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Biomedical subjects

S Meri

Publications and source records attributed to S Meri.

At least 127 records · Page 7Linked to original sources
PubMed1991

Acute-phase proteins during hemodialysis: correlations with serum interleukin-1 beta levels and different dialysis membranes.

The effects of hemodialysis (HD) on the levels of serum amyloid A (SAA), C-reactive protein (CRP) and interleukin-1 beta (IL-1 beta) were studied in 8 patients. Bicarbonate dialysate was used exclusively, and three different membranes, Cuprophan (CU), cellulose acetate (CA), and polymethylmetachrylate (PMMA) were compared. The SAA levels increased significantly with each membrane. With CU, they rose from 4.0 +/- 2.0 (mg/l, mean +/- SEM) to 9.6 +/- 2.8 at 60 min and to 15.0 +/- 4.9 at 240 min. The values with CA were 3.8 +/- 2.1, 15.3 +/- 5.6, and 23.8 +/- 3.9; and with PMMA 2.4 +/- 1.3, 12.1 +/- 5.6, and 12.1 +/- 5.9, respectively. The alterations of SAA neither correlated with the weight loss nor the increase of serum albumin during dialysis. The CRP values showed insignificant changes. The IL-1 beta levels rose with CU from 87 +/-18 (ng/l) to 155 +/- 33 at 60 min and to 172 +/- 47 at 240 min. With CA, the values were 67 +/- 14, 198 +/- 46, and 121 +/- 23, and with PMMA 63 +/- 13, 246 +/- 93, and 211 +/- 86, respectively. These results did not correlate with the effects of the membranes on complement activation. It is concluded that the release of cytokines during HD apparently leads to a rapid synthesis of acute-phase proteins as a sign of inflammation. Thus, SAA may be used as one indicator of the biocompatibility of HD treatment.

Adult↗
PubMed1991

Distribution of protectin (CD59), a complement membrane attack inhibitor, in normal human tissues.

Protectin (CD59) is a recently discovered 18-20 kDa glycoprotein that effectively inhibits lysis by the membrane attack complex of the homologous complement system. This glycoprotein is widely distributed on the membranes of human blood cells (erythrocytes and leukocytes). By using immunofluorescence microscopy, protectin was observed in vascular endothelia throughout the body and in extravascular tissues. Cells expressing protectin were also found in ductal epithelia of pancreatic, biliary, and salivary systems, bronchi, and kidney collecting ducts. Furthermore, protectin was expressed in the epidermis and in the syncytiotrophoblast of placenta. The expression of protectin in endothelia, in various epithelial cells, and in placenta presumably protects autologous tissues and the fetoplacental unit from complement-mediated damage.

Antigens, CD↗
PubMed1990

Human protectin (CD59), an 18-20-kD homologous complement restriction factor, does not restrict perforin-mediated lysis.

Human protectin (CD59) is an 18-20-kD membrane glycoprotein that restricts lysis of human erythrocytes and leukocytes by homologous complement. By directly incorporating protectin into membranes of heterologous cells we observed that protectin did not prevent perforin-mediated killing, whereas complement killing was effectively restricted. Further, no significant enhancement of cell-mediated killing or target killing by purified perforin was observed with anti-protectin antibodies. Thus, in contrast with complement lysis, restriction of lysis by protectin does not apply to cell-mediated killing.

Animals↗
PubMed1990

A mechanism of activation of the alternative complement pathway by the classical pathway: protection of C3b from inactivation by covalent attachment to C4b.

