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Biomedical subjects

A K Lefvert

Publications and source records attributed to A K Lefvert.

171 records · Page 10Linked to original sources
PubMed1977

Immunoglobulins in myasthenia gravis: effect of human lymph IgG 3 and F (ab')2 fragments on a cholinergic receptor preparation from Torpedo marmorata.

Lymph IgG from patients with myasthenia gravis was shown to inhibit the binding of radio-labelled Naja naja siamensis alpha-neurotoxin to membrane fragments from the electric organ of Torpedo marmorata. This effect could be related to IgG subclass 3 and to the F(ab')2 fragment. These findings confirm the involvement of antibodies of postsynaptic structures in myasthenia gravis.

Animals↗
PubMed1976

Effects of some immunosuppressive procedures on myasthenia gravis.

Clinical Observations. A total of 53 MG patients have been treated with different immunosuppressive methods (alone or combined) with the following effects: Thymectomy was performed in 38 patients. The improvement was excellent in 15, and moderate or uncertain in 20. In three patients severe long-lasting deterioration followed the operation. ACTH treatment (n=32): Initial deterioration during the 5-7 days of heavy ACTH treatment (1000 IU) was followed by an improvement lasting on an average 4 months. The improvement was good or moderate in 78% of the patients. Betamethazone treatment has been tried in six patients where ACTH and azathioprine was ineffective. In four of these patients the results were excellent. Azathioprine treatment has been given to 26 patients for periods up to 7 years. An improvement is measurable after 6-12 weeks and it seems maximal after about 1 year. Of the 26, 80% responded favorable with reduction in the need for cholinesterase inhibitors. Severe complications were seen in three patients with one death. Drainage of thoracic duct lymph was initiated in 14 patients up to 4 weeks with rapid improvement lasting as long as drainage was performed. Long-termed effects of the drainage may be present, however. Retransfusion of homologous cell-free lymph precipitated a return of the myasthenic symptoms. Biochemical Studies on Myasthenic Lymph. Using a membrane preparation from the electric organ from Torpedo marmorata and tritiated Naja naja siamensis neurotoxin we demonstrated a decreasing binding of toxin to the receptor in the presence of MG lymph gamma-globulin fraction. Gammaglobulins from controls showed almost no inhibition of the neurotoxin binding. Immunological Studies. An increased frequency of HL-A1 and 8 was found in female patients. LD typing was also performed. During a period of three weeks of thoracic duct drainage 130X10(9) or about 10% of total number of lymphocytes in the body were removed. In the lymph an initial decrease in the proportion of thymus-derived lymphocytes (T cells) occurred, which was accompanied by a sequent increase in the proportion of bone-marrow-derived lymphocytes (B cells). Towards the end of drainage this effect was reverted. Mitogenic stimulation using lymphocytes from thoracic duct drainage revealed no differences as compared to normal cells. The proportions of T and B cells was studied in the peripheral blood in nine patients treated with ACTH. During treatment there was an initial decrease in the proportion of T cells accompanied by a subsequent rise in the proportion of B cells, which was maximal after 3-10 days. These proportions were reverted to normal 1-5 days after the maximal change. The effect of azathioprine on T and B cells has also been studied.

Adrenocorticotropic Hormone↗
PubMed1975

Practical aspects on the determination of serum alkaline phosphatase isoenzymes using L-phenylalanine and urea.

Simple methods for estimation of the most frequently occurring alkaline phosphatase isoenzymes in serum are evaluated. Methods based on inhibition by L-phenylalanine or denaturation by heat or urea have been adopted for a reaction-rate instrument (LKB 8600) using conditions recommended by the Scandinavian Enzyme Committee, when applicable. The analytical results are directly evaluated for various groups of patients and also used in a mathematical "three-isoenzyme" model. These calculations did not improve the clinical value of the primarily obtained data. Thus, it was concluded that under certain precautions the results obtained in the presence of L-phenylalanine or urea should be used separately.

Alkaline Phosphatase↗
PubMedDate not supplied

Acetylcholine receptor antibodies in the diagnosis of human and experimental myasthenia gravis.

