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Biomedical subjects

A K Lefvert

Publications and source records attributed to A K Lefvert.

At least 145 records · Page 8Linked to original sources
PubMed1987

Characterization of anti-acetylcholine receptor antibody activity in patients with anti-mitochondrial antibodies.

Antibodies binding to the acetylcholine receptor of human skeletal muscle were found in patients with different kinds of anti-mitochondrial antibodies. In patients with primary biliary cirrhosis (PBC), the antibody activity was found in monomeric and pentameric IgM as well as in IgG, whereas patients with other kinds of anti-mitochondrial antibodies had anti-receptor antibodies of predominantly IgG class. Mice transfused with immunoglobulins from patients with PBC showed a reduction of skeletal muscle receptors comparable to that found in mice who had received immunoglobulins from myasthenia gravis (MG) patients. The antibody affinity was of the same order of magnitude in MG and PBC but antibodies with multiple affinities were more common in PBC. In PBC, the anti-receptor antibody associated idiotype repertoire was markedly different from that found in MG.

Animals↗
PubMed1987

Exercise-induced changes in renal function and their relation to plasma noradrenaline in insulin-dependent diabetic children and adolescents.

Exercise-induced changes in renal haemodynamics, water homoeostasis, urinary albumin excretion and their possible relation to plasma noradrenaline were studied in seven insulin-dependent diabetic children and adolescents without signs of autonomic or somatic neuropathy. Six age-matched clinically healthy patients in remission from the minimal change nephrotic syndrome served as controls. The diabetic patients had a higher glomerular filtration rate and effective renal plasma flow and a lower venous plasma noradrenaline level in the basal state. They also had a higher systolic blood pressure compared with the controls. During exercise the diabetic patients showed a less marked reduction in glomerular filtration rate and urinary flow and a greater increase in filtration fraction. Their heart rate increase during exercise was lower. An inverse correlation between the percentage changes in noradrenaline and glomerular filtration rate during exercise was noted solely in the diabetic patients. They also showed a less marked increase in the ratio between potassium and sodium clearances during and 20 min after exercise. Albumin excretion did not differ between the two groups. We suggest that the sympatho-adrenergic effects of exercise on heart rate, renal haemodynamics and water homoeostasis are blunted in our diabetic patients. Hence, signs of impaired sympathetic activity might be disclosed in young diabetic patients with a disease of fairly short duration.

Adolescent↗
PubMed1987

Isolation and characterization of autologous blood mononuclear cells used for auto-infusion together with monoclonal antibodies in tumor treatment.

CO17-1A is a tumor associated antigen on colorectal carcinoma cells. A mouse monoclonal antibody of subclass IgG2A (MAb 17-1A) has been previously produced against the antigen for therapy. In a phase II study in patients with metastasizing colorectal carcinomas, leukapheresis was performed and isolated cells armed in vitro with MAb 17-1A. The mixture of MAb 17-1A and cells were infused into the patients. The aim of this procedure was to increase the number of cytotoxic cells in the tumor lesion. Two cell purification techniques (A and B) using an IBM 2991 Blood Cell Processor are described. Procedure B gave the highest yield of mononuclear cells (7.52 x 10(9) vs 5.17 x 10(9), p less than 0.01) as well as significantly higher total numbers of monocytes and NK cells. The relative ADCC activity of the two cell isolates were similar. A positive correlation between the frequency of Leu-M5+ cells (monocytes) and 51Cr release was observed. Increasing amounts of OKM1+ (CD11) cells suppressed ADCC. 35-40% of the cells bound MAb 17-1A after 1h incubation at room temperature. There was no substantial increase in cells binding MAb 17-1A upon further incubation. A strong positive correlation between the numbers of monocytes and cells binding MAb 17-1A was seen but also B lymphocytes, T lymphocytes and NK cells bound MAb 17-1A. More than 97% of the added MAb was unbound.

Antibodies, Monoclonal↗
PubMed1987

Cellular production of antibodies related to the acetylcholine receptor in myasthenia gravis: correlation with clinical stage.