In this work we studied the role of the classical pathway complement component C4b in the activation of the alternative pathway. It was found that nascent C3b attaches with high efficiency to C4b and that C3b in C4bC3b complexes is protected from inactivation by factors H and I. Activation of C3 by factors B and D in the presence of Mg2+ ions and excess C4b led to 35% incorporation of nascent C3b into C4bC3b complexes in the fluid phase. In comparison, when human IgG was tested as an acceptor under similar conditions, only 12% of generated C3b was incorporated into IgGC3b complexes. The half-life time of dissociation of C3b from purified C4bC3b complexes was approximately 2.3 h at 37 degrees C. C4b in these complexes protected C3b from inactivation as effectively as any known alternative pathway activator. Thus, C3b bound to C4b was tenfold more stable than free C3b or C3b bound to a nonactivating surface. In comparison, the protection provided by attachment to human IgG was only 67% of that of C4b. The results provide an explanation for observations of alternative pathway recruitment following classical pathway activation and for the stability of the classical pathway C5 convertase on surfaces which do not provide protection for C3b from factors H and I.

Complement C3-C5 Convertases↗
PubMed1990

Discrimination between activators and nonactivators of the alternative pathway of complement: regulation via a sialic acid/polyanion binding site on factor H.

The alternative complement pathway is capable of discriminating human cells and tissues from a wide variety of potential pathogens. It has been recently demonstrated that attachment of complement component C3b to activator-derived molecules (e.g., small polysaccharides) restricts inactivation of C3b by factors H and I in a manner similar to activator surfaces. It is now shown that restriction is reversed by certain soluble polyanions (e.g., sialoglycopeptides, heparin, or dextran sulfate) that mimic the effects of sialic acid and glycosaminoglycans on human cells and tissues. Fluid-phase polyanions enhanced binding of factor H to C3b attached to activating particles, indicating that the effect resulted from increased affinity between C3b and factor H. The enhancement was specific for activator-bound C3b since no enhancement was observed on nonactivating particles. While several polyanions could cause this effect, some polyanions could not, indicating specificity. The active polyanions also inhibited lysis of cells via the alternative pathway. The binding site for sialic acid appears to reside on factor H, since factor H bound to heparin-agarose and to sialic acid-bearing fetuinagarose, whereas C3b bound to neither under the same conditions. These observations suggest that occupation of a specific site on factor H by polyanions induces an increase in the C3b-H affinity, resulting in discrimination of host cells and tissues from alternative pathway-activating foreign cells.

Animals↗
PubMed1990

Comparison of hollow fibre membrane oxygenators during cardiopulmonary bypass in children: Dideco Masterflo versus Terumo Capiox II.

This prospective study was planned to compare two different (reversed blood and gaseous compartments) hollow fibre membrane oxygenators, Dideco Masterflo and Terumo Capiox II, in order to find out which of these oxygenators was less injurious during cardiopulmonary bypass (CPB) surgery in small children. Twenty children underwent CPB surgery for complex congenital cardiac malformations. Ten patients were selected for each study group by matching age and weight. Oxygenators were the only variables in the CPB circuit, and special attention was focused on the kinetics of white blood cell count (WBC), complement C3, anaphylatoxin C3a, total haemolytic complement (CH100), C-reactive protein (CRP) and haptoglobin. There were no significant differences between the parameters studied at any sample time. However, there was less intense C3a (peak C3a levels 2506 +/- 1187 SD versus 4302 +/- 3958 SD; p = 0.19) generation, and also less intense CH100 consumption (percentual drop of initial CH100 values was 30% versus 55.2%) in the Dideco Masterflo group of patients. Moreover, postoperative respiratory treatment was somewhat shorter when using Masterflo oxygenators (2.4 +/- 2.41 SD versus 4.0 +/- 2.49 SD days; p = 0.16), although statistical significance was not obtained. These findings may be important in high-risk paediatric patients undergoing open-heart surgery.

Cardiopulmonary Bypass↗
PubMed1990

Acute schistosomiasis mansoni in Finnish hunters visiting Africa: need for appropriate diagnostic serology.

Three symptomatic and 3 asymptomatic patients with acute schistosomiasis mansoni are described. The index case presented with fever and eosinophilia 4-6 weeks after swimming in the Pipi River of the Central African Republic, suggesting acute schistosomiasis (Katayama fever). A fortunate early diagnosis led to early treatment of these schistosomiasis patients. Diagnosis was obtained based on the finding of one Schistosoma mansoni egg in the index case and positive serology in all cases. A commercially available passive haemagglutination test for serum bilharzia antibodies was negative in all cases prior to, and 2 weeks after treatment. However, antibodies against gut-associated antigens (GAA) of adult S. mansoni worms could be demonstrated using the indirect immunofluorescence technique. These cases illustrate the importance of using appropriate diagnostic assays for the early demonstration of infection by schistosomes in previously unexposed "nonimmune" patients with atypical symptoms and in asymptomatic individuals at risk even after brief exposure to schistosome-containing water in endemic countries. Careful (and repeated) stool examination and appropriate serological tests are the keys to prompt diagnosis of S. mansoni infection.

Adult↗
PubMed1990

Human protectin (CD59), an 18,000-20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bilayers.

Human cells are relatively resistant to lysis by the homologous complement system. Here we describe the mechanism of action of a recently discovered and widely distributed 18,000-20,000 molecular weight (MW) membrane glycoprotein (CD59), which appears to act as a major protective element against complement-mediated lysis (hence called protectin). When incorporated into heterologous erythrocyte membranes, protectin efficiently prevented cell lysis by human serum. Neutralization with antibody of the naturally occurring protectin on human erythrocytes or on nucleated K562 cells increased their susceptibility to lysis by homologous complement. During complement activation, protectin became incorporated into the membrane attack complex (MAC). By interacting with newly exposed regions in the C5b-8 complex and in aggregating C9 it limited the number of C9 molecules associating with the C5b-8 complex to a C8:C9 ratio of 1:1.5 instead of a normal average of 1:3.5. The results demonstrate directly that protectin is a powerful inhibitor of complement cytolysis and acts by inhibiting the C5b-8 catalysed insertion of C9 into the lipid bilayer.

Antigens, Differentiation↗
PubMed1990

High frequencies of B8, DR3 and C4A null alleles and immunological disorders in a family of four generations.

In a Finnish family covering four generations many members had immunological symptoms or disorders (mostly skin or joint oriented) with the presence of the B8 antigen positive Major Histocompatibility Complex (MHC) haplotype. Immunological parameters including the presence of autoantibodies, quantitative analysis of the complement components C4, Factor B (BF) and C3 and the serum capacity to inhibit immune precipitation were investigated in relation to the genetic MHC markers. The results showed the importance of the high frequency of the C4A null alleles to these disorders.

Adolescent↗
PubMed1990

Value of C-reactive protein in reflecting the magnitude of complement activation in children undergoing open heart surgery.

The kinetics of C-reactive protein (CRP) were studied prospectively in 30 children (aged 21 days - 16 years) undergoing open heart surgery. CRP was related to the kinetics of total haemolytic complement, complement C3a and postoperative complications. Two (7%) patients died and ten (33%) had postoperative complications. The patients with complications were younger (p less than 0.035), underwent longer perfusions (p less than 0.001) and had longer aortic cross-clamping times (p less than 0.003). The mean peak CRP level after surgery (108 mg/l) was reached, on the average, in 43 h. No statistical difference in CRP concentrations was found between the complication and non-complication groups. Extensive complement activation was seen in every patient. CRP did not reflect the magnitude of complement activation induced by cardiopulmonary bypass. The patient sample was too small to draw reliable conclusions about the value of CRP in detecting postoperative complications after open heart surgery in children.

Adolescent↗
PubMed1989

Plasmin and fibronectin degradation in chronic secretory otitis media.

