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PubMed1988

Mitochondrial function in rats is affected by modification of membrane phospholipids with dietary sardine oil.

Phospholipids of heart and liver of rats fed a diet containing sardine oil had more omega 3 polyunsaturated fatty acids and less omega 6 polyunsaturated fatty acids than those of rats fed corn oil, whereas there was little difference in the fatty acid composition of brain phospholipids. The mass of phospholipid classes in rat heart mitochondria was not changed, but their fatty acid compositions were altered. Modification of the fatty acid compositions of mitochondrial phosphatidylcholine and phosphatidylethanolamine reached a plateau after 10 d of feeding, but that of cardiolipin continued for 30 d. The O2 consumption rate of rat heart mitochondria decreased as the fatty acid composition of the phospholipids changed. This may be due to the reduction of the activity of cytochrome c oxidase, which requires cardiolipin for its activity. However, F1F0-ATPase, which also requires cardiolipin, was activated under the same conditions.

Animals↗
PubMed1998

Association of anticardiolipin antibodies with intraglomerular thrombi and renal dysfunction in lupus nephritis.

We studied positivity for anti-cardiolipin antibody, intraglomerular capillary thrombi on renal biopsy, and the progression of renal disease in 51 patients (10 male and 41 female), mean age 37 years (range 17-65 years), with a diagnosis of systemic lupus erythematosis and clinically evident nephritis confirmed by renal biopsy. Serum creatinine, serum indicators of disease activity and biopsies were analysed in subgroups according to thrombi and anticardiolipin status. End-points were death or chronic dialysis requirement and survival. Degree of sclerosis, crescent formation and necrosed glomeruli were all greater in those specimens positive for thrombi and in those specimens of patients who were serum ACA-positive, suggesting a relationship to disease activity/severity at presentation. The increase in serum anti-DNA antibodies and ANA and the reduction in C3 and C4 were significant in ACA-positive patients, with a strong relationship to disease activity when compared with changes in the ACA-negative patients (p < 0.05 in all cases). There was no significant difference when patients were separated according to the presence or absence of thrombi. Renal function at presentation was worse in patients with intracapillary thrombi and ACA positivity (p = 0.085 and p = 0.042, respectively). All patients progressed, but only those with intracapillary thrombi or anti-cardiolipin antibody positivity had a significant deterioration in renal function. Twenty-one thrombotic episodes occurred in 14 patients, of whom 13 were ACA-positive. Anticardiolipin antibody is a strong predictor of the presence of intraglomerular thrombi in SLE patients with renal involvement. The presence of thrombi and/or anticardiolipin antibodies indicate a worse long-term renal outcome. Anti-cardiolipin antibody positivity is a strong predictor of systemic vascular thrombotic complications.

Adolescent↗
PubMed1993

Autoantibodies in malaria, tuberculosis and hepatitis B in a west African population.

Following reports of associations between autoantibodies and living in the tropics, we have studied the seroprevalence and nature of anti-nuclear antibodies, anti-cardiolipin antibodies, antibodies to extractable nuclear antigens and anti-neutrophilic cytoplasmic antibodies in 351 West Africans with malaria, tuberculosis or hepatitis B, or in good health. Amongst healthy West Africans we found a seroprevalence of 7% for anti-nuclear antibodies with several staining patterns, and of 30.3% for anti-cardiolipin antibodies. Among patients with tuberculosis and malaria there was twice that frequency of anti-nuclear antibodies (predominantly speckled in pattern), and anti-neutrophil cytoplasmic antibodies (predominantly IgM) were demonstrated in a few cases. A possible association between IgG anti-cardiolipin antibodies and tuberculosis was observed (P < 0.05), but antibodies to double-stranded DNA were not elevated and no antibodies to extractable nuclear antigens were found in any of the patients or healthy individuals studied. Our findings suggest the need for caution in the interpretation of autoantibody tests in subjects from or living in the tropics, as well as in patients with tropical infections.

Acute Disease↗
PubMed1994

IgG2 subclass restriction of anti-beta 2 glycoprotein 1 antibodies in autoimmune patients.

