Histocompatibility antigens in Alzheimer's disease. A preliminary study.

A preliminary study of Alzheimer's disease showed an apparent excess of the antigen A2 in patients who presented the disease before the age of 60, whereas those with onset after 64 showed different frequencies of the antigens A1 and A3 when compared with the local population. There was no abnormality in the distribution of B locus antigens. The findings are briefly discussed.

A common tumour-specific antigen: III. Preparation of small fragments incorporating the cell-sensitizing determinant.

Intact cells of various human tumours and tumour cell lines, and acid extracts of various human tumours and normal tissues, each of which react with the lymphocytes of cancer patients as detected by the macrophage electrophoretic mobility (MEM) test, have been subjected to proteolysis. Activity was destroyed by some enzymes, and the apparent molecular size of the active material was reduced by others. An active low-mol.-wt fragment has been partially purified from papain digests of several tumours. Peptides with normal tissue and tumour-characteristic activities have been separated chromatographically from tryptic digests of tumour extracts.

Linoleic acid therapy in severe experimental allergic encephalomyelitis in the guinea-pig: suppression by continuous treatment.

The effect of oral linoleic acid (LA) treatment on experimental allergic encephalomyelitis (EAE) in guinea-pigs in three trials of differing disease intensity has been investigated. The efficacy of LA treatment was linked to the severity of the disease being suppressed. The trial with the greatest disease severity showed no beneficial effect. The other two trials with less severe disease showed a marked therapeutic response to LA, but only when treatment was started before immunization and given continuously. This was apparent in both clinical and histopathological responses. These results support an immunoregulatory mechanism for LA treatment in EAE and by analogy in multiple sclerosis.

Histocompatibility antigens in Alzheimer's disease. A preliminary study.

A preliminary study of Alzheimer's disease showed an apparent excess of the antigen A2 in patients who presented the disease before the age of 60, whereas those with onset after 64 showed different frequencies of the antigens A1 and A3 when compared with the local population. There was no abnormality in the distribution of B locus antigens. The findings are briefly discussed.

The effect of Cop 1, a synthetic polypeptide, on chronic relapsing experimental allergic encephalomyelitis in guinea pigs.

Cop 1, a synthetic polypeptide, was evaluated for its effect on a chronic relapsing form of experimental allergic encephalomyelitis (EAE). Pretreatment of juvenile Strain 13 guinea pigs with Cop 1 in incomplete Freund's adjuvant (IFA) which were subsequently challenged with guinea pig spinal cord in complete Freund's adjuvant (CFA) had a marked effect in delaying or preventing the appearance of clinical signs of EAE. Administration of Cop 1 on appearance of clinical signs of EAE prevented progression of the first episode of the disease. Although relapses were not always prevented, they were modified on their duration and intensity both clinically and histologically.

T lymphocytes in patients with Down's syndrome.

Individuals with Down's syndrome (DS) are thought to have abnormalities in their immune system, and a tendency to infection and malignancy. Studies to quantify the number of T lymphocytes in the peripheral blood of 82 unselected institutionalized patients (50 DS, 27 controls matched for sex and age, 2 chronic lymphocytic leukemic, 2 acute leukemic, and 1 Hodgkin's disease) were conducted. The numbers of circulating T cells in DS patients did not differ significantly from the control group, and were in the upper limits of normality. Number of "avid" T cells, however, were significantly higher in the DS than in the control group. The blastogenic response of the T cells to mitogen was significantly depressed. The data did not exclude the existence of qualitative abnormalities. Except for DS patients with congenital heart disease, those older than 15 years were not more prone to upper respiratory infections than other institutionalized mentally retarded patients.

Multiple sclerosis-associated agent. Failure of MS brain and serum to depress the polymorph count in normal mice and mice inoculated with cells containing C/type particles.

