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Biomedical subjects

H Permin

Publications and source records attributed to H Permin.

At least 73 records · Page 4Linked to original sources

Immunoglobulins, anti-IgG antibodies and antinuclear antibodies in paired serum and synovial fluid samples. A comparison between juvenile and adult rheumatoid arthritis.

Paired samples of serum and synovial fluid (SF) from 13 patients with juvenile rheumatoid arthritis (JRA) and 10 patients with adult rheumatoid arthritis (RA) were examined regarding the level of immunoglobulins and the occurrence and titres of anti-IgG antibodies and antinuclear antibodies (ANA). The levels of immunoglobulins were lower in SF than in serum. In JRA the SF/serum ratio of IgG was equal to that of albumin, pointing to a local production of IgG. The SF/serum ratio of IgM was equal to that of alpha 2-macroglobulin. In JRA the SF/serum ratios of immunoglobulins tended to be lower than in RA, the difference being significant for IgM. IgD autoantibodies and IgA anti-IgG were not found in JRA. IgE autoantibodies occurred in some cases, but in RA in more than 60%. In JRA the SF titres of anti-IgG and ANA were most often lower than the serum titres. In RA the SF titres were often higher than the serum titres. In 9 of 10 paired SF samples from patients with RA the SF/serum ratios were mutually different with regard to one or several immunoglobulins. Evidence of synovial production of anti-IgG antibodies of classes other than IgG distinguished RA from JRA. Otherwise the differences were quantitative.

Adolescent

Lectin-mediated reactions in histamine release caused by bacteria.

The bacteria-induced release of histamine was studied in human basophil leukocytes and in isolated rat mast cells. Whole bacteria of Staph. aureus caused release in a 98% pure population of peritoneal mast cells from germ-free rats, indicating a non-immunological mechanism and a direct interaction between the bacteria and the target cells. Probably the bacterial cell wall interacts with the cell membrane, since a preparation of the bacterial cell wall caused a dose-dependent release of histamine from basophil leukocytes similar to that induced by whole bacteria, and repeated washing of whole bacteria did not change the release. Inhibition studies by lectin-binding sugars indicate that aminosugars on the bacterial surface of Staph. aureus interact with lectins on the basophil cell membrane leading to histamine release.

Adult

Basal cyclic AMP levels in human blood mononuclear cells.

Basal cyclic AMP levels in blood mononuclear cells from healthy human donors has been studied. A great variation in cyclic AMP content ranging from below 2 to 20 pmol 10(-6) cells was seen. Incubation of the cells at 37 degrees C mostly showed a time-dependent decrease in basal cyclic AMP, levelling off after 16 h. When treated synchronously, cells from blood from the first sample of blood sampling contained more cyclic AMP than that of later samples. Presence of adenosine deaminase, theophylline or indomethacin influenced cyclic AMP concentrations in a non-consistent manner. Variations in cyclic AMP content may in some individuals be ascribed to early increase of cyclic AMP, in others to a progressive reduction in basal cyclic AMP during blood sampling, cell preparation and incubation.

Adenosine

Type I allergy to normal cellular constituents in chronic inflammatory bowel disease? Results from basophil histamine release test compared with total IgE and antinuclear antibodies.

The possibility of autoimmune type I reactions to cellular constituents was investigated in 22 patients with ulcerative colitis, 12 with Crohn's disease, and in 22 healthy volunteers. Nuclear components and colon mucosa fragments were tested as potential antigens by the basophil histamine release technique. One of 12 patients with ulcerative colitis responded to sonicated leukocyte nuclei and one of 12 patients with Crohn's disease responded to both nuclei and RNA. Increased serum levels of total IgE and antinuclear antibodies of IgE class were found in one and three of the 24 patients, respectively. Histamine release caused by colon mucosa fragments was not observed in a separate study consisting of 10 ulcerative colitis patients and 10 healthy volunteers. Autoimmune type I allergy to cellular constituents does not seem to be of significance for chronic inflammatory bowel disease and thus could not explain the involvement of tissue mast cells and eosinophils in this condition.

Adult

Antibodies against nuclear components in schistosomiasis. Results compared to values in patients with rheumatoid arthritis, systemic lupus erythematosus, and osteoarthrosis.