Aspects of acetylcholine receptor immunology and circulating receptor antibodies are reviewed with regard to both human and experimental myasthenia gravis. Receptor antibodies that have negligible cross-reactivity with skeletal muscle receptor can nonetheless cause destruction of the postsynaptic motor endplate area. Antibodies to mammalian skeletal muscle receptor can bind in-situ receptors. Transfer of myasthenic IgG increases neurophysiologic symptoms in rabbits showing slight signs of experimental myasthenia gravis, suggesting a block of in-situ receptors. Determination of receptor antibodies using RIA tests and partially purified human skeletal muscle receptor has been evaluated in the diagnosis of myasthenia gravis. Ninety percent of Swedish myasthenic patients in one study were found to have receptor antibodies. A rough correlation has been found between antibody titer and the severity of disease. Immunosuppressive treatment and thymectomy decrease the titer. In patients with thymoma, high antibody titers remain. When taken together, antibody-titer determination and electrophysiologic tests--particularly single-fiber electromyography--are very valuable diagnostic tools.

Animals↗
PubMedDate not supplied

The clinical significance of HAMA in patients treated with mouse monoclonal antibodies.

Twenty-four patients were analyzed for the development of HAMA (human antimouse antibodies) after being treated with repeated doses (200-500 mg) of the mouse monoclonal antibody (MAb) 17-1A. All patients developed anti-17-1A IgG antibodies, and most of them also developed IgM antibodies. In only two patients could immune complexes be demonstrated. Allergic reactions were rare (1.9%). In an extended study, a further 19 patient were analyzed for an idiotypic response. Forty-one out of 43 patients developed antiidiotypic antibodies (ab2), and 20 of these also anti-anti-idiotypic antibodies (ab3). Ab3+ patients responded significantly better (p = 0.01) and survived longer (p < 0.001) compared to ab3- patients. In this study, we showed that MAb 17-1A could be repeatedly given on a safe basis. The development of high titers of HAMA did not cause significant clinical problems when further repeated infusions of MAb 17-1A were given. The development of an idiotypic response also indicate that the induction of HAMA might be beneficial and not harmful to the patient.

Adult↗
PubMedDate not supplied

The start of an autoimmune disease: idiotypic network during early progression of myasthenia gravis.

Anti-acetylcholine-receptor antibodies of IgG and IgM classes and antiidiotypic antibodies were determined in patients with myasthenia gravis at various times after the start of the disease. Patients with a disease duration of less than one year had a higher prevalence of antiidiotypic antibodies (31/32) than patients who had had the disease for more than 5 years (49/79), and the concentration of antiidiotypic antibodies was also higher in patients with early disease (p less than 0.005). The concentrations of antiidiotypic antibodies decreased during progression of the disease concomittant with an increase in IgG anti-receptor antibodies. A change from IgM to IgG anti-receptor antibody production was also found. In two patients, who developed myasthenia after bone-marrow grafting and who were followed before start of disease, antiidiotypic antibodies appeared before anti-receptor antibodies and before symptoms of myasthenia were present. The high prevalence and concentration of antiidiotypic antibodies in early disease indicate that development and expression of antiidiotypic antibodies are important in early myasthenia gravis.

Age Factors↗
PubMedDate not supplied

Isolation of an antiidiotypic antibody with acetylcholine-receptor-like binding properties from myasthenia gravis patients.

The network theory predicts that a subpopulation within the antiidiotypic (anti-Id) antibody response will be the internal image of the priming stimulus. In myasthenia gravis, a portion of the anti-acetylcholine-receptor (anti-AChR) antibody repertoire is directed against the ligand-binding site. These antibodies would be expected to elicit an "anti-idiotype" which is the internal image of the receptor-binding site and hence may also bind cholinergic ligands. We have utilized this theoretical specificity to isolate anti-Id antibodies with AChR-like ligand-binding properties from the serum of 4 myasthenia gravis patients using a choline affinity column. Affinity-purified antibodies from one patient were characterized and found to exhibit binding properties similar to the AChR for various cholinergic ligands.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

Idiotypic network in myasthenia gravis.

Fluctuations in idiotypic and anti-idiotypic Ab levels over time in two myasthenia gravis patients were found to vary either inversely with one another or in relation to one another. A pair of 46-year-old female twins in which one of the twins developed myasthenia gravis while the other remained healthy were also studied. Ab specificities and immunoglobulin specificities available in the B cell repertoire were found to be similar in both twins.

Adult↗