Mucoid effusions from 39 children with secretory otitis media, altogether 42 specimens, were analyzed for proteolytic activity using radial caseinolysis procedures, for fibronectin using a solid-phase enzyme immunoassay, and for fibronectin fragmentation using immunoblotting. All samples contained proteolytic activity, tentatively identified as plasmin on the basis of comigration with purified human plasmin in zymographic analysis. In 19 specimens the plasmin level exceeded 1 microgram/mg of protein; the highest value recorded was 18.7 micrograms/mg. Low levels of net plasminogen activator activity were found in 12 specimens and identified as urokinase according to comigration with the urokinase standard in zymography. Fibronectin was detected in all but one of the 42 specimens; in seven specimens the levels exceeded those in normal plasma, calculated per milligram of total protein. Extensive fragmentation of fibronectin was found in 19 specimens, correlating with high plasmin levels. The results are indicative of an ongoing proteolytic process in secretory otitis media and suggest that plasmin-caused degradation of the fibronectin-containing basement membrane and subsequent formation of granulation tissue may be involved in the development of adhesive middle ears.

Child↗
PubMed1988

Complement activation and HLA-B27.

The efficiency of complement activation was studied in sera from HLA-B27 positive and negative subjects (27 with previous yersinia arthritis and 35 controls). Activation of complement with zymosan induced higher mean levels of the anaphylatoxin C3a in HLA-B27 positive sera (mean (SD) 7.40 (1.66) mg/l) than in HLA-B27 negative sera (6.41 (1.79) mg/l). Similarly, higher levels of C3d,g, another C3 breakdown fragment, were obtained in HLA-B27 positive sera after Escherichia coli 0111:B4 lipopolysaccharide treatment (17.6 (3.7)% v 15.0 (3.8)%). The differences occurred irrespective of previous arthritis, complement C4 or Bf phenotype, or variation in background complement levels. The findings suggest that an increased responsiveness to complement activators may contribute to the pathogenesis of HLA-B27 associated inflammatory diseases.

Adult↗
PubMed1988

Complement activation during cardiopulmonary bypass in children.

Complement activation was evaluated prospectively in serial serum and plasma samples from 30 children, who underwent cardiopulmonary bypass operations. Each patient showed a decrease in total hemolytic C levels and increase in C3 activation product (C3a desArg and C3bi/c) levels. In 11 of the 30 patients surgery was associated with a complication: death (2), respiratory failure (RF, 9), septicaemia (4), postpericardiotomy syndrome (PPS, 1) and pancreatitis (1). Patients suffering from RF were younger, underwent longer perfusions and had somewhat more extensive changes in the C system, although no direct correlation between high C3a desArg levels and RF existed. Instead, the increase in C3a desArg was in linear correlation with the perfusion time. Most complications during the latter postoperative period were associated with distinct episodes of lower grade C activation.

Cardiopulmonary Bypass↗
PubMed1988

Organ-specific autoimmunity and HLA-DR antigens as markers for beta-cell destruction in patients with type II diabetes.

Islet cell antibodies (ICAs), thyrogastric antibodies, and HLA-DR antigens were determined in 204 patients with type II (non-insulin-dependent) diabetes controlled with diet and/or oral hypoglycemic agents (NIR) and in 108 age-matched patients who required insulin to control their hyperglycemia (IR). beta-Cell function measured as C-peptide response to glucagon was evaluated in relation to the presence of ICAs and HLA-DR antigens. The IR patients differed from the NIR patients with respect to higher frequency of ICAs (P less than .001), thyroid antibodies (P less than .02), and the HLA antigen DR4 (P less than .02). The highest frequency of ICAs and thyroid antibodies was observed in female insulin-treated subjects (51.2 and 46.4%). Patients who were heterozygous for HLA-DR3/DR4 showed significantly higher frequency of ICAs (P less than .01) and complement-fixing ICAs (P less than .001) than patients without the heterozygous form DR3/DR4. Neither the presence of ICA alone nor DR3/DR4 alone was associated with a significant impairment of beta-cell function. However, when both ICA and DR3/DR4 were present in a diabetic individual, beta-cell function was markedly impaired (P less than .001), suggesting that both genetic and autoimmune factors are necessary to facilitate the process leading to beta-cell destruction of the patients. Our findings suggest that type II diabetes is a heterogeneous disorder including at least two major subgroups, which can be further characterized by HLA-DR antigens and organ-specific antibodies.