Occurrence of autoantibodies against nuclear material was compared in groups of patients with rheumatoid arthritis (RA n = 22), systemic lupus erythematosus (SLE n = 24), osteoarthrosis (OA n = 25), and chronic schistosomiasis mansoni (CSM n = 28). Anti-ds DNA antibody was detected by an ammonium sulphate precipitation radioimmunoassay antibodies against extractable nuclear antigen (ENA) were detected and differentiated in RNAse-resistant and RNAse-sensitive components (Sm and RNP antigens) with an ELISA technique. IgG organ-non-specific and granulocyte-specific antinuclear antibodies (ANA) were detected by immunofluorescence technique with quantitative titration of positive reactions and determination of complement-fixing properties. The results in groups of patients with SLE, RA and OA were of confirmative nature and supported that the different methods detect different systems of autoantibodies and nuclear autoantigens. In CSM it was demonstrated that 23 of 28 cases had positive reactions to the RNAse-resistant part of ENA (the Sm-antigen), a significant difference from the three other groups of patients (P less than 0.001). The antibody was in all cases of IgM class, in seven cases also of IgA class. Antibodies against nuclear material in CSM are probably a consequence of heavy disturbance of the immune system in this chronic infection with great permanent antigen load. It is a matter of discussion, whether production of these antibodies is induced by nuclear material from the host or from the parasite.

Adolescent

Bacterial histamine release by immunological and non-immunological lectin-mediated reactions.

The mechanisms of bacteria-induced histamine release were examined in vitro in human leukocytes and rat mast cells. Three types of bacterial responders were found. In persons with IgE-bearing basophilocytes bacterial histamine release could be triggered by two different mechanisms, an IgE-dependent mechanism where removal of IgE abolished the release and a non-immunological mechanism where this was not the case. In responders with no IgE-bearing cells bacterial histamine release was caused by a non-immunological mechanism. The non-immunological mechanism was further substantiated by release in isolated mast cells from germ-free rats. These experiments suggest a direct interaction between bacteria and target cell, and experiments with multi-washed bacteria and bacteria cell wall preparations indicate the possibility of the bacteria wall interacting with the target cell. It is probable that the non-immunological mechanism depends on lectin-mediated reactions, since bacteria-induced histamine release was inhibited by lectin-binding sugars as is release caused by plant lectins.

Basophils

Determination of IgE-containing immune complexes in human sera. Evaluation of polyethylene glycol precipitation of monomeric and complex IgE and of the detectability of IgE in the complexes.

We studied the polyethylene (PEG) precipitability of monomeric human IgE, and of human IgE artificially complexed with rabbit anti-human IgE. At conditions where precipitation of monomeric IgE did not occur, from 0.2 to 20% of the complexed IgE was precipitated. The PEG precipitability of the complexes was inversely related to the IgE/anti-IgE ratio used for preparation of the complexes. From 1.5 to 19.2% of the IgE in the redissolved precipitates could be detected by use of a two-site IgE immunoradiometric assay, the percentage being highest for complexes formed at equivalence. We conclude that exact quantitation of circulating IgE immune complexes (IC) probably is impossible by any PEG precipitation assay. However, the optimized assay was found to be useful for identification of IgE IC in sera with total IgE concentrations below 5,000 U/ml. IgE IC were found in 5/20 sera from patients with Felty's syndrome, in 5/39 sera from patients with extrinsic allergy and high levels of specific IgE, and in 1/17 sera from immunized wasp allergics. No IgE IC were found in 20 normal human sera.

Antigen-Antibody Complex

Phagocytosis by normal polymorphonuclear leukocytes of immune complexes from serum of patients with Felty's syndrome and rheumatoid arthritis with special reference to IgE immune complexes.

Sera from patients with Felty's syndrome, rheumatoid arthritis (RA) and controls were investigated for the presence of immune complexes (IC) using phagocytosis by normal polymorphonuclear leukocytes and direct immunofluorescence technique. IC visible as large cytoplasmic inclusions were seen in 19 of 24 cases of Felty's syndrome, 3 of 16 cases of RA, and all 3 patients with extraarticular manifestations, and none of 21 control sera. IC containing IgG, IgA and complement C3 were found in nearly all positive cases. IgM IC were found in only 8 of the Felty's syndrome cases, IgE in 5 and beta-2-microglobulin in one case, respectively. A tendency to increasing number of large inclusion positive cells in vitro was found inversely correlated to the number of circulating leukocytes in the Felty patients at the time of serum sampling. In contrast, small cytoplasmic inclusions were found both in Felty's syndrome and RA patients and in some of the controls, and IgG and C3 were the most frequent constituents in these cases. As these inclusions were found in all groups it may have little significance. IgE IC as determined by a PEG precipitation technique were positive in the same 5 cases of Felty's syndrome with IgE containing inclusions, and in one case of RA with extraarticular manifestations. The complexed IgE amounted to about 3% of the total serum concentration of IgE. Phagocytosed IC may be involved in the pathogenesis of neutropenia and contribute to the inflammatory processes in Felty's syndrome.

