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Biomedical subjects

H Permin

Publications and source records attributed to H Permin.

At least 91 records · Page 5Linked to original sources

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↗

Autoantibodies in patients with oral lupus erythematosus, lichen planus and leukoplakia. An aid in diagnosis.

Of 35 patients with oral discoid lupus lesions, 9 (25%) were diagnosed as Systemic (SLE) and 26 as Discoid (dle) lupus erythematosus. Antibodies to whole nuclei (ANAL), dsDNA (anti-DNA ab) and extractable nuclear antigens (anti-RNP ab, anti-Sm ab) as well as serum immunoglobulin levels (Ig) were determined in these patients, in 20 patients with reticular oral lichen planus (LP) and 20 with homogeneous oral leukoplakia (LEUK). High IgG ANA titres were found in the SLE cases, highly increased anti-DNA ab in 6 SLE cases (67%) and one DLE case (4%), slightly increased anti-DNA ab in 9 DLE (35%) but only two (5%) of the LP nd LEUK cases. The prevalence of autoantibodies and increased anti-DNA ab did not differ significantly between DLE cases with oral lesions only and those with cutaneous lesions as well. Increased Ig were present in 6 SLE (67%), 8 DLE (31%), and 3 LEUK (15%) but none of the LP cases. High ANA titres and/or elevated anti-DNA ab disclosed 8 of the 9 SLE and one of 26 DLE cases. Slightly elevated anti-DNA ab and elevated Ig indicated the diagnosis in 9 and 8, respectively, of the 26 DLE cases. It is concluded that determination of ANA, anti-DNA ab and Ig is of diagnostic importance in patients with verified or suspected oral discoid lupus lesions.

Adult↗

Profound sensorineural hearing loss in polyarteritis nodosa. An atypical case of Cogan's syndrome.

Parameters of importance for the development of thrombosis were investigated in a patient with polyarteritis nodosa (PAN) and profound sensorineural hearing loss. During the acute phase, platelet hyperaggregability, shortened platelet survival, and decreased fibrinolytic activity were found. The possibility is discussed that the etiology of the acoustico-vestibular symptoms in this patient could be an inner ear thromboembolic disorder. It is suggested that platelet functions and fibrinolytic activity should be investigated in patients with acoustico-vestibular symptoms and PAN or other systemic diseases. If abnormalities are found, specific platelet inhibitory and/or fibrinolysis-increasing treatment should be considered as an addition to the conventional medical treatment.

Fibrinolysis↗

Platelet 3H-serotonin releasing immune complexes induced by Pseudomonas aeruginosa in cystic fibrosis.

In vitro formation of immune complexes was studied by 3H-serotonin release from human platelets by P. aeruginosa antigens in the presence of serum from 22 cystic fibrosis patients, chronically infected with mucoid P. aeruginosa (CF + P) and with a pronounced antibody response against these bacteria, and in 24 patients without P. aeruginosa (CF-P). All CF + P patients responded with 3H-serotonin release (16-34%), whereas CF - P patients released less than 15%. In group of CF + P patients the number of P. aeruginosa precipitins was correlated to the serotonin titer. Time courses indicated that 3H-serotonin release was maximal between 2 and 5 min, and that no further release was observed up to 20 min. There was a gradual increase in 3H-serotonin release with higher platelet concentrations. The response was not changed by complement inactivation, and fractionation of serum demonstrated that the serotonin release was dependent on the presence of the immunoglobulin fraction. These experiments support the suggestion of a type III reaction being involved in the lung damage in CF + P patients and also suggest a possible involvement of serotonin in he inflammatory reaction during chronic P. aeruginosa lung infection.

Adolescent↗

Basophil histamine release and humoral changes during immunotherapy. Dissociation between basophil-bound specific IgE, serum value, and cell sensitivity.

An in vitro pilot study was performed to determine whether basophil cell-bound specific IgE was correlated to serum-specific IgE and to basophil cell sensitivity during immunotherapy with a well-documented treatment. The findings showed a clear dissociation between these three parameters, which is in contrast to the situation before hyposensitization and to our previous study in a comparable group of non-hyposensitized patients, where highly significant correlations were observed. Further investigations are in progress to clarify whether the dissociation is involved in the clinical improvement.

Allergens↗

IgE anti-IgG antibodies in patients with juvenile and adult rheumatoid arthritis including Felty's syndrome.

Anti-IgG antibodies (anti-IgG) of the IgE class were studied in sera from patients with juvenile rheumatoid arthritis (JRA), rheumatoid arthritis (RA) and patients with Felty's syndrome (FS) by use of an indirect immunofluorescence technique. Forty-two per cent of 26 patients with JRA had IgE anti-IgG in serum all in low titers. Positive reactions prevailed in patients with multiple joint involvement. Sixty-three per cent of 30 patients with RA and 80% of 20 patients with FS had IgE anti-IgG, the titers found in FS patients being significantly higher. In JRA and FS patients the IgE anti-IgG titers were correlated to the titers of anti-IgG of the IgG class, and for FS patients also with the IgM and IgA classes of anti-IgG. In six of 10 patients with RA the synovial fluid samples from both knees contained IgE anti-IgG. In four of these patients the titers of IgE anti-IgG were higher than in the corresponding serum sample, pointing to a local production. After G-200 Sephadex chromatography IgE anti-IgG were demonstrated in the void volume indicating the presence of these autoantibodies in immune complexes. IgE anti-IgG may be involved in the pathogenesis of JRA and RA by eliciting Type I and III reactions.

Adolescent↗

The significance of antinuclear antibodies in juvenile rheumatoid arthritis associated with chronic bilateral iridocyclitis.

Serum samples from 8 children with juvenile rheumatoid arthritis (JRA) and chronic bilateral iridocyclitis were significantly distinguished from 5 children with JRA and no eye symptoms by the presence of large immune complexes (IC) greater than 22S, IgM antinuclear antibodies (ANA), IgG granulocyte-specific (GS-) ANA, C3 fixing ANA, and IgM anti-IgG. One serum with and two sera without IC greater than 22S, all from patients with iridocyclitis, were fractionated by rate zonal ultracentrifugation. Each fraction relevant for the study was separately concentrated and reexamined. In one of the sera without IC greater than 22S this technique exposed the presence of IgA GS-ANA not detectable in the corresponding whole serum. IgG ANA were precipitated in an area with higher molecular weight than the one for IgG indicating the presence of aggregated IgG ANA. Fractionation of the serum with IC greater than 22S demonstrated IgM GS-ANA not present in whole serum. The results support previous suggestions that ANA may be involved in the pathogenesis of chronic iridocyclitis and may explain why ANA (in particular C3 fixing ANA) negative patients with JRA rarely develop chronic iridocyclitis.

Adolescent↗

Hepatitis B virus infection in patients with rheumatic diseases.

Two hundred and thirty-nine patients with different rheumatic diseases were investigated for serological markers of hepatitis B virus (HBV) infection. An increased prevalence of anti-HBs was found in patients with systemic lupus erythematosus. The total prevalence of HBV markers in patients with polymyalgia rheumatica, temporal arteritis, juvenile and adult rheumatoid arthritis (RA) and systemic sclerosis was not significantly different from age-matched controls. Remarkably, 6 patients were HBsAg-positive of whom 3 had RA (4%). Two patients with RA were "healthy' HBsAg carriers. The third patient had circulating HBeAg as well and had shown progression from acute hepatitis to cirrhosis during the time of observation. Three of 18 patients with polyarteritis nodosa were HBsAg- and HBeAg-positive, and all 3 were young men. Clinical improvement was seen in one of these patients and was associated with seroconversion from HBeAg to anti-HBe. Our data do not support the theory that HBV is an aetiological factor in rheumatic diseases except in some cases of polyarteritis nodosa.

Adolescent↗

Characterisation of Liver membrane autoantibodies determined by indirect immunofluorescence.

Indirect immunofluorescence studies were performed using sera and IgG-Fab2 fragments from patients with chronic active hepatitis (CAH) who were positive for a liver membrane antibody (LMA). The specificity was investigated using hepatocytes from humans as well as rabbit, rat, guinea pig and monkey. Only sera also positive for smooth muscle antibody gave staining of lymphocytes and absorption with F-actin from rabbit muscle abolished this as well as all other smooth muscle staining without influencing LMA. It was concluded that LMA, routinely detected by indirect immunofluorescence using rabbit hepatocytes, represents specific binding to non-species-specific membrane antigens which are normal constituents of human hepatocytes. The antigen is separately located, and not cross-reactive with F-actin.

Animals↗

Circulating immune complexes involving autoantibodies in chronic active hepatitis.

The mere presence of circulating immune complexes has been extensively reported in inflammatory liver diseases. In the present study, immune complexes were determined in 6 patients with HBsAg-negative chronic active hepatitis by sucrose density gradient ultracentrifugation. If present they were characterized concerning size and possible autoantibody-specificity. In four of these patients, zonal profiles differed markedly from normal controls and high molecular weight IgG-reactive substances with specificity against nuclear, smooth muscle and liver membrane antigens were demonstrated. Two patients were investigated repeatedly during one year of prednisone therapy and complex levels and size decreased along with clinical and biochemical improvement. Also in four positive controls with active SLE, complexes of up to 38 S containing antinuclear antibodies were detected. In contrast to patients with chronic hepatitis, SLE patients all had normal levels of serum gammaglobulin. It was concluded that immune complexes, present in liver disease without systemic organ-involvement and containing autoantibodies, might possibly reflect the normal immune clearance.

Adolescent↗