The IgG subclass and light chain distribution of antiphospholipid antibodies (aPL) occurring in autoimmune patients were determined by means of two radioimmunoassays using either cardiolipin- or beta 2 glycoprotein 1 (beta 2GP1)-coated microtitre plates and mouse MoAbs. Of 50 sera selected for positivity of anticardiolipin antibodies (ACA) of the IgG isotype, 32 (64%) possessed anti-beta 2GP1 antibodies and their presence was closely associated with clinical features of the antiphospholipid syndrome. Good correlations were found between ACA and anti-beta 2GP1 antibodies when considering antibody level and patterns of light chain and IgG subclass, suggesting that, overall, the same antibodies were being measured. Light chain analysis showed the polyclonal origin of these antibodies and, in most sera, a trend towards use of lambda chain. Among sera positive for anti-beta 2GP1 antibodies, IgG2 was the major subclass reactive with beta 2GP1 and cardiolipin (87% and 74% of the IgG antibody activity, respectively). In contrast, in the group of 18 sera lacking anti-beta 2GP1 antibodies, ACA were largely restricted to IgG3, with a lesser contribution by IgG1. A few selected sera from the anti-beta 2GP1-positive group were shown to contain mixtures of antibodies that required beta 2GP1 (restricted to IgG2 present in large amounts) and did not require this cofactor (restricted to IgG3 and/or IgG1 present in low amounts) for their reactivity with cardiolipin. There was no contribution of glycosylation to the epitopes recognized by anti-beta 2GP1 antibodies, even though human anti-carbohydrate antibodies are restricted to the IgG2 subclass. These findings further emphasize the intra- and interindividual heterogeneity of aPL, and should help to discriminate clinically relevant specificies.

Adolescent↗
PubMed1982

Kinetic and structural differences between cytochrome c oxidases from beef liver and heart.

1. The cytochrome content of beef liver mitochondria differs from that of beef heart mitochondria by an eightfold lower cytochrome aa3 and a twofold lower cytochrome b and c + c1 content. 2. The kinetic properties of cytochrome c oxidases from beef liver and heart were measured with intact cytochrome c-depleted membranes, deoxycholate-dissolved membranes, and with the isolated enzymes at various cytochrome c concentrations with an oxygen electrode. Under all conditions a higher V was found for the liver enzyme, both for the low-affinity and for the high-affinity binding site for cytochrome c. Differences were also found for the Km of the two enzymes. 3. Isolated beef heart mitochondria contained about twice as much cardiolipin than beef liver mitochondria. The isolated enzymes contained one mole cardiolipin per mole of the heart enzyme, but 2 moles cardiolipin per mole of the liver enzyme. 4. By application of a high performance sodium dodecylsulfate gel electrophoretic system the two isolated enzymes could be separated into 13 different protein components, three of which (polypeptides VIa, VIIa and VIII) were found to differ in their apparent molecular weights. The functional meaning of cytochrome c oxidase isoenzymes in liver and heart is discussed.

Animals↗
PubMed1996

Antiphospholipid antibodies in patients with preeclampsia.

PROBLEM: To determine the incidence of anticardiolipin and antiphosphatidylserine antibodies in women with preeclampsia. METHODS: Sera from 100 women with preeclampsia and 100 normotensive pregnant women in the third trimester were assayed for anticardiolipin and antiphosphatidylserine antibodies. RESULTS: Antiphosphatidylserine antibodies were positive for IgM in 1 patient (1%) and for IgG in 4 patients (4%). IgM antibodies to cardiolipin were positive in two patients (2%) while IgG antibodies to cardiolipin were positive in nine patients (9%). Only 3% of the control women were positive for antiphospholipid antibodies. None of the patients or controls had positive levels of IgA anticardiolipin or antiphosphatidylserine antibodies. CONCLUSIONS: Elevated levels of IgG or IgM antibodies to cardiolipin and phosphatidylserine were detected in 11/100 (11%) of women diagnosed with preeclampsia in the third trimester compared to only 3/100 (3%) positive in controls (P < or = 0.05). These findings suggest that antiphospholipid antibodies may play a pathogenic role in some women with preeclampsia.

Adolescent↗
PubMed1998

Correlation between beta 2-glycoprotein antibodies and antiphospholipid antibodies in patients with reproductive failure.