Adult

IgE class immune complexes in Felty's syndrome: characterisation of antibody activities in isolated complexes.

By means of a double polyethylene glycol (PEG) precipitation and PRIST technique IgE was detected in 3% PEG precipitates and in the immune complex enriched fractions purified by solid-phase Clq adsorption from sera of 11 of 20 patients with Felty's syndrome. No correlation was found between the occurrence of complexed IgE and total protein content of the immune complex enriched material. IgE rheumatoid factor and anti-IgE antibody activity were detected in some of the immune complex fractions. Serum levels of complement C3, C4, and factor B were low in IgE immune complex positive cases. Only 4 of 20 patients with articular rheumatoid arthritis had IgE-containing immune complexes.

Aged

Autoimmune type I reactions directed against nuclear components in rheumatoid arthritis.

Basophil histamine release was examined in leucocyte suspensions from patients with rheumatoid arthritis (RA) after challenge of the cells with isolated and sonicated leucocyte nuclei from normal individuals. Most of the patients with active disease responded with significant histamine release, whereas no response was obtained in the inactive patients and in normal controls. A similar pattern was found in the urinary excretion of the main metabolite of histamine, NT-methyl-imidazoleacetic acid, since an increased excretion was observed in most patients with severe disease activity in contrast to patients with moderate and quiescent activity and the control group. These findings strongly indicate an involvement of autoimmune allergic type I reactions in RA. The release of histamine and other mediators from basophils and mast cells may cooperate in the inflammatory reactions and the destruction of the joints in RA.

Adult

High serum beta-2-microglobulin levels and circulating immune complexes containing beta 2m and anti-beta 2m antibodies in Felty's syndrome.

Serum beta-2-microglobulin (beta 2m) levels, incidence and levels of anti-beta 2m autoantibodies, and quantity of circulating macromolecular complexes containing beta 2m were studied in patients with Felty's syndrome (FS), joint-restricted rheumatoid arthritis (RA), and healthy controls. The serum beta 2m concentrations detected in the FS group (6.95 +/- 2.9 mg/liter) greatly exceeded those of the RA group (3.4 +/- 1.2 mg/liter) and the control group (1.42 +/- 0.69 mg/liter). Autoantibodies to beta 2m were frequent in the FS group. Circulating complexes containing beta 2m, prepared by precipitation in 3% polyethylene glycol, were detected in 65% of FS and 35% of RA patients. In the majority of these cases the solid-phase C1q purified immune complexes also contained beta 2m. Detection of anti-beta 2m antibodies in a significant part of complexes containing beta 2m suggests the presence of specific immune complexes in this fraction of FS and RA patients.

Antibodies

Intrinsic asthma and bacterial histamine release via lectin effect.

Bacteria-induced histamine release from basophil leukocytes was observed in vitro in both children with intrinsic asthma (IA) as well as in normal individuals. In vivo the release is suggested to take place only in the lung of IA patients, where a defective pulmonary barrier would permit the bacteria to enter, but not in healthy individuals. The study indicates that two different mechanisms of bacterial histamine release might exist, an IgE-mediated reaction and a non-immunological mechanism consisting of a direct interaction with the basophil cell surface. The non-allergic mechanism might depend on a lectin effect where bacterial surface lectins interact with the basophil cell surface leading to release of histamine. Inhibition studies with carbohydrates suggest a multi-lectin reaction in the bacterial histamine release involving several types of lectins on the bacterial membrane reacting with different carbohydrate moieties on the cell surface of basophil leukocytes.

Asthma

Ceftazidime treatment of chronic Pseudomonas aeruginosa respiratory tract infection in cystic fibrosis.