The groups that originally reported and confirmed the demonstration of a multiple sclerosis associated agent (MSAA) are now, along with others, unable to reproduce this effect. In view of this confusion and the potential importance of this work for multiple sclerosis (MS) we have done a strict double-blind trial using larger groups of mice (10) and counting more cells (900) than in previous reports to offset the high variability of mouse polymorphonuclear neutrophil (PMN) counts. Sera from 5 active MS patients and 4 normal subjects were tested in mice, half of which had previously been injected with PAM line cells (containing C-type particles and subject to reduced cell yield when cultured with MS brain extract). No significant PMN depression was found in either MS or normals on any basis of comparison. However, a significant depression was seen following PAM cell injection irrespective of serum origin. Higher counting accuracy did not reduce PMN variability. A single MS brain specimen was also without effect. consequently we have been unable to confirm the existence of an MSAA as defined by PMN depression in mice.

Circulating antibody to myelin basic protein in relapsing-remitting multiple sclerosis? A comparative group and sequential study by radioimmunoassay.

Sera from multiple sclerosis patients with relapsing-remitting disease and normal subjects were tested for antibody to myelin basic protein by a sensitive radioimmunoassay. The results showed a marginally decreased titre in multiple sclerosis superimposed on a seasonal variation. There was no correlation with the clinical state of the patients. Results are discussed briefly in relation to humoral antibody function in multiple sclerosis and experimental autoimmune encephalitis.

Experimental allergic encephalomyelitis in the guinea pig. Failure to suppress with crude human chorionic gonadotrophin.

A single intraperitoneal dose of 3000 IU of crude human chorionic gonadotrophin (HCG), of proven in vitro immunosuppressive activity, gave only marginal effect on the clinical and histopathological course of experimental allergic encephalomyelitis (EAE) in guinea pigs, which did not reach statistical significance. Treatment 7 and 11 days after immunization significantly reduced the Mantoux reaction concomitant with decreased perivascular inflammation, but with unaltered or (when treated at onset) slightly enhanced clinical disease, with in vitro lymphocyte reactivity increased in accord. Much earlier treatment gave the opposite effect of a marginal improvement. HCG in vitro immunosuppressive potency was dependent on its concentration, intensity of immune response and sequence of addition. While the action of HCG on EAE does not point to an effective therapy for multiple sclerosis, as suggested by the influence of pregnancy on this disease, non-HCG fractions of urine during pregnancy may yet contain highly efficacious immunosuppressants.

Effect of live attenuated vaccines on the course of experimental allergic encephalomyelitis. A pilot study.

The clinical severity of EAE is enhanced by pre-treatment with distemper, measles and BCG vaccine, measles vaccine gives a more severe onset of disease. Rubella vaccine and TAB leads to mild disease which recurs on re-treatment with the appropriate vaccine. These findings and their possible significance in MS are briefly discussed.

Non-specificity of laboratory test for diagnosis of multiple sclerosis.

It has been claimed that the inhibiting effect of linoleic acid on the macrophage electrophoretic mobility test provides a specific laboratory method for the diagnosis of multiple sclerosis (M.S.) and may also enable susceptible relatives of M.S. patients to be identified. Three trials of the method under double-blind conditions have failed to confirm that the test is diagnostically useful.

A common tumour specific antigen. II. Further characterization of the whole antigen and of a cross-reacting antigen of normal tissues.

Experimental evidence supporting the postulated analogy between myelin basic protein and a previously described common tumour specific antigen is summarized under antigenic cross-reactivity, subcellular localization, molecular size, basicity and proteolipid nature. A third protein antigen, present in all tissues, also shows strong similarities in all these respects.

Lymphocyte sensitization to basic protein of brain in multiple sclerosis and other neurological diseases.

The number of lymphocytes in the blood sensitized to encephalitogenic factor (EF) is less in multiple sclerosis than it is in general paralysis of the insane. The number appears related to the extent of parenchymatous destruction. The study offers no support for the view that lymphocyte sensitization to EF is of pathogenetic significance in multiple sclerosis.

Relation of measles virus to encephalitogenic factor with reference to the aetiopathogenesis of multiple sclerosis.

A combination of affinity chromatography with the macrophage electrophoretic migration (MEM) test has been used to study the antigenic similarities between encephalitogenic factor (EF) and measles virus. These have determinant(s) sufficiently closely related to account for the elevated level of circulating antibody to measles in multiple sclerosis.