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Biomedical subjects

A K Lefvert

Publications and source records attributed to A K Lefvert.

At least 127 records · Page 7Linked to original sources

A longitudinal study of class and subclass antibody response to pneumococcal vaccination in splenectomized individuals with special reference to patients with Hodgkin's disease.

Antibody class and subclass response to pneumococcal vaccination was monitored in 173 splenectomized individuals. The distribution according to indication for splenectomy was Hodgkin's disease (HD; n = 41), non-Hodgkin lymphoma (NHL; n = 25), autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (n = 17), accidental splenectomy during abdominal surgery for malignant (AMA; n = 15) and benign (ABE; n = 42) disease and splenectomy due to splenic rupture caused by trauma (TRAUMA; n = 33). Pre-vaccination total IgG pneumococcal antibody values (i.e. against the whole antigen = the vaccine) in the NHL patients were lower than in the ABE and TRAUMA groups (p less than 0.05). The response to vaccination in HD and NHL patients did not differ from that in the other patient groups. Furthermore, pre-vaccination values did not differ between HD patients vaccinated before splenectomy and treatment and those vaccinated after, although the former group showed a better response to vaccination (p less than 0.05). HD and TRAUMA patients were followed by serial serum sampling. The antibody values declined to pre-treatment levels after 3 years but no differences either between HD and TRAUMA patients or between HD patients vaccinated before or after splenectomy and treatment were observed with regard to antibody decrease. It is concluded that pneumococcal antibody levels increased in all splenectomized patient groups following vaccination. The pattern of the antibody decline motivates revaccination studies in patients 2 yr post-immunization.

Adult↗

Evidence of a local immune activation in cystic brain tumors.

The fluid of cystic brain tumors was characterized with regard to the protein content. In most malignant tumors, the concentrations of immunoglobulins G and M (IgG and IgM) were higher relative to other proteins in the cyst fluid than in the serum of the same patient. A markedly elevated ratio of monomeric to pentameric IgM was detected in the cyst fluid of two patients with glioblastomas. The results indicate a local immunoglobulin synthesis in malignant cystic brain tumors. It is hypothesized that higher-than-expected concentrations of IgG and IgM in cyst fluid as compared to plasma are a sign of an ongoing immune response triggered by the tumor.

Adolescent↗

B cell and autoantibody repertoire in a pair of monozygotic twins discordant for myasthenia gravis.

A pair of identical twins, 47 years of age, who have been discordant for myasthenia gravis for 15 years were studied with regard to clinical status, neuromuscular function, and presence and properties of myasthenia specific autoantibodies. The autoantibody repertoire was tested in serum, as produced by peripheral lymphocytes in culture and as revealed by B cell lines. The healthy twin had no clinical signs of myasthenia and no signs of impaired neuromuscular function on electrophysiological tests. The autoantibody repertoire and the avidity of the anti-receptor antibodies were similar in both individuals. Epstein-Barr virus transformation of peripheral lymphocytes revealed a higher incidence of B cells committed to make autoantibodies in the healthy twin than in her myasthenic sister.

Antibody Affinity↗

Anti-idiotypic B-cell lines from a patient with monoclonal gammopathy of undetermined significance.

The B-cell repertoire in a patient with benign monoclonal gammopathy of unknown significance was studied using Epstein-Barr virus transformation of peripheral lymphocytes. The presence of anti-idiotypic B cells producing monoclonal antibodies that reacted with idiotypic determinants on the monoclonal immunoglobulin was verified. The two monoclonal anti-idiotypic antibodies studied were of the IgM-kappa type. Such anti-idiotypic antibodies may be part of an idiotypic network regulation of the monoclonal B-cell population.

Antibodies, Anti-Idiotypic↗

Characterization of acetylcholine receptor antibodies in a patient with primary biliary cirrhosis.

Antibodies against the acetylcholine receptor were found in a patient with primary biliary cirrhosis. The patient had no clinical or electrophysiological evidence of disturbed neuromuscular function. The antibodies were of both IgG and IgM isotype. Following passive transfer, these antibodies showed the same capacity to bind in vivo to mouse muscle receptors as immunoglobulins from patients with myasthenia gravis. The affinity of the antibodies was high and comparable to that found in myasthenia gravis patients.

Aged↗

Human monoclonal anti-idiotypic antibodies. I. Establishment of immortalized cell lines from a tumor patient treated with mouse monoclonal antibodies.