Two open randomized cross-over studies were undertaken comparing ceftazidime to tobramycin and ceftazidime to tobramycin plus carbenicillin in 13 and 15 cystic fibrosis (CF) patients, respectively, with chronic bronchopulmonary Pseudomonas aeruginosa infection. The difference in lung function improvement was statistically better in terms of FEV1 and FVC for the ceftazidime group in the study versus tobramycin plus carbenicillin. Patients receiving ceftazidime showed a tendency for a greater long-term benefit in lung function as measured at 1 and 2 months after treatment than patients receiving the other antibiotics. Development of resistance against both ceftazidime and carbenicillin was seen regularly and was not prevented by combination therapy with tobramycin. No resistance developed when tobramycin was used as monotherapy. Serum concentration curves for ceftazidime fitted a two compartment first order open model in CF patients and showed a distribution volume of 40% of the body weight and a final serum half-life of 1.8 h. One case of Type III hypersensitivity reaction was seen during ceftazidime treatment. Ceftazidime seems to be an effective and safe antibiotic in the treatment of Ps. aeruginosa bronchopulmonary infection in CF patients, although these bacteria could not be eradicated.

Adolescent

Basophil histamine release induced by leukocyte nuclei in patients with rheumatoid arthritis.

Leukocyte suspensions containing basophils were obtained from 23 patients with rheumatoid arthritis (RA). When these cells were incubated with leukocyte nuclei from normal persons, histamine release was seen in 11 of the 15 patients with active disease, but not in the quiescent group or in normal individuals. The dose-response curve for histamine release was similar to that obtained by specific antigen in type I allergy. By removal from and refixation to the cells of surface Ig, the release of histamine was respectively, abolished and restored, just as in similar experiments in hay fever patients. The dependence of pH for removal was also identical with that found in type I allergy. Antinuclear antibodies of the IgE class (IgE ANA) mainly directed against the granulocyte nuclei were often found in serum and on the cell surface of the RA patients, but not in normal individuals. A correlation was found between these titres in serum and on the cell surface. No correlation was found between ANA in serum and on the cell surface, on the one hand and disease activity and histamine release on the other. In a group of 12 patients with another joint disease, osteoarthrosis, only two patients showed histamine release, and in contrast to the other patients they showed swelling of more than two joints. The present investigation supports our hypothesis of an involvement of an autoimmune type I reaction directed against nuclear components in the RA disease.

Adult

Amyloid-related serum protein (SAA) as an indicator of lung infection in cystic fibrosis.

Amyloid-related serum protein (SAA) was analysed by radioimmunoassay in 32 patients with cystic fibrosis, and compared with other acute phase reactants and lung function. The level of SAA showed significant correlation with impaired lung function due to active Pseudomonas aeruginosa infection, and also to C-reactive protein. SAA seemed to correlate better to the presence of bacteria in sputum than C-reactive protein. Ten of the patients received extensive antibiotic treatment for their pulmonary infection, and falling serum levels of SAA paralleled the clinical response to treatment. Thus the concentration of SAA in these patients was a valuable guide for the selection of patients for antibiotic treatment as well as a good parameter of the response to therapy.

Adolescent

Treatment of chronic pseudomonas aeruginosa infection in cystic fibrosis patients with ceftazidime and tobramycin.

50% inhibitory concentration (IC50) and minimum inhibitory concentration (MIC) of ceftazidime, cefsulodin, cefotaxime, moxalactam, azlocillin, carbenicillin, netilmicin and tobramycin against 90 strains of Pseudomonas aeruginosa isolated from cystic fibrosis (CF) patients were determined by means of the agar plate dilution method. Ceftazidime was most active of the antibiotics in vitro; the geometric mean of IC50 was 0.2 and of MIC 0.4 micrograms/ml. 11 CF patients suffering from P. aeruginosa infection were treated with 14 day courses of ceftazidime (100 mg/kg/24 h) and tobramycin (10 mg/kg/24 h). P. aeruginosa was only temporarily eradicated in one of the patients, but a significant improvement of respiratory function and a significant fall in white blood cell count was recorded in the patients during chemotherapy. There was no development of resistant strains against ceftazidime during treatment and no side-effects were observed. Ceftazidime is a promising new antimicrobial agent with high in vitro activity which deserves further in vivo evaluation in CF patients.

Adolescent