Search PubMed⌕ Search

Biomedical subjects

G Sturfelt

Publications and source records attributed to G Sturfelt.

138 records · Page 8Linked to original sources
PubMed1980

Complement activation, circulating C1q binding substances and inflammatory activity in rheumatoid arthritis: relations and changes on suppression of inflammation.

Patients with rheumatoid arthritis were treated with podophyllotoxin derivatives (PTD) or with cyclophosphamide. Increased concentrations of C1r-C1s-C1 inactivator complexes (C1r-C1s-C1 IA) in serum provided evidence for C1 activation, which was most pronounced before treatment. During treatment the levels of C1r-C1s-C1 IA clearly decreased, while the levels of C4 increased. This rise in C4 was contrasted to the decrease in other acute phase reactants as C-reactive protein. Circulating immune complexes were assessed by the C1q deviation test (C1q DV) and the C1 binding assay (C1q BA). Discrepancies were noted in the outcome of the two assays. Of parameters reflecting C1 inactivation C1r-C1s-C1 IA complexes were positively and C4 negatively correlated with the inflammatory activity as measured by synovitis index (SI). The values in C1q DV correlated with the C1r-C1s-C1 IA values and with SI. In contrast, C1q BA correlated with CRP but not with C1r-C1s-C1 IA or SI. The study gave evidence for a relationship between C1 activation as detected in serum and the extent of synovial inflammation in RA. The possibility is discussed that substances other than immune complexes may be involved in C1 activation and contribute to the synovial inflammation.

Adult↗
PubMedDate not supplied

Kinetic analysis of immune complex solubilization: complement function in relation to disease activity in SLE.

Solubilization of preformed bovine serum albumin (BSA) rabbit anti-BSA complexes in serum with kinetic analysis, haemolytic complement function, complement proteins C1q, C4, C3 and complexes containing C1 inhibitor (C1 INH-C1r-C1s-C1 INH) were serially investigated in relation to disease activity in 25 patients with systemic lupus erythematosus (SLE). Clinical assessment of disease activity was expressed using a validated global index (SLEDAI). Markedly decreased capacity to solubilize immune complexes in serum was mainly found in sever disease. By serial analysis, evidence of fairly persistently impaired classical pathway function was found in most of the patients. In partial contrast, impaired alternative pathway function was more clearly associated with active severe disease. Immune complex solubilization during short incubation (5-10 minutes) correlated with classical and alternative pathway-mediated haemolysis. Solubilization during long incubation (40 minutes) was correlated with haemolytic alternative pathway function. In some patients gradual impairment of solubilization during short incubation, and reduced classical pathway haemolytic activity were detectable 2-4 months before clinical manifestations prompted therapeutical intervention. SLEDAI was negatively correlated with solubilization during prolonged incubation (40 minutes) and with haemolytic alternative pathway function, further emphasizing involvement of the alternative pathway in severe disease. The findings emphasize the importance of impaired complement function due to complement activation in SLE. Assays for immune complex solubilization or other complement functions appear to be useful for monitoring disease activity in SLE.

Antigen-Antibody Complex↗
PubMedDate not supplied

Random locomotion and phagocytosis of monocytes in undiluted normal serum and in undiluted SLE serum.

Time-lapse filming was performed with normal monocytes in normal serum and in SLE serum, with and without yeast cell phagocytosis. Undiluted sera were used. After incubation of the monocytes with SLE serum we found a decreased velocity of random movement and a change of morphology to more condensed, rounded-up and un-spread cells with a decreased yeast cell phagocytosis. No obvious correlation was found between the SLE serum induced impairment of monocyte function and disease activity, complement levels or the presence of immune complexes. We conclude that monocyte in vitro membrane functions, such as random motility, spreading and yeast cell phagocytosis, are impaired in the presence of undiluted SLE serum.

Adult↗
PubMedDate not supplied

Inhibition of ConA-induced proliferative response in human lymphocytes by podophyllotoxin and a detergent, Tween80.

Podophyllotoxin (CPH86), at concentrations of 5 ng/ml or more, inhibited [3H]-thymidine uptake of ConA-induced proliferation of human peripheral mononuclear blood cells. Tween80, the detergent included in the anti-inflammatory drug Proresid, containing podophyllum lignan derivatives, also inhibited lymphocyte proliferation in a dose-dependent manner. Combination of the two drugs did not, or did only weakly, potentiate the inhibitory effect of each drug.

Concanavalin A↗
PubMedDate not supplied

Clinical inconsistency, benign course and normal employment rates in unselected systemic lupus erythematosus.

Of 65 unselected SLE patients from a defined population, 61 were sequentially followed for two years with an SLE supervision programme. The cumulative clinical manifestations included a relatively high frequency of pulmonary vascular disease and gastrointestinal involvement. Flares were more common during the summer season and a change in the clinical manifestations occurred in 10 of 16 patients with major flares and in 4 of 13 patients with minor flares. ESR, S-orosomucoid, S-CRP, and C1r-C1s-C1 IA complexes, indicating C1 activation, were shown to distinguish inactive from active disease. The prevailing overall benignancy was reflected in a low mortality rate, limited need for treatment or hospitalisation, and good response to moderate dosages of corticosteroids in severe flares. The proportion of patients in gainful employment was comparable to that in the normal population, though absence due to sickness was more common in the SLE group. Joint complaints and mild psychiatric disturbance were the most common causes of enduring incapacity.

