation of the stable state. The hydroxy fatty acid forms did not go into the stable state in the presence of basic protein and polylysine. It is argued that the increased rate of formation of the stable state in the presence of basic protein and decreased rate in the presence of polylysine are consistent with interdigitation of the lipid acyl chains in the stable state. Basic protein also had a small perturbing effect on the lipid. It decreased the total enthalpy of the lipid phase transition. When added to the non-hydroxy fatty acid forms it increased the temperature of the liquid crystalline to metastable phase transition and decreased the temperature of the stable to liquid crystalline phase transition. It significantly decreased the transition temperature of the hydroxy fatty acid forms but only a portion of the lipid was affected. In contrast, polylysine increased the transition temperature of the metastable and stable states of all forms of cerebroside sulfate but had a greater effect on the non-hydroxy fatty acid forms than on the hydroxy fatty acid forms. These results suggested that basic protein does not have as great a perturbing effect on cerebroside sulfate as it does on some acidic phospholipids. This reduced perturbing effect is attributed to the participation of cerebroside sulfate in intermolecular hydrogen bonding interactions.

The effect of myelin basic protein on the endogenous phosphorylation of platelets.

Bovine myelin basic protein (BP) induced a shape change and endogenous phosphorylation of a 45,000 (45K) molecular weight protein of intact human platelets. This effect occurred rapidly over an effective concentration range of 5-100 microM BP. BP peptides encompassing residues 1-42, 43-88, and 89-169 from the BP molecule of 169 residues, neither induced phosphorylation of platelets nor blocked the effect of intact BP. Subfractionation of disrupted platelets demonstrated the phosphorylated 45K protein in the 100,000 xg supernate. When isolated platelet membranes were used, no BP induced phosphorylation of a 45K protein could be detected. The amino acid composition of the purified, phosphorylated 45K protein differed from those of other known platelet proteins. BP itself was also phosphorylated by an endogenous platelet protein kinase(s) present both in the 100,000 xg supernatant and in the isolated membrane fraction of platelets. These results indicate that the normal or pathological release of BP from myelin may lead to phosphorylation of an internal protein of platelets and possibly other tissue elements with resultant metabolic and functional changes.

Effect of basic protein from human central nervous system myelin on lipid bilayer structure

The effect of myelin basic protein from normal human central nervous system on lipid organization has been investigated by studying model membranes containing the protein by differential scanning calorimetry or electron spin resonance spectroscopy. Basic protein was found to decrease the phase transition temperature of dipalmitoyl phosphatidylglycerol, phosphatidic acid, and phosphatidylserine. The protein had a greater effect on the freezing temperature, measured from the cooling scan, than on the melting temperature, measured from the heating scan. These results are consistent with partial penetration of parts of the protein into the hydrocarbon region of the bilayer in the liquid crystalline state and partial freezing out when the lipid has been cooled below its phase transition temperature. The effect of the protein on fatty acid chain packing was investigated by using a series of fatty acid spin labels with the nitroxide group located at different positions along the chain. If the protein has not yet penetrated, it increases the order throughout the bilayer in the gel phase, probably by decreasing the repulsion between the lipid polar head groups. Above the phase transition temperature, when parts of it are able to pentrate, it decreases the motion of the lipid fatty acid chains greatly near the polar head group region, but has little or no effect near the interior of the bilayer. Upon cooling again the protein still decreases the motion near the polar head group region but increases it greatly in the interior. Thus, the protein penetrates partway into the bilayer, distorts the packing of the lipid fatty acid chains, and prevents recrystallization, thus decreasing the phase transition temperature. The magnitude of the effect varied with the lipid and was greatest for phosphatidic acid and phosphatidylglycerol. It could be reversed upon cooling for phosphatidylglycerol but not phosphatidic acid. The protein was only observed to decrease the phase transition temperature of phosphatidylserine upon cooling. It had only a small effect on phosphatidylethanolamine and no effect on phosphatidylcholine. Thus, the protein may penetrate to a different extent into different lipids even if it binds to the polar head group region by electrostatic interactions.

The effect of myelin basic protein (MBP) on the bioelectric activity of spinal cord and cerebellar neurones

The effects of myelin basic protein (MBP) on the ventral root response in rat spinal cord in situ and on the spontaneous bioelectric activity of cultured rat Purkinje cells were investigated. Injection of 2 or 4 μl MBP (10 −4 M/l) into the motoneurone pool reduced the ventral root response to dorsal root stimulation. The depression was long-lasting (30–50 min) and partially reversible. At 5 × 10 −6 M/l MBP abolished the spontaneous activity of most cultured Purkinje cells, an effect which was not blocked by haloperidol, propranolol, phenoxybenzamine and bicuculline. The EC 50 for the depression was 4 ± 1 × 10 −6 M/l.

Treatment of experimental allergic encephalomyelitis with encephalitogenic basic proteins.

SummaryThe therapeutic effect of myelin basic protein on established EAE, reported for actively immunized guinea pigs by Alvord et al., has been extended to rats with clinical signs of EAE produced by active sensitization or passive transfer. Furthermore, there was evidence of a limited degree of species specificity inasmuch as rat or guinea pig basic proteins were more effective than monkey basic protein in treating EAE produced with rat spinal cord and adjuvants. However, monkey basic protein appeared to be a fully effective therapeutic agent when EAE was produced with monkey spinal cord. The present work derives importance from current interest in treating patients with multiple sclerosis with basic protein or substances derived from basic protein. The experiments described herein provide a basis for further investigation, in which therapeutic gains can be measured by clinical signs, mortality and histological scoring after only 1 to 3 treatments and in as short a time as 2 days.