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[Clinical evaluation of immuno-serological laboratory data].

Clinical evaluations of various laboratory data from immuno-serological tests such as rheumatoid factor, anti-nuclear antibody, and other auto antibodies were reviewed. Rheumatoid factors (RF) were discussed in relation to positivity in various diseases, immunoglobulin class of RF, and correlation between titers of RF and circulating immune complex (IC). As a result, higher frequency and higher titers of IgA-RF were found in Sjögren syndrome patients. Titers of RF did not show disease activity of RA, but those of ESR and CRP did. Anti-nuclear antibodies (ANA) were discussed in relation to positivity in healthy subjects, specific antibodies and corresponding specific disease, correlation among titers of anti-dsDNA antibody, CH50 and circulating immune complex. As a result, an ANA frequency of 40% was found in healthy young women. Values of CH50 were much better than ANA titers for evaluating clinical activity in SLE patients. Findings of anti-cardiolipin antibody in thrombosis patients with connective tissue vascular disease (CVD), anti-centromere antibody in various CVD patients as well as CREST patients and primary biliary cirrhosis patients and anti-neutrophil cytoplasmic antibodies in various vascular diseases along with inflammatory bowel disease patients were presented. Finally, useful laboratory data at different clinical steps such as diagnosis, evaluation of disease activity and estimation of prognosis were demonstrated in CVD.

Adult↗

Blood interaction with a Bioline heparin coated HIA-VAD: a study on calves.

The blood compatibility of ventricular assist devices developed by the Helmholtz Institute Aachen (HA-VAD's) was tested on calves. Seven calves received a non-coated HIA-VAD (control) and three a Bioline heparin coated device. The circulatory support of these HIA-VAD's lasted one week. Mechanical blood cell trauma estimated by hematocrit (Hct), hemoglobin (total Hb) and free plasma hemoglobin (free Hb) levels did not differ in either group. All HIA-VAD's in the control group remained thrombus free, except on one occasion when an inflow cannula was obstructed by a thrombus located in the tip. After circulatory support, the animals in this group seemed clinically healthy. However, thrombus formation was observed in the three heparin coated HIA-VAD's. One animal in this group died from complications after re-operation for pneumothorax on the fifth day of support, whereas the other two animals seemed clinically healthy. In these three animals, a strong decrease in platelet numbers was measured even after 24 hours of support which recovered after 72 hours. This decrease in platelet numbers was associated with a lower degree of platelet aggregation ability stimulated by ADP (p < 0.05). Fibrin(ogen) degradation products (FDP) increased significantly immediately after the implantation procedure (p < 0.05). Fibrinogen levels initially decreased during the implantation procedure, but increased thereafter in both groups. The FDP levels remained high in this group, although the FDP levels in both groups were decreased after the implantation procedure. The ex vivo measured circulating heparin levels were lower in the heparin coated HIV-VAD group despite the equally administrated heparin doses in both animal groups. No differences were measured in either group with regard to white blood cell (WBC) numbers and complement hemolytic activity (CH50). Despite these hemostatic changes, no mechanical trauma could be demonstrated after seven days of circulatory support.

Animals↗

Plasmapheresis in HLA-immunosensitized patients prior to kidney transplantation.

Immunosensitization against the human lymphocyte antigen (HLA) is a problem in most transplant centers. It prolongs the waiting list time in addition to risk of frequent acute rejections. To avoid these problems, various pretransplantation approaches have been attempted e.g. plasmapheresis (PP). The present retrospective study reports our experience with PP in this respect over a 5 year period. Twenty-three chronic hemodialysis patients with circulating panel reactive antibodies (> or = 50%) and previous kidney graft rejections were treated with 12 PP each. In addition to this, immunosuppression with cyclophosphamide and prednisolone were administered on the first day of PP and after tapering continued until transplantation. HLA-antibodies, as measured by the panel reactive antibodies and the antibody titer, decreased from about 70% to 30% (p < 0.001) and 5 steps of titerdilution, respectively with PP and immunosuppressive drugs; Twenty-two patients were transplanted with cadaveric grafts. Eight grafts were lost due to irreversible rejection, and one due to the patient's death 2 months after transplantation. The cumulative five-year graft survival at the time of follow-up was 59%. Adequate kidney function (serum creatinine mean 150 mumol/l) was observed in all grafts (n = 3) still functioning 60 months posttransplant. We conclude that pretransplantation plasmapheresis together with immunosuppressive drugs (cyclophosphamide and prednisolone) is useful in the removal of HLA antibodies in immunized patients awaiting kidney transplantation. It can be considered a valuable approach to increase the chances of successful transplantations.