Spontaneous and pokeweed mitogen-induced production of specific autoantibodies were studied in cultures of peripheral blood mononuclear cells from patients with different clinical stages of myasthenia gravis. Receptor antibody-related idiotypes and anti-idiotypic antibodies were defined by binding to mouse monoclonal anti-idiotypic and anti-receptor antibodies, respectively. Patients with severe disease had a more complete spectrum of idiotypes in serum, and cells from such patients spontaneously produced more antibody species and higher concentration of both idiotypes and anti-idiotypes than patients with mild disease. The frequencies of antibody specificities in tissue culture supernatants more closely reflected disease activity than those in serum. Tissue culture for the study of different species of autoantibodies has proved to be a useful tool for monitoring the disease and the effects of treatment.

Adult↗
PubMed1987

Idiotypic network in myasthenia gravis demonstrated by human monoclonal B-cell lines.

Human monoclonal anti-receptor and anti-idiotypic antibodies were obtained from Epstein-Barr virus-transformed lymphoblastoid cells of patients with myasthenia gravis. The majority of antibodies (85/117) were IgM, and all IgM antibodies had lambda light chains. A marked restriction to one recurrent idiotype was found, despite the additional presence of other idiotypes in the serum from all patients. The presence of idiotypes and anti-idiotypes in the same patient was verified by the demonstration of specific complex formation between an anti-receptor antibody and an anti-idiotypic antibody produced by two different clones. Studies of human monoclonal antibodies produced by lymphoblastoid cell lines provide important information about the B-cell repertoire in myasthenia gravis and demonstrate a basis for a functional antibody network in this disease.

Antibodies, Monoclonal↗
PubMed1986

Acetylcholine receptor antibodies and anti-idiotypic antibodies produced in blood lymphocyte cultures from patients with myasthenia gravis.

The production of acetylcholine receptor antibody idiotypes and of antibodies directed against receptor antibody idiotopes were studied in cultures of blood mononuclear cells from 11 patients with myasthenia gravis and 11 healthy donors. The antibody specificities were defined by their reaction with monoclonal anti-receptor and anti-idiotypic antibodies. Cells from eight patients but no controls produced both kinds of antibodies. These antibodies were less frequently found in patients' sera. In no patient were antibody specificities present in serum not detected in cell cultures. It is concluded that the B-cell repertoire of specific autoantibodies is more completely disclosed by analysis of blood cell cultures than by serum antibody determinations. The results suggest an idiotype-anti-idiotype regulation of anti-acetylcholine receptor autoimmunity in myasthenia gravis.

Antibodies↗
PubMed1986

Plasma exchange in myasthenia gravis: effect on anti-AChR antibodies and other autoantibodies.

Plasma exchange (PE) was performed in 6 patients with myasthenia gravis (MG). Acetylcholine receptor (AChR) antibodies and other MG-correlated antibodies were quantified each day before, during and after PE. The antibody concentrations decreased during PE with a consisting increase between two exchanges. Repeated PE induced a transient decline in the AChR antibody concentration. The clinical improvement was maximal during the week after PE and correlated in time with increasing concentrations of AChR antibodies.

Adult↗
PubMed1986

Periductal lymphocytic infiltrates in salivary glands in myasthenia gravis patients lacking Sjögren's syndrome.

In eight of eleven patients with clinical and serological evidence of myasthenia gravis (MG), immunohistological analysis of biopsies from labial salivary glands (LSG) showed focal periductal lymphocytic infiltrates, mainly composed of anti-Leu 3a+ T helper lymphocytes, a finding usually regarded as indicative for Sjögren's syndrome (SS). None of the patients could however, according to functional criteria, be considered as having SS. This study thus indicates that lymphocytic infiltrates in LSG can be seen in MG, which has been thought of as an organspecific autoimmune disease with symptoms and signs confined to striated muscles.

Adolescent↗
PubMed1985

IgG production within the central nervous system: a critical review of proposed formulae.

Demonstration of intrathecal IgG production is employed in the diagnosis of various neurological disorders. This pathological IgG fraction in cerebrospinal fluid (CSF) can be visualized directly as oligoclonal bands by electrophoresis or isoelectric focusing or can be calculated as "excess" or "synthesized" IgG according to different formulae. A comparison of the results obtained with isoelectric focusing and with five formulae showed that even though three of the formulae discriminated well between a reference population and patients with multiple sclerosis, all five gave wrong and misleading results in the presence of blood-brain barrier damage, as defined by an abnormally raised CSF/serum albumin ratio. A mathematical and statistical evaluation of the different formulae showed only those based on covariance between CSF/serum IgG and CSF/serum albumin to be valid, and these only when values of CSF/serum albumin were normal. Among the five formulae the IgG index (equal to CSF/serum IgG:CSF/serum albumin) is unique in having a comparatively small and constant maximal relative error resulting from the variation coefficients of the IgG and albumin assays. In the case of blood-brain barrier damage, there exists currently no valid procedure to calculate intrathecally produced IgG; in such instances sensitive electrophoretic or isoelectric focusing methods demonstrating oligoclonal IgG bands are most appropriate to demonstrate intrathecal IgG production.

Adult↗
PubMed1985

Anti-idiotypic antibodies, acetylcholine receptor antibodies and disturbed neuromuscular function in healthy relatives to patients with myasthenia gravis.

Fifty-eight first-degree relatives to 40 patients with myasthenia gravis were investigated regarding presence of acetylcholine receptor antibodies, anti-idiotypic antibodies against the receptor antibodies and clinical and electrophysiological signs of disturbed neuromuscular function. No relative had clinical signs of muscle weakness. The prevalence of low concentrations of receptor antibodies was 54%, of anti-idiotypic antibodies 37% and of pathological and borderline single fibre EMG 45%. No sibling, only 2/11 children and 3/14 parents were normal in all three tests. A combination of receptor antibodies and anti-idiotypic antibodies was the most common finding and was especially frequent in children. In female siblings and children there was a positive correlation between the presence of HLA-antigen A1 and/or B8 and that of receptor antibodies and anti-idiotypic antibodies. Male siblings and children showed no such correlation but had a higher frequency of pathological single fibre EMG than females.

Autoantibodies↗
PubMed1985

Anti-acetylcholine receptor antibodies in primary biliary cirrhosis.

Low concentrations of acetylcholine receptor antibodies were found in 16 out of 17 patients with primary biliary cirrhosis. Seven patients were treated or had been treated with penicillamine. Ten untreated patients had antibody levels corresponding to those found in the treated group. Our data support the presence of receptor antibodies of both IgG and IgM class.

Autoantibodies↗
PubMed1984

Receptor-like activity of a monoclonal anti-idiotypic antibody against an anti-acetylcholine receptor antibody.

A monoclonal anti-idiotypic antibody against an anti-acetylcholine receptor antibody from a patient with myasthenia gravis was shown to bind the cholinergic ligand alpha-bungarotoxin. This binding could be inhibited by other cholinergic ligands, both antagonists and agonists. The anti-idiotype was also able to elicit the production of anti-receptor antibodies in mice. Thus, the anti-idiotype had functional properties similar to those of the original antigen, the acetylcholine receptor.

Animals↗
PubMed1983

Newborn infants to myasthenic mothers: a clinical study and an investigation of acetylcholine receptor antibodies in 17 children.

We studied 17 children born to 15 myasthenic mothers; 2 of the infants had neonatal myasthenia gravis. Pyridostigmine was transferred to the child and accumulated in the amniotic fluid. Sixteen children had receptor antibodies at birth. In the affected infants, the half-life of the receptor antibody concentration was longer than it was in the others. Using an anti-idiotypic antibody, we found marked differences between the idiotypes in the mother and in affected children. Transient synthesis of receptor antibodies in the child seems to be a factor in the pathogenesis of neonatal myasthenia gravis.

Acetylcholine↗