Regional studies of myelin proteins in human brain and spinal cord.

The myelin specific proteins, myelin basic protein (MBP) and myelin proteolipid protein (PLP) were quantitated by radioimmunoassay (RIA) and the activity of the enzyme 2',3'-cyclic 3' phosphohydrolase (CNP) measured, in 27 regions of normal brain and spinal cord. Varying regional concentrations for each protein and regional variations for protein ratios were noted, supporting the concept of a varying chemical composition for myelin throughout the central nervous system (CNS). Variation was also noted among myelin subfractions from a single region. Regions with special sensitivity to the multiple sclerosis process had relatively lower proportions of CNP in several, but not all cases.

Studies of myelin proteins in multiple sclerosis brain tissue.

Using radioimmunoassays (RIA) for the myelin specific proteins, myelin proteolipid protein (PLP) and myelin basic protein (MBP) and an enzyme assay for the activity of the myelin marker enzyme 2'3' cyclic-3' phosphohydrolase (CNPase), we have studied plaque, periplaque and normal appearing white matter (NAWM) tissue. We found that all three mylein proteins are decreased in all regions, including NAWM, of MS brain, with a decreasing gradient from NAWM to perregion. Surprisingly, when the ratios of the proteins were calculated, MBP activity, although decreased was found to be relatively preserved.

Thymectomy-induced decrease in T gamma cells and OKT8+ cells in multiple sclerosis.

Studies were performed on lymphocytes from patients with multiple sclerosis before and after thymectomy (group I) and before and after thymectomy and azathioprine therapy (group II), and from matched control patients with multiple sclerosis, control patients with other neurological diseases, and healthy control subjects. Following treatment the percentage of T gamma cells in both group I and group II patients decreased from above the mean normal control levels to below this level; OKT8+ cell numbers in group I became lower than in any of the control groups; the percentage of concanavalin A-induced suppressor activity, which was initially normal, fell in group II and suggestively but not significantly in group I; and total blood lymphocytes in group I decreased from normal to below control levels. Other tests showed no significant changes with therapy. No significant difference in changes in clinical status were observed after one year in the treated patients compared with matched controls.

Immunoreactive myelin proteolipid, protein-like activity in cerebrospinal fluid and serum of neurologically impaired patients.

Two hundred seventy-eight samples of cerebrospinal fluid and 273 samples of sera from a variety of neurological patients were examined by radioimmunoassay for myelin proteolipid protein-like reactivity as an index of structural damage to myelin. Groups of patients with active central nervous system damage could be distinguished easily, although there was a small percentage of false positive reactions. The reactivity was most marked in the demyelinative, encephalitic, and stroke categories. A radioimmunoassay for proteolipid protein of proper sensitivity and specificity may prove to be a useful objective clinical measure of the presence and degree of disease activity in multiple sclerosis and other diseases.

Studies on the thymus from patients with multiple sclerosis and myasthenia gravis.

The thymus glands which were excised for therapy (myasthenia gravis; MG) or experimental therapy (multiple sclerosis; MS) were compared to thymic biopsies from patients undergoing cardiac surgery. There was no difference in the weight or total cells of MG and MS thymuses or of the cell density of control, of MG or MS glands. Only 1 of 25 MS thymuses was hyperplastic, as were 2 of 9 of the MG thymuses and none of the controls. Several differences were noted for thymic lymphocyte proliferation to mitogenes in MS patients and to antigens in MS and MG patients. Ms thymuses had a decreased stimulation index to antithymocyte globulin and to optimal concentrations of pokeweed mitogen. Myasthenia gravis thymuses showed a significantly increased stimulation of myelin basic protein. The % B and % T cell counts were normal for the MS patients. No differences were noted in the incidence of mixed lymphocyte reactions between thymocytes and peripheral lymphocytes in the three groups. Fresh thymic lymphocytes did not suppress concanavalin A stimulated lymphocyte proliferation. It is not known if the differences in lymphocyte proliferation between MS, MG, and control thymuses represent a primary or secondary change.

Prolonged effects of large-dose methylprednisolone infusion in multiple sclerosis.

Three daily 1-gm doses of methylprednisolone were administered to 12 patients with multiple sclerosis. Granulocytes, lymphocytes, T and B lymphocytes, lymphocyte transformation in response to several mitogens and one antigen, plasma cortisol, and serum IgM and IgA all returned to baseline within a few days. However, total white blood count, unstimulated lymphocyte incorporation of 3H-thymidine, hematocrit, serum IgG, and cerebrospinal fluid IgG synthesis remained altered 1 week after the infusion. The relationship of these changes to any clinical effects is unknown.