PROBLEM: Antiphospholipid antibodies (APAs) are important in the etiology of reproductive failure. Studies have shown that binding proteins are necessary for the detection of APAs. One of these, beta 2-glycoprotein, has been shown to be necessary for detection of anticardiolipin antibodies. It is felt that some APAs may be directed to the binding protein itself, or to a combination of the binding protein and phospholipid. METHOD OF STUDY: In this study, a comparison of APAs vs. anti beta 2-glycoprotein antibodies was performed on the sera of 123 women younger than 40 years of age with a history of reproductive failure. Antibodies to six phospholipid epitopes, cardiolipin, phosphatidyle-thanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, phosphatidylglycerol, and phosphatidylserine, were measured. RESULTS: Of the 123 women tested, 33 had one or more positive immunoglobulin (Ig)G antibodies to phospholipids, of which 9 were to cardiolipin. However, only 1 of 123 women had IgG antibodies to beta 2-glycoprotein and she was APA negative. Thirty-eight of 123 women had one or more IgM antibodies to phospholipids, with none directed to cardiolipin IgM. In contrast, only 8 of the 123 women had IgM antibodies to beta 2-glycoprotein. Five of the eight patients had IgM APA; 4 of 5 had IgM antibodies to PE, 1 to PI. CONCLUSIONS: There is no correlation between beta 2-glycoprotein antibodies and APA status in this population. To date, our most sensitive test for detecting phospholipid autoimmune-mediated in vitro fertilization failure still appears to be the ELISA assay for APA.

Adult↗
PubMed1983

Interaction of sn-glycerol 3-phosphorothioate with Escherichia coli: effect on cell growth and metabolism.

sn-Glycerol 3-phosphorothioate was found to be bacteriocidal to strains of Escherichia coli which have a functional sn-glycerol 3-phosphate transport system. This effect was manifest in strains 7 and 8, which are constitutive mutants for the utilization and transport of sn-glycerol 3-phosphate (glpRc2). Strain E15, which is considered to be wild type for the glycerol phosphate functional units, was affected by the phosphorothioate analog only under conditions that are known to induce the transport system for sn-glycerol 3-phosphate. In addition, another strain of E. coli, strain 6, which is isogenic with strain E15 but has an impaired sn-glycerol 3-phosphate transport system (glpT13), was not affected by similar concentrations of sn-glycerol 3-phosphorothioate. Transport studies in which [3H]glycerol phosphate and its phosphorothioate analog were used demonstrated that the latter compound was taken up via the specific active transport system for sn-glycerol 3-phosphate; the Km values were 9 and 11 microM, respectively. The rates of macromolecular synthesis were found to be inhibited severely by sn-glycerol 3-phosphorothioate at a concentration at which sn-glycerol 3-phosphate had no effect (5 microM). At a lower concentration of the analog (0.5 microM), the rates of protein synthesis and RNA synthesis (52 and 58% below control values after 90 min, respectively) were more sensitive than the rates of DNA synthesis and cell wall synthesis (18% below control values after 3 h for DNA; transient decrease in the cell wall values after 90 min). The levels of the nucleoside triphosphates were not affected by the presence of the phospholipid precursor or its analog at a concentration of 5 microM. The phospholipid composition was significantly altered in the presence of bacteriocidal concentrations (5 microM) of sn-glycerol 3-phosphorothioate. The amount of phosphatidylglycerol in the membranes decreased from 13.5 to 3.5%. Concomitant with this decrease in phosphatidylglycerol content was a fourfold increase in the 32P content of cardiolipin (from 6.8 to 24.2%), whereas the phosphatidylethanolamine content showed only a minor reduction (8%) after 3 h. The rates of synthesis of all of the phospholipids decreased in the presence of 5 microM sn-glycerol 3-phosphorothioate, with the most significant effects observed for phosphatidylglycerol (63% after 3 h). Phosphatidylglycerol showed increased rates of turnover after 90 min (21%) and 3 h (11%), with concomitant increases in the levels of cardiolipin of more than twofold. Our data suggest that a considerably greater proportion of phosphatidylglycerol turnover may be recover in cardiolipin than is metabolized via other pathways (e.g., the membrane-derived oligosaccharide pathway).

Biological Transport↗
PubMed1997

Lipid and fatty acid composition of cytoplasmic membranes from Streptomyces hygroscopicus and its stable protoplast-type L form.