Autoantibodies↗
PubMed1986

Human tumor cells synthesize and secrete alpha-2-macroglobulin in vitro.

In previous studies we showed that human sarcoma and melanoma cell lines synthesize and secrete into culture medium a glycoprotein, migrating in urea sodium dodecyl sulfate-polyacrylamide gel electrophoresis at Mr 140,000. It is not detected in cultures of the corresponding normal cells. Conditioned medium of the melanoma cell line HMB-2, producing among the cell lines tested the largest amounts of this glycoprotein, has now been used as a source for purification of the protein. NH2-terminal amino-acid sequence determination of the purified glycoprotein showed that it is identical to human alpha 2-macroglobulin (alpha 2M). Rabbit antibodies raised against the glycoprotein specifically reacted in immunoblotting and immunodiffusion tests with alpha 2M present in human plasma. Likewise, these antibodies immunoprecipitated from the conditioned media of 35S-methionine-labelled melanoma and osteosarcoma cell lines the protein which had a molecular weight corresponding to alpha 2M. alpha 2M was also synthesized and secreted by 2 strains of fetal lung fibroblasts but not by fetal skin fibroblasts or adult skin fibroblasts autologous to the osteosarcoma cell line.

Cells, Cultured↗
PubMed1985

Complement activation by antigenic fractions of Entamoeba histolytica.

Complement (C) activation induced by Entamoeba histolytica in normal non-immune human serum was studied by testing in vitro the ability of different fractions of the trophozoites to cause C3 breakdown. Whole trophozoites were found to activate both alternative and classical C pathways. The antibody-independent classical pathway (MgEGTA inhibitable) C activating capacity was found to greatly increase after disruption of the cell membrane by sonication. Subsequent analysis after differential centrifugation and ion exchange chromatography of the membrane/particulate fractions showed, that this activity was not due to DNA, which has been shown to have the similar characteristics, but to other, as yet unidentified components. A rather homogenous membrane fraction obtained by elution with 0.4 M Tris-HCl, pH 8.1 (described as 4M) and some cytoplasmic constituents obtained after gel chromatography retained a moderate degree of alternative pathway C3 activating capacity seen with intact trophozoites. Thus, it seems, that serum contact to the outer surface of E. histolytica trophozoites leads to C activation via both pathways with cell death as the result and to subsequent release of more efficiently classical pathway activating components. These phenomena probably have an important role in the inflammatory process in invasive amoebiasis.

Animals↗
PubMed1985

Complement levels and C3 breakdown products in open-heart surgery: association of C3 conversion with the postpericardiotomy syndrome.

The role of the complement system in the pathogenesis of the post-pericardiotomy syndrome (PPS) was evaluated in a prospective study by measuring the levels of complement (C) components, total haemolytic complement activity and circulating C3 breakdown products in serial plasma and serum samples of 45 patients undergoing open-heart surgery. A consistent reduction in the levels of C3 and C4 but not of factor B was seen on the second post-operative day. During the second post-operative week the antigenic levels of each C component increased significantly. At this time six patients developed the post-pericardiotomy syndrome. Circulating C3 conversion products (C3bi and C3c) were demonstrated in the plasma samples from five of these patients by the immunofixation technique, the mean conversion percentage being 14.3 +/- 10.6. The samples from 15 of the 39 other patients also showed C3 conversion, but the mean percentage was significantly lower (4.5 +/- 6.1%, P less than 0.05). Before the second post-operative week C3 conversion was rare in both groups. The C3d levels of plasma samples, as detected by rocket immunoelectrophoresis, followed a similar pattern. Reduced total haemolytic complement activity was found in three patients suffering from the PPS. These results suggest a role for complement in the non-infectious, inflammatory response during the late post-operative period after open heart surgery, and especially in the post-pericardiotomy syndrome.

Adolescent↗