Adult↗

The effect of cadmium on the immune behaviour of guinea pigs with experimental ascariasis.

The subchronic effect of cadmium on selected immunological parameters was studied in guinea pigs with experimental ascariasis. Cadmium chloride given orally for 28 days caused a considerable suppression of T- and B-cells in the lymphoid organs of intoxicated animals, of the metabolic activity of their peritoneal macrophages and a moderate decline in the level of complement CH50 and AH50 from day 1 to day 28 of the experiment, in comparison with the initial value. After a subsequent infection of the subchronically intoxicated guinea pigs the values for both the cell populations and the macrophage metabolic activity remained considerably suppressed, compared with infected control animals. The phagocytic and metabolic activity of macrophages as well as the CH50 and AH50 level, however, increased conspicuously for a short time after application of heavy metal and after infection but it did not reach the level of the infected group. The level of specific circulating antibodies was not affected by intoxication. Compared with the controls, the mean intensity of infection with Ascaris larvae migrating in the lungs of intoxicated animals increased by 20%. The results have established the negative effect of cadmium on the immunological parameters of the cellular immunity and humoral immunity studied and the impairment of the organism's response to the antigenic stimulus after an A. suum infection.

Animals↗

[Study about development of extracapillary blood flow type oxygenator--comparison with HF-4000, Capiox II, and Silox].

Results about comparison of new extracapillary blood flow type polypropylene hollow fiber oxygenator (PHO) with HF-4000, Capiox II and Silox for effects on blood components, hemolysis, immunoglobulin and high molecular weight proteins, such as complements: 1) Platelet protection was about equal. Silox was best in leucocyte protection. 2) PHO was superior to HF-4000. The extracapillary type was better for hemolysis. 3) Silox was best in immunoglobulin protection. Effect on C3 and C4 was equal, and Silox was best in protection of CH50. Slight differences were caused by silicone membrane, not caused by blood flow type. 4) PHO was superior to HF-4000 (commercial extracapillary type), and almost equal to Capiox II (intracapillary type).

Adult↗

[Anti-HCV antibody and hemolytic complement activity in sera from alcoholic patients].

We examined the association of complement activation at a low temperature in vitro with hepatitis C virus infection in alcoholic patients. The incidence of cold activation among these patients was 4.1%, which was higher than the reported incidence of 1.7% among general patients consulting a hospital, and that of 0.5% among donors for blood transfusion. In any population, most cases that showed cold activation were HCV antibody positive. The difference between the incidence of cold activation among HCV antibody positive cases in alcohol high consumers (6/21) and that in control patients (42/103) was regarded as nonsignificant. The higher incidence of cold activation among alcoholic patients may not directly associate with high alcohol consumption and may associate with higher incidence of HCV infection among the group.

Alcoholism↗

[The determination of the fresh fecal contamination of the water of surface reservoirs].

The approbation of a method for the determination of new fecal contamination of water in surface reservoirs has been carried out; in accordance with this method, the presence of new fecal contamination in water is determined by the level of manifestation of the persistence properties (antilysozyme, anticomplementary "anti-interferon" activities) of Escherichia coli, used as a sanitary indicator microorganism.

Complement Hemolytic Activity Assay↗

Prolactin modulates the disease activity of systemic lupus erythematosus accompanied by prolactinoma.

We present a 31-year-old female patient with systemic lupus erythematosus (SLE) which was accompanied by prolactinoma. Her SLE flared when the plasma levels of prolactin (PRL) increased, and subsided when these levels decreased following the administration of bromocriptine, irrespective of the glucocorticoid dosage. For the 29 plasma samples obtained during the clinical course, PRL levels were significantly correlated to the serum anti-DNA antibody titers (r = 0.55, p < 0.05) and inversely to the serum complement activity (r = -0.33, p < 0.05). This result suggests that PRL may play a role in the pathogenesis of SLE in some patients.

Adult↗

Moraxella catarrhalis is only a weak activator of the mannose-binding lectin (MBL) pathway of complement activation.

A hemolytic bystander assay was used to assess the functional serum mannose-binding lectin (MBL) activating capacity of five isolates of Moraxella catarrhalis obtained from children who suffered recurrent acute otitis media episodes. Results showed that this organism is only a poor activator of the lectin pathway of complement activation, with subsequent consequences for the etiology of otitis media by this organism.

Child↗

Interference with total hemolytic complement assay in rheumatoid arthritis: correlation with disease activity.

A subgroup of patients with rheumatoid arthritis (RA) whose sera agglutinated sensitized sheep erythrocytes used for total hemolytic complement determination has been identified. These patients have higher titers of rheumatoid factor (RF) and more severe rheumatoid disease compared to controls. The agglutination of sensitized sheep erythrocytes by sera of some patients with RA may be related to qualitative or quantitative variations in their RF.

Adult↗

Effect of fangchinoline in murine models of multiple organ dysfunction syndrome and septic shock.

OBJECTIVE AND DESIGN: To study the effect of the alkaloid fangchinoline on zymosan-induced multiple organ dysfunction syndrome (MODS) and Escherichia coli (E. coli)-induced septic shock. MATERIAL: Male ICR mice were used. Macrophages were isolated from peritoneal cavity for in vitro study. TREATMENT: Fangchinoline was administered i.p. at a dose of 1 or 5 mg/kg into the mice. METHODS: MODS was induced by intraperitoneal (i.p.) injection of zymosan at a dose 1.0 or 0.8/g b.w. E. coli-induced septic shock was provoked by i.p. inoculation of 5 x 10(8) bacterial cells into mice. TNF-alpha in serum and supernatants from peritoneal macrophages was detected by the use of L-929 cell cytotoxic assay. Alternative pathway (AP) complement activity was determined by hemolytic assay. RESULTS: Fangchinoline increased the survival rate in lethal MODS and septic shock. The alkaloid prevented the loss of body weight and liver enlargement in MODS and suppressed serum tumor necrosis factor-alpha (TNF-alpha) accumulation in MODS and septic shock. CONCLUSIONS: The result suggest that fangchinoline due mainly to its ability to downregulate TNF-alpha production might have protective effect in murine models of zymosan-induced MODS and E. coli-induced septic shock.

Alkaline Phosphatase↗

Bronchoalveolar lavage fluid and serum complement activity in pulmonary sarcoidosis.

In this work, using bronchoalveolar lavage fluids (BALF), we demonstrated the presence of complement within airways by assaying hemolytic activity of the whole classical pathway (CH50) and by measuring the complement component C2 (C2H50). Patients with sarcoidosis, patients with idiopathic pulmonary fibrosis (IPF), and healthy control subjects were compared. No CH50 activity was found in BALF from healthy control subjects (n = 9), but some activity (mean, 20 CH50) was associated with IPF (n = 7). Complement activities ranged from 40 to 554 CH50 in patients with sarcoidosis (n = 27). During the treatment, complement activity decreased in BALF from the few patients in our series who received corticotherapy. C2 hemolytic activity was detected in BALF from the normal control group (in the absence of CH50 activity). In the sarcoidosis and IPF groups when CH50 was present, the variations in the C2/CH50 ratio were studied. The high ratio observed in BALF from patients with sarcoidosis and a chronic derangement of alveolar structure suggests either an increased C2 production or an alternative complement pathway (C2-independent) activation within their lungs.

Adult↗

Biologic activities of poly (2-azaadenylic acid) and poly (2-azainosinic acid).

Poly (2-azaadenylic acid) [(aza2A)n] and poly(2-azainosinic acid [(aza2I)n], two newly synthesized analogues of (A)n and (I)n, in which CH-2 of the purine ring is replaced by a nitrogen atom, have been evaluated in various biological assay systems. (Aza2A) n formed a complex with (U)n and (br5U)n, and (aza2I)n formed a complex with (C)n and (br5C)n, but these complexes were markedly destabilized relative to the corresponding (A)n or (I)n complexes. The (aza2A)n-and (aza2I)n-derived complexes failed to stimulate the production of interferon in primary rabbit kidney cells and human diploid fibroblasts, under conditions (A)n. (U)n, (I)n. (C)n and (I)n. (br5C)n induced high amounts of interferon. both (aza2A)n and (aza2I)n exerted a marked inhibitory effect on the endogenous RNA directed DNA polymerase (reverse transcriptase) activity associated with murine leukemia virus. They caused a relatively mild inhibition of complement activity in an hemolytic assay system.

Aza Compounds↗

Limitation of reperfusion injury by a monoclonal antibody to C5a during myocardial infarction in pigs.

The complement system has been implicated in reperfusion injury during acute myocardial infarction. We therefore attempted to reduce reperfusion injury with a monoclonal antibody (MAb) to the complement component, C5a. In 13 control pigs and 9 pigs pretreated with this MAb, ischemia was induced by a 50-min occlusion of the left anterior descending coronary artery, followed by 3 h of reperfusion. Infarct area (as percent of risk area) was reduced from 58 +/- 5% in controls to 38 +/- 7% (P < 0.05) in MAb-treated animals. Heart rate-systolic blood pressure product, left ventricular (LV) first derivative of pressure, LV end-diastolic pressure, and coronary blood flow were similar (P > 0.05) in the two groups. At 15 min of reperfusion, immunoreactive factor Bb began to increase significantly (P < 0.05) in regional coronary venous plasma, consistent with activation of the alternative complement pathway. The anti-C5a MAb did not attenuate formation of the membrane attack complex (C5b-9) as assessed by a hemolytic complement assay. Myocardial myeloperoxidase activity, a marker of tissue neutrophil concentration, was similar in the risk regions of the two groups, suggesting that neutrophil infiltration was unaltered by the MAb. However, in vitro the MAb (15 and 30 micrograms/ml) reduced C5a-stimulated neutrophil aggregation (67.4 and 70.9%), chemotaxis (52.5 and 81.4%), degranulation (66.7 and 75.8%), and superoxide generation (26.7 and 100%). In conclusion, myocardial infarction-reperfusion is associated with activation of the alternative complement pathway. Furthermore, a MAb to C5a that inhibits neutrophil cytotoxic activity, but neither the membrane attack complex nor myocardial neutrophil accumulation, decreases infarct size in pigs. These data suggest an important role of the alternative complement pathway and C5a in the propagation of ischemia cardiac damage during reperfusion.

Animals↗

Complement activation in patients at risk of developing the adult respiratory distress syndrome.

In this prospective study of 50 patients, 36 of whom developed the adult respiratory distress syndrome (ARDS), early and intense complement activation was demonstrated. These patients were at risk of the ARDS because of multiple injuries, major abdominal surgery, acute pancreatitis, severe burns, or disseminated intravascular coagulation. Abnormal C3 consumption (as measured by the C3d/C3 ratio) and elevated plasma C5a-like activity (as measured by a leukocyte aggregation assay) were associated with, respectively, 84 and 86% of cases of ARDS. Both tests were more sensitive indicators of complement consumption than were assays of total hemolytic complement activity (CH50) or total C3. The C3d/C3 ratio showed a close, inverse correlation with CH50 in 47 healthy subjects, and was increased in 12 control patients after minor surgery. The C5a-like activity was found only in patients at risk of ARDS; it was highly associated with clinical conditions that predispose to the ARDS, but it cannot be considered as a real predictor of ARDS occurrence in these patients. Sequential samples from both sides of the pulmonary circulation showed initial pulmonary clearance followed by the release of C5a-like activity. No simultaneous changes in C3 levels were found, suggesting the possible presence of modulating factors. These observations suggest that other factors (e.g., hypoxia and metabolic cascades) may influence the development of ARDS.

Complement Activation↗