The cells of an L-form strain of Streptomyces hygroscopicus have been grown for 20 years without a cell wall. Their cytoplasmic membranes have high stability and an unusual structural polymorphism. To clarify the importance of the lipid components for these membrane properties, a comparative analysis has been carried out with purified membranes of L-form cells, of parent vegetative hyphal cells (N-form cells), and of protoplasts derived from the latter. The phospholipid classes and fatty acids were determined by thin-layer chromatography (TLC), two-dimensional TLC, high-performance liquid chromatography, gas chromatography, and mass spectrometry. The qualitative compositions of cardiolipin (CL), lyso-cardiolipin (LCL), phosphatidylethanolamine (PE1 and PE2), lyso-phosphatidylethanolamine (LPE), phosphatidylinositolmannoside (PIM), phosphatidic acid (PA), dilyso-cardiolipin-phosphatidylinositol (DLCL-PI), and the 13 main fatty acids were the same in the three membrane types. However, significant quantitative differences were observed in the L-form membrane. They consist of a three- to fourfold-higher content of total, extractable lipids, 20% more phospholipids, an increased content of CL and PIM, and a reduced amount of the component DLCL-PI. Furthermore, the L-form membrane is characterized by a higher content of branched anteiso 15:0 and anteiso 17:0 fatty acids compared to that of the membranes of the walled vegetative cells. These fatty acids have lower melting points than their straight and iso-branched counterparts and make the membrane more fluid. The phospholipid composition of the protoplast membrane differs quantitatively from that of the N form and the L form. Whereas the phospholipid classes are mostly similar to that of the N form, the fatty acid pattern tends to be closer to that of the L-form membrane. The membranes of both the L-form cells and the protoplasts need to be more fluid because of their spherical cell shape and higher degree of curvature compared with N-form membranes.

Cell Membrane↗
PubMed1968

Lipids of Salmonella typhimurium and Escherichia coli: structure and metabolism.

The nature and quantity of the phospholipids of Salmonella typhimurium and Escherichia coli K-12 have been examined. The main classes of phospholipids, phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin have been completely characterized. Four minor compounds have been detected: phosphatidylserine, phosphatidic acid, and two partially characterized lipids. The phospholipid composition of the two organisms is quite similar, the only difference is the absence of one of the minor components and a decreased level of all components in E. coli. A study of the turnover of the phosphate in the phospholipids demonstrated no turnover in phosphatidylethanolamine, a slow turnover in phosphatidylglycerol, and a slow turnover in cardiolipin with, possibly, a transfer of phosphate from phosphatidylglycerol to cardiolipin. The amino acid phenylalanine is shown to become incorporated intact into lipidic compounds which have been partially characterized. Methods for the isolation and separation of lipids have been examined for their utility with these bacteria.

Autoradiography↗
PubMed1968

Phospholipid alterations during growth of Escherichia coli.

As cultures of Escherichia coli progressed from the exponential growth phase to the stationary growth phase, the phospholipid composition of the cell was altered. Unsaturated fatty acids were converted to cyclopropane fatty acids, and phosphatidyl glycerol appears to have been converted to cardiolipin. With dual isotope label experiments, the kinetics of synthesis of cyclopropane fatty acid for each of the phospholipids was examined in vivo. The amount of cyclopropane fatty acid per phospholipid molecule began to increase in phosphatidyl ethanolamine at a cell density below the density at which this increase was observed in phosphatidyl glycerol or cardiolipin. The rate of this increase in phosphatidyl glycerol or in cardiolipin was faster than the rate of increase in phosphatidyl ethanolamine. After a few hours of stationary-phase growth, all the phospholipids were equally rich in cyclopropane fatty acids. It is suggested that the phospholipid alterations observed are a mechanism to protect against phospholipid degradation during stationary phase growth. Cyclopropane fatty acid synthetase activity was assayed in cultures at various stages of growth. Cultures from all growth stages examined had the same specific activity in crude extracts.

Autoradiography↗
PubMed1968

Lipid composition of the electron transport membrane of Haemophilus parainfluenzae.

The principal lipids associated with the electron transport membrane of Haemophilus parainfluenzae are phosphatidylethanolamine (78%), phosphatidylmonomethylethanolamine (0.4%), phosphatidylglycerol (18%), phosphatidylcholine (0.4%), phosphatidylserine (0.4%), phosphatidic acid (0.2%), and cardiolipin (3.0%). Phospholipids account for 98.4% of the extractible fatty acids. There are no glycolipids, plasmalogens, alkyl ethers, or lipo amino acid esters in the membrane lipids. Glycerol phosphate esters derived from the phospholipids by mild alkaline methanolysis were identified by their staining reactions, mobility on paper and ion-exchange column chromatography, and by the molar glycerol to phosphate ratios. Eleven diacyl phospholipids can be separated by two-dimensional thin-layer chromatography. Each lipid served as a substrate for phospholipase D, and had a fatty acid to phosphate ratio of 2:1. Each separated diacyl phospholipid was deacylated and the glycerol phosphate ester was identified by paper chromatography in four solvent systems. Of the 11 separated phospholipids, 3 were phosphatidylethanolamines, 2 were phosphatidylserines, and 2 were phosphatidylglycerols. Phosphatidylcholine, cardiolipin, and phosphatidic acid were found at a single location. Phosphatidylmonomethylethanolamine was found with the major phosphatidylethanolamine. Three distinct classes of phospholipids are separable according to their relative fatty acid compositions. (i) The trace lipids consist of two phosphatidylethanolamines, two phosphatidylserines, phosphatidylcholine, phosphatidic acid, and a phosphatidylglycerol. Each lipid represents less than 0.3% of the total lipid phosphate. These lipids are characterized by high proportions of the short (C(10) to C(14)) and long (C(19) to C(22)) fatty acids with practically no palmitoleic acid. (ii) The major phospholipids (93% of the lipid phosphate) are phosphatidylethanolamine, phosphatidylmonomethylethanolamine, and phosphatidylglycerol. These lipids contain a low proportion of the short ( C(19)) fatty acids. Palmitic and palmitoleic acids represent over 80% of the total fatty acids. (iii) The fatty acid composition of the cardiolipin is intermediate between the other two classes. Both palmitoleic and the longer fatty acids represent a significant proportion of the total fatty acid.