Adult↗
PubMedDate not supplied

Complement activating rheumatoid factors in rheumatoid arthritis studied by haemolysis in gel: relation to antibody class and response to treatment with podophyllotoxin derivatives.

Complement (C) activating rheumatoid factors (RF) were measured in 16 patients with rheumatoid arthritis (RA) by a simple haemolysis in gel (HIG) assay. IgM-RF, but not IgG-RF or IgA-RF, measured by an enzyme linked immuno-sorbent assay, were closely correlated with C activating RF (r = 0.86). In neither assay did the concentrations of RF appear to be directly related to C1 activation as expressed by serum concentrations of C1r-C1s-C1 inactivator complexes or of C4. In the sera, C1q binding substances, measured by C1q binding assay, were markedly correlated with C activating RF (r = 0.88), whereas C1q binding substances detected by the C1q deviation test were not. Treatment with podophyllotoxin derivatives for 6 months clearly reduced patients' RF concentrations. The decrease of IgG-RF, IgA-RF and IgM-RF was significantly more pronounced than that of the IgG, IgA and IgM concentrations, respectively.

Adult↗
PubMedDate not supplied

False-positive Waaler-Rose test due to anti-rabbit IgM antibodies in IgA deficiency.

The presence of antibodies to rabbit IgM in an IgA deficient patient with degenerative arthropathy is described. The anti-IgM antibodies caused a false-positive Waaler-Rose test. Antibodies to rabbit IgM in titres greater than or equal to 1/8 were found in 20 of 35 IgA deficient individuals. No relationship between the patients' symptoms and the presence of these antibodies could be discerned and their biological significance is unknown. Two of 100 normal blood donors, none of 62 rheumatoid arthritis patients and 9 of 50 systemic lupus erythematosus patients showed anti-rabbit IgM antibodies in titres greater than or equal to 1/8. Unless an IgG fraction of antibodies is used for sensitization of erythrocytes in the Waaler-Rose test, the results may be misleading.

Agglutination Tests↗
PubMedDate not supplied

Antiproliferative effects on human peripheral blood mononuclear cells and inhibition of in vitro immunoglobulin synthesis by Podophyllotoxin (CPH86) and by semisynthetic lignan glycosides (CPH82).

A mixture of natural and semisynthetic (modified) glycosides from Podophyllum emodi (Proresid) has been used for many years in the treatment of rheumatoid arthritis, but its use is hampered by gastrointestinal side effects. Highly purified podophyllotoxin (CPH86) and a preparation containing two semisynthetic podophyllotoxin glycosides (CPH82) are currently being tested in clinical trials. In this study these drugs were shown to inhibit in vitro [3H]-thymidine uptake of human peripheral blood mononuclear cells stimulated by the mitogens concanavalin A, phytohemagglutinin and pokeweed mitogen. Complete inhibition was observed with CPH86 in concentrations > or = 20 ng/ml and with CPH82 in concentrations > or = 1 microgram/ml. In vitro production of IgG, IgM and IgA by PWM-stimulated cells cultured for 7 days was unaffected by 10 ng/ml CPH86 and 100 ng/ml CPH82, but was strongly inhibited by concentrations of CPH86 at > or = 20 ng/ml and CPH82 at > or = 1 microgram/ml. In conclusion, both CPH86 and CPH82 inhibit mitogen induced lymphocyte proliferation and immunoglobulin synthesis and the results may be of help in determining optimal dose levels if related to treatment effects.

Cell Division↗
PubMedDate not supplied

Prospective analysis of C1 dissociation and complement activation in patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate the results of complement analysis for assessment of disease activity and severity, and prediction of flares in systemic lupus erythematosus (SLE). METHODS: Patients with mild extra-renal flares, severe extra-renal flares or flares of lupus glomerulonephritis were followed for eight months, with investigations being performed every second month. Findings in initial samples four months before the flares were compared with findings in a control group with stable disease. C-reactive protein, and circulating C1q, C4 and C3 were determined together with two types of complexes containing C1 inhibitor (C1 INH), C1 INH-C1r-C1s and C1 INH-C1r-C1s-C1 INH, and the C3 breakdown product C3d. RESULTS: Enhanced formation of C1 INH-C1r-C1s appeared to be a marker of low specificity and was mainly seen in patients with extra-renal disease. Concentrations of C1 INH-C1r-C1s-C1 INH, C3d, C1q and C3 clearly varied according to disease activity in patients with severe disease. Interestingly, high C1 INH-C1r-C1s-C1 INH values were found four months before the flares in all but one patient with lupus glomerulonephritis. Assessment of the relative predictivity for a subsequent flare indicated low C1q to be the most reliable marker, the predictivity of the complexes being: low C1q > high C1 INH-C1r-C1s-C1 INH > low C3 > high C3d > low C4. CONCLUSION: The importance of C1q and C1-related events in SLE may be underestimated. In addition, our results demonstrate the relevance of serial complement analysis for the assessment of disease activity and severity.

Adolescent↗