Patients who undergo immunotherapy with a murine anti-colon carcinoma mAb (mAb17-1A) generate high titers of anti-idiotype and anti-isotype antibodies. Specifically selected anti-idiotypic antibodies that elicit in vivo a humoral and a cellular immune response against the nominal Ag can be used as surrogate Ag for immunization. We established from the B lymphocytes of a treated patient a series of EBV-transformed cell lines. Three weeks after immortalization, the cells were selected for production of antibodies (Ab2) against the Fab fragment of the murine mAb17-1A. The selected cells were cloned and screened by ELISA for specific anti-mAb17-1A idiotypic antibodies. Thirty-six out of 89 clones were anti-idiotypes. Cell culture supernatants and the purified Ig derived from 10 clones completely inhibited the specific binding of radiolabeled mAb17-1A to HT-29 colon carcinoma cells thus resembling Ab2-gamma anti-idiotypes. These cell lines which grow now in culture for 18 mo, continuously secrete IgG,K anti-Ab1-idiotype mAb. Human anti-idiotypic mAb might be candidates for vaccines when the nominal Ag itself is not available or cannot be used as such.

Adenocarcinoma↗

Monoclonal gammopathy and antibody activity against the acetylcholine receptor.

A 50-year-old woman with muscular fatigue and monoclonal gammopathy of unknown significance was shown to have high levels of antibodies against the acetylcholine receptor of the skeletal muscle endplate. The specific antibody activity was exclusively associated with the monoclonal component. There were no objective signs of myasthenia gravis. This is the first reported case with antibody activity against the acetylcholine receptor found in a monoclonal immunoglobulin fraction.

Antibodies, Anti-Idiotypic↗

Anti-acetylcholine receptor antibody related idiotypes in myasthenia gravis.

Anti-acetylcholine receptor antibody associated idiotypes were defined by six murine monoclonal antibodies raised against purified receptor antibodies. Four of the monoclonal antibodies bound to idiotopes located within or close to the antigen binding site of the anti-receptor antibodies; the other two monoclonal antibodies were directed against framework determinants. These monoclonal antibodies recognized idiotopes present on immunoglobulins in 14-60% of patients presenting myasthenia gravis, indicating substantial idiotype sharing. These idiotopes were also found in patients with no detectable anti-receptor antibody activity in their serum. In all patients studied, the pattern of idiotypes fluctuated considerably during the course of the disease regardless of clinical symptoms. This suggests continuous modulation of the autoimmune process in myasthenia gravis.

Animals↗

Clinical effects of monoclonal antibodies (MAb 17-1A) in patients with metastatic colorectal carcinomas.

Ten patients with metastatic colorectal carcinoma were treated with MAb 17-1A (IgG2A). Before infusion, MAb was incubated in vitro with isolated autologous blood mononuclear cells. Treatment was given in repeated courses (2-4 times) to a maximum dose of 1000 mg of MAb 17-1A. One patient achieved a clinical complete remission, two patients had a minor response and one patient had stable disease for 5 months. The median survival for the four responders was 19 months compared to 7 months for the six non-responders. Therapy was well tolerated. In this series, 32 infusions of MAb 17-1A were given. The serum half-life of MAb 17-1A was approximately 22 hours. All patients developed anti-mouse antibodies of both IgG and IgM classes. No relation between adverse reactions and anti-mouse antibodies was seen. At 3 occasions allergic reactions were noted. Skin test with MAb 17-1A seems to reliably predict for allergic reactions.

Adult↗

Renal function and albumin excretion during exercise in children during remission of the minimal change nephrotic syndrome.

Six patients with the minimal change nephrotic syndrome in remission and seven healthy controls were investigated with regard to renal haemodynamics and albumin excretion before, during and after exercise. The glomerular filtration rate and effective renal plasma flow were determined by a standard clearance method, employing continuous infusion of inulin and para-aminohippuric acid. Microalbuminuria was measured by an immunoturbidimetric method. The work load was standardized at 70% of the maximal working capacity and was applied for 20 min. During exercise there was a significant fall in the glomerular filtration rate and effective renal plasma flow and a significant rise in the filtration fraction. The pattern of renal haemodynamic changes did not differ between the groups. Nor was there any statistically significant difference in urinary albumin excretion, although the exercise-induced increase in albumin excretion of the controls did not reach statistical significance. It is concluded that the renal haemodynamics and urinary albumin excretion of children having long remissions of the minimal change nephrotic syndrome are normal at rest as well as during and after a submaximal exercise test.

Adolescent↗

Oligoclonal IgG bands in cerebrospinal fluid. Principles for demonstration and interpretation based on findings in 1114 neurological patients.

Unconcentrated cerebrospinal fluid (CSF) and serum samples from 1114 consecutive patients were examined for presence of oligoclonal IgG bands (OB) by agarose isoelectric focusing (AIF) followed by protein transfer to nitrocellulose membrane, immunolabeling, and avidinbiotin-peroxidase staining (avidin-biotin AIF). Oligoclonal bands were demonstrated in CSF from all 58 patients with multiple sclerosis (MS), eight of 29 with aseptic nervous system infections, and 9% of 1014 with other neurological disorders (OND) considered as noninflammatory at primary clinical evaluation. Comparative examination of all specimens in another laboratory by conventional AIF after concentration of CSF revealed lower frequencies of OB in all diagnostic groups. In addition to the high sensitivity of avidinbiotin AIF, which enables detection of OB by separation of 5 microL of unconcentrated CSF even when the CSF IgG level is around the lower normal range, the procedure also has optimal specificity since IgG exclusively is detected. Avidin-biotin AIF may be the method preferred for routine examination of CSF for OB. Demonstration of OB in CSF is valuable especially in MS, where, in contrast to diagnostic aids such as evoked potentials and neuro-imaging, it establishes inflammatory type of nervous system involvements. Oligoclonal IgG bands in CSF from patients with OND reflect intrathecal immune response and should lead to investigations of infectious etiology.

Adult↗

Human monoclonal immunoglobulins that bind the human acetylcholine receptor.

Myeloma immunoglobulins, once thought to be without any immunological function, are now known to be reactive with many antigens, including self components. We have screened 149 monoclonal immunoglobulin samples and found 14 (9%) to react with the human acetylcholine receptor (AChR). Such anti-AChR antibodies are often associated with the autoimmune disease myasthenia gravis (MG). The anti-AChR binding of the myeloma components was restricted to the F(ab')2 fragment and the affinities were similar to anti-AChR antibodies isolated from MG patients. Despite the presence of anti-AChR antibodies none of the patients exhibited any symptoms of MG.

Antibodies, Monoclonal↗

Residual insulin production, glycaemic control and prevalence of microvascular lesions and polyneuropathy in long-term type 1 (insulin-dependent) diabetes mellitus.

The aim of the present study was to evaluate the role of residual insulin production in long-term Type 1 (insulin-dependent) diabetes mellitus. Ninety-seven patients with a disease duration of 9-16 years and onset before the age of 30 years were studied. C-peptide excretion in 24-h urine samples was measured as an indicator of residual insulin production. Thirty-five patients (36%) excreted C-peptide (greater than or equal to 0.2 nmol); as many as possible of them were carefully matched with a non-excretor patient with regard to age at onset of diabetes and disease duration. Twenty-nine pairs were obtained, and 22 of them agreed to participate in further investigations of glycaemic control and microangiopathic lesions. The patients who excreted C-peptide had significantly lower HbA1c than the non-excretor group, 6.9 +/- 0.3% vs 7.9 +/- 0.3%, (p less than 0.025). Moderate-to-advanced background retinopathy was found in 2 patients in the excretor group and in 7 patients in the non-excretor group. Microalbuminuria [ratio of albumin: creatinine (mg/l:mmol/l) greater than or equal to 5] was found in 1 and in 5 patients, respectively, while proteinuria [ratio of protein: creatinine (mg/l:mmol/l X 10) greater than or equal to 136] was found in 0 and in 4 patients, respectively. Microalbuminuria and/or proteinuria was found in 7 of the non-excretor group as compared to 1 in the excretor group (p = 0.046).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunoactivation in the central nervous system in myasthenia gravis.

To assess signs of immunoactivation within the central nervous system in myasthenia gravis (MG) we examined the cerebrospinal fluid (CSF) of 44 MG patients for certain immunological parameters. Altogether 73% of the patients had some protein and/or cellular abnormality in their CSF. 22 (50%) out of 44 patients had a lymphoid reaction, i.e. a pathologically elevated proportion of enlarged lymphoid cells, in their CSF. In 15 (37.5%) out of 40 patients an enrichment of anti-acetylcholine receptor antibodies in the CSF was observed in relation to serum antibodies. Our findings suggest involvement of the central nervous system in many myasthenia gravis patients.

Adolescent↗