Chemistry Techniques, Analytical↗
PubMed2000

Anti-ribosomal P protein antibodies detected by immunoblotting in patients with connective tissue diseases: their specificity for SLE and association with IgG anticardiolipin antibodies.

OBJECTIVE: To assess the prevalence and clinical and serological associations of anti-ribosomal P protein antibodies (anti-P antibodies) in patients with connective tissue diseases (CTDs) and investigate the immunobiological nature of autoantibody clustering in which anti-P antibodies play a part. METHODS: IgG anti-P antibodies in the sera of 267 patients with CTDs and 31 healthy subjects were analysed by immunoblotting performed on cytoplasmic extract of Raji cells. 60 patients with systemic lupus erythematosus (SLE), 32 systemic sclerosis, 46 primary Sjögren's syndrome, 16 poly/dermatomyositis, 11 rheumatoid arthritis, 8 undifferentiated CTD, 72 overlap CTD, and 22 primary antiphospholipid syndrome were studied. Anti-P antibodies were affinity purified by elution from nitrocellulose bound antigen and tested by ELISA for their binding activity to cardiolipin. RESULTS: Anti-P antibodies were detected in 16 (6%) patients and in none of the controls: 12/60 SLE (20%) and 4/80 undifferentiated/overlap patients with CTD (5%). A close association of IgG antibodies with P proteins and with cardiolipin was seen in lupus sera (p=0.0009, odds ratio 18.33). Anti-P antibodies from 9 of 12 anti-P lupus serum samples could be affinity purified and none of the affinity purified fractions cross reacted with ELISA plate coated cardiolipin. CONCLUSIONS: Anti-P immunoreactivity is a specific marker of SLE and lupus-like disease and its detection is recommended as a powerful diagnostic tool. Anti-P antibodies are strongly clustered with IgG anticardiolipin antibodies in lupus sera, even if they are independently elicited. This suggests that their cognate autoantigens play a part in a common pathogenetic pathway in SLE.

Antibodies, Anticardiolipin↗
PubMed1976

Evaluation of automated large-scale screening tests for syphilis.

Two methods of performing serological screening tests for syphilis are compared. One consisted of the Venereal Diseases Reference Laboratory (VDRL) slide test, the cardiolipin Wassermann reaction (CWR), and the Reiter protein complement fixation test (RPCFT) performed manually; the other was a fully automated system using two Technicon AutoAnalyzers (AAII), one for the automated reagin test (ART) and the other for automated complement fixation tests. The absorbed fluorescent treponemal antibody test (FTA-ABS) was used as a final arbiter in all cases found to be seropositive by either method. A pooled antigen consisting of a mixture of cardiolipin and Reiter protein was used for the automated complement fixation test, thus increasing the scope and capacity of the system. The AutoAnalyzer was shown to be capable of performing 400 cardiolipin and Reiter complement fixation tests and 700 automated reagin tests in an 8-hour day. Modification of the complement fixation test method to take advantage of the highly sensitive colorimeter resulted in a significant increase in sensitivity and a corresponding saving in reagents. Of the 7843 sera tested, 258 gave a positive result in one or more of the screening tests. The automated test detected many more Reiter positive sera (127) than the manual test (83). Conversely, fewer CWR positive sera were detected by the automated test (60) than by the manual test (82). There was little difference between the number of positive sera detected by the ART (73) and the VDRL slide test (71). In 19 instances the automated tests detected positive sera which registered as completely negative in the manual tests, and four seropositive cases which the automated tests had failed to detect were detected by the manual tests, and four seropositive cases which the automated tests had failed to detect were detected by the manual tests. It was concluded that a combