'Rheumatic' hand symptoms as a clue to undiagnosed diabetes mellitus.
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Biomedical subjects
Publications and source records attributed to B Svensson.
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The bactericidal activity of normal monocytes in the presence of serum from 14 patients with SLE was studied with a modification of the Maaloe technique. The bactericidal activity was impaired in the presence of sera from 8/14 patients. The group with abnormal bacterial killing showed higher clinical activity than did the group with normal killing capacity. Corticosteroid therapy was also more common among patients with reduced killing. A further difference between patients with abnormal and normal killing was that the former had more episodes of infection during a 2-year follow-up period.
Monocyte yeast cell phagocytosis was studied in 164 rheumatic sera. The results showed that the phagocytic activity (PA) was low in 51 per cent of SLE-sera, in 12 per cent of other connective tissue disease (CTD)-sera, in 16 percent of RA-sera but in none of 30 sera from patients with other chronic arthritides. Low PA was associated with cryoglobulinaemia and subnormal C1q, C4 and C3 in the SLE-group and with subnormal C4 and signs of extra-articular disease in the RA-group. In the CTD-group, low PA was only found in 4 cases of SLE-like syndromes, all having evidence of vasculitis. The findings suggest that low phagocytic activity in presence of rheumatic sera may be related to clinical syndromes with circulating immune complexes and/or hypocomplementaemia, most often SLE.
A previous article (34) has shown that normal monocytes cultivated in presence of several sera from patients with SLE displayed low yeast cell phagocytosis. In the present extended study it was investigated whether the level of phagocytic activity (PA) had any relation to clinical and laboratory expressions of disease activity. The results reveal that, in addition to hypocomplementaemia and cryoglobulinaemia, low PA was associated with high clinical disease activity including arthritis, rash and nephritis and high titres for anti-nDNA. It was also found that PA improved as the disease activity declined. These findings suggest that this in vitro phagocytosis test might be used as an indirect method for detecting clinically relevant circulating immune complexes in SLE. Furthermore, it might be used as a guide in the evaluation of disease activity in severe SLE. The mechanism behind impaired phagocytosis was not elucidated in this study. Inadequate opsonization of the yeast cells or blocking of the monocyte surface receptors by immune complexes were suggested as possible explanations.
Studies on glass adherence and spreading of normal blood monocytes in presence of sera from patients with systemic lupus erythematosus (SLE) were performed. Spreading was estimated by measuring the cell diameters with a microscale in a phase contrast microscope. Glass adherence (number of glass adherent cells per cultivation chamber) and spreading were found to be significantly reduced in presence of SLE-sera. Furthermore, in presence of these SLE-sera the monocytes formed clusters, which resolved after addition of normal sera. It is suggested that these observations may reflect a disturbance of monocyte membrane function possibly induced by immune complexes or through depletion of complement components in sera from patients with active SLE.
Human mononuclear cells were separated in a Ficoll-Isopaque gradient and incubated in glass chambers in a medium of serum in Parker 199. At the end of the incubation time heat-killed, not pre-opsonized yeast cells (YC) were added for phagocytosis. PA was expressed as the median number of YC per monocyte in 100 monocytes. The results of testing various modifications of this method indicate that an appropriate procedure, allowing a sufficient span for measuring 'subnormal' phagocytosis, is incubation of the monocytes in 15 per cent serum for 120 minutes followed by a further incubation with 10(7) YC (in 7.5% serum) for 30 minutes. The sources of variation in the determination of PA of a standard population was studied by analysis of variance. Based on the results of this study, suitable ways to define and express 'normal' and 'low' phagocytic activity were proposed.
Monocyte yeast cell phagocytosis (YCP) was low in presence of cryoglobulins(CG) from 7 of 7 patients with SLE and RA with vasculitis and from 2 of 5 patients with essential cryoglobulinaemia. IgM and C3 were detected only in CG associated with low YCP. Furthermore, low YCP was only found with CG isolated from hypocomplementaemic sera. The results also showed low YCP when heat-aggregated IgG (HAG) greater than or equal to 19S was added to the culture medium. In the presence of HAG or SLE-sera, preopsonized yeast cells could be adequately phagocytosed by monocytes whereas, in parallel cultures, the phagocytosis of untreated yeast cells was low. It is possible that CG and HAG impair YCP in the same way as SLE-sera. The nature of this presumed common mechanism has not been clarified in this limited study. The findings are, however, compatible with the possibility that immune complexes may interfere with the opsonization of the yeast cells, possibly through inactivation of complement components.
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This study was carried out to evaluate the effects of albumin-bound fatty acids on the anti-platelet effects of endothelial cells. Primary cultures of human endothelial cells (ECM), grown in confluent monolayers, were incubated with plasma or growth medium enriched with albumin-bound fatty acids (FA) for 2-20 h. The effects of ECM on ADP-induced platelet aggregation (PA) and collagen-induced PA and prostaglandin synthesis in platelet-rich plasma were tested. ECM released an inhibitor of platelet reactions which resembled the activity of PGI2 (prostacyclin). The inhibitory activity was increased by preincubation of ECM with arachidonic acid (AA). A moderate decrease of the activity was obtained by incubation with long-chain saturated, monoenoic and dienoic unsaturated fatty acids. A pronounced decrease of the inhibitor was obtained by incubation with di-homo-gamma-linolenic acid (DHLA). Paired combinations of AA with the other fatty acids in the incubation medium partially restored the inhibitory activity obtained by the separate FA. The stimulation of the inhibitor by AA was dose dependent and high concentrations of AA reduced this activity. The present study indicates that the quantity and quality of the plasma free fatty acids can affect the endothelial cells' ability to act as a non-thrombogenic surface.
In order to avoid the potential risk of a short refractory period and the inconvenience of the electronic blocking mechanism at the highest synchronous rate with the conventional atrial triggered pulse generator, two more functions have been added to the normal atrial triggered (VAT) pulse generator. First, it has been designed to be ventricular inhibited; second, a highest synchronous rate detector has been added. When the highest synchronous rate of about 140 is exceeded, the atrial signals are blocked and the frequency of the basic rate generator is increased to about 130. Two patients could hardly feel the change from atrial triggered pacing to ventricular inhibited stimulation, and both were able to work at higher loads with this type of pacing compared with the conventional atrial triggered pulse generator.
Intestinal dipeptidyl peptidase IV and gamma-glutamyltransferase were compared to the corresponding kidney enzymes with respect to immunological and electrophoretic properties. The influences of selected effectors on the two enzymes were also studied. The two kidney peptidases exhibited the reaction of total identity with the corresponding intestinal enzymes in immunodiffusion. Furthermore, the intestinal dipeptidyl peptidase IV and gamma-glutamyl transferase showed the same inhibition patterns as the corresponding kidney enzymes and the acceptor specificity of the intestinal gamma-glutamyl-transferase was found to be identical to that of the kidney enzyme. The electrophoretic mobilities of dipeptidyl peptidase IV from the two organs differed greatly. The difference was almost abolished by treatment with neuraminidase, suggesting that the variation in mobility was due to different contents of sialic acid. It is suggested that the intestinal brush border peptidases, dipeptidyl peptidase IV and gamma-glutamyltransferase, are closely related to the corresponding enzymes obtained from the kidney.
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Human endothelial cell monolayers prepared from umbilical veins have been incubated with aspirin (1--2 mM) dissolved in Hepes modified solution and in platelet-rich plasma. They have also been incubated with plasma prepared from subjects before and after intake of aspirin giving a mean plasma concentration of 0.5 mM. The effects of the endothelial cells on ADP and collagen-induced platelet aggregation and malondialdehyde production in platelet-rich plasma have been tested. The endothelial cells had a spontaneous inhibitory effect on all three parameters. This effect was abolished when the cells were incubated with aspirin dissolved in MHS for 20 min and the increase in effect observed when platelet-rich plasma was incubated with endothelial cells for a period of 30 min was similarly inhibited when aspirin was dissolved in plasma or when plasma prepared from subjects who had taken aspirin were used. Aspirin had no inhibitory effect on prostacyclin (PGI2) with regard to the effect of PGI2 on platelets. On the contrary, the two compounds had an additive inhibitory effect on platelet aggregation induced by ADP and collagen. These findings should be considered with regard to the use of aspirin as an antithrombotic agent.
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Lymphoprep-isolated and glass-adherent mononuclear leucocytes (L-MNs) from the peripheral blood of healthy donors appeared to display directional locomotion towards sparsely distributed yeast cells during continuous observation in coverslip preparations and during observations by means of time-lapse filming in Rose chambers. The phagocytosis-associated L-MN chemotaxis was not inhibited by antitubulin concentrations which were antichemotactic thesis that a direct antitubulin-insensitive chemotaxis exists in L-MNs, besides the antitubulin-inhibited L-MN chemoataxis reported in a previous study.
The inhibitory effects of human endothelial cells (ECM) and PGI2 (prostacyclin) on platelet function have been examined in 60 healthy subjects. 5 groups were studied. I. 10 women (19-33 yrs.); II. 10 women (21-31 yrs.) using combined oral contraceptives; III. 10 postmenopausal women (45-66 yrs.); IV. 20 men (24-48 yrs.) and V. 10 men (48-71 yrs.). Spontaneous platelet aggregation in platelet-rich plasma (PRP) was commonly observed in groups II, III, and V. This was prevented when PRP was incubated with ECM, aspirin (ASA), or PGI2. ADP-induced platelet aggregation (PA) was always reduced by ECM, but significantly less in groups II and III. Collagen-induced PA was inhibited by ECM, but less in groups I, II, III and V than in young men (IV). ECM significantly reduced collagen-induced prostaglandin (MDA) production in platelets. Again, the inhibitory effect was significantly reduced in groups II and III. Platelet factor 3 activity, measured after exposure of PRP to ADP, was significantly reduced by ECM, but was significantly less in groups II, III, and V than in group I. Less of an inhibitory, effect of PGI2 upon ADP-induced PA was shown by all groups of females than by the two groups of males.