Biomedical subjects
Publications and source records attributed to T Fog.
Peripheral blood lymphocytes from 23 out of 27 (85%) patients with multiple sclerosis responded to MS brain homogenates by increased formation of active E-rosettes. Lymphocytes from only six out of 78 (8%) patients with other neurological diseases responded to MS brain homogenates. The possible value of the test in the diagnosis of MS is discussed.
The present study was devoted to an immunochemical elucidation of antigenic similarities and differences between cytoplasmic and microsomal fractions of six multiple sclerosis (MS) and seven non-MS brain autopsy specimens. The antigenic composition of the samples studied was traced by crossed immunoelectrophoresis using antibodies made by immunization of rabbits with the corresponding fraction. The following data were obtained: 1. A measles antigen (defined as an antigen formed in vero cells during measles infection) and two specific antigens have been purified more than 3000-fold from MS brains by means of molecular filtration and DEAE cellulose chromatography. 2. All three antigens have a molecular weight between 10(5)-10(6) daltons and isoelectric points between 3.5-6.0. 3. Measles antigen has also been found in three out of seven non-MS brains, however, it did not stimulate antibody formation in rabbits in contrast to measles antigen of MS brain. The significance of the above-mentioned data is discussed in view of the immunological abnormalities previously found in MS patients. It cannot be excluded that the antigens found represents one or more viral antigens.
The IgG-index and acute phase reactants were measured and oligoclonal bands were looked for in 30 patients with clinically definite multiple sclerosis (MS) and were compared with the clinical data. IgG-index was found elevated in 77% against 22% in a comparable material of patients with other neurological diseases. Oligoclonal bands were found in 74 and 17%, respectively. No correlation was found between these parameters and age, duration of illness, disability, coefficient of progression or age of onset. A statistical evaluation defines the specificity, sensitivity and validity of the methods used. CRP could no be demonstrated in 28, the rest had normal values. C3A was normal in all cases, but appeared to be elevated a little with increasing age, and to be positively correlated to the albumin-index, indicative of a defective blood-brain barrier. No correlation was found between CRP, C3A and the clinical data.
In groups of 16 patients with multiple sclerosis, 13 months' double-blind treatment with transfer factor from random normal donors differed from placebo treatment only in producing a temporary restoration of lymphocyte reactivity to measles virus antigen, and did not arrest the degeneration of nerve tissue.
Antigens in MS and non-MS brains were investigated by means of crossed immunoelectrophoresis. Two MS specific antigens were found: a measles antigen which was present in microsomes and cytosole, and an unidentified antigen present only in cytosole.
Cerebrospinal fluid (CSF) was obtained from 50 neurological patients, 26 of whom suffered from multiple sclerosis (MS). Agar gel electrophoresis and determination of anti-measles antibody titre were performed on the CSF samples. The frequency of elevated measles antibody titre was higher among the MS patients than among the patients with other neurological diseases. Furthermore, oligoclonal IgG in CSF occurred more often among the MS patients than among the other neurological patients. An association between high measles antibody titre and the presence of oligoclonal IgG was observed in CSF from both the MS patients and the patients with other neurological diseases. However, the nature of the correlation between occurrence of oligoclonal IgG and high measles antibody titre remains to be explained.
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The lymphocytes from controls, untreated MS and MS patients treated with transfer factor were stimulated with PHA, PWM, PPD, LPS and MA and the increased incorporation of myoinositol into phosphatidylinositides was determined. As compared with controls, the untreated MS patients revealed significantly lower index of stimulation with PHA, LPS, PPD and MA. The response of lymphocytes from MS patients treated with transfer factor was intermediate. No correlation between disease progression and stimulation of inositol incorporation was observed. Analysis of variance showed that the myoinositol test is not applicable in long-term studies to distinguished single subjects, however it is useful to determine differences between MS patients and controls.
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In five patients with definite multiple sclerosis and lack of cell-mediated immunity to measles and parainfluenza virus antigens, various immunological parameters were studied before and during transfer factor treatment. The study showed that cell-mediated immunity to measles virus antigen, as evaluated by the leukocyte migration agarose test, could temporarily be restored, using repeated injections of transfer factor pooled from unselected, normal blood donors.
Investigations were performed on cell cultures derived from patients with multiple sclerosis (MS) in order to trace a possible virus infection as a cause of the disease. Cell cultures were established from one brain autopsy specimen and four lymph node biopsies from MS patients. Lymphocytes from 28 MS patients and six healthy controls were used for fusion or cocultivation experiments, either immediately after isolation or after mixed lymphocyte cultures (MLC). Lysolecithin fusion and cocultivation experiments were made with Vero cells and with, respectively: cultured brain cells, lymph node cells and lymphocytes from MS patients. Electron microscopical examination revealed intranuclear filamentous structures in 5 per cent of the cells in primary cultures of MS brain and lymph node and in control skin organ cultures. Multinucleated cells were found in six out of 19 cocultures of Vero cells and MS lymphocytes preincubated for 2 days at 37 degrees C. The cultures were tested for the presence of viruses, i.e. measles virus and virus producing hemadsorption with human type O and/or guinea pig erythrocytes and virus against which the MS patients showed serum FA-antibodies. No virus antigen could be demonstrated in the cells.
The general immunological capacity of 40 patients with multiple sclerosis has been evaluated with lymphocyte transformation test including both mitogens (PHA and PWM) and antigens (PPD, Candida albicans, Staph. aureus and E. coli). Determination of T and B cells was performed by E-, EAC-rosetting and immunofluorescence for surface immunoglobulins. Compared with the results obtained in 42 normal individuals only minor differences were found.
As a continuation of our previous studies on the synthesis of prostaglandins (PGs) in human thrombocytes, the present study concerns the biosynthesis of PGs in thrombocytes from patients with multiple sclerosis, as this condition has been suggested to be linked to thrombotic and/or thrombocyte abnormalities. It was found that in these patients a statistically decreased synthesis of PGE1, PGE2 and PGF took place compared to the corresponding values in normal subjects. The ratio between PGE1 and PGE2 was, however, unchanged.
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The present study revealed a positive correlation between the degree of disability of MS patients and the rate of incorporation of myo-(2-3-H)inositol into phosphatidylinositol of lymphocytes stimulated with basic protein (BP) and phytohemagglutinin (PHA). No correlation could be found between the response of lymphocytes to measles antigen (MA) and the degree of disability, stage and duration of multiple sclerosis. No correlation could be observed between the response of lymphocytes to the stimulants studied and the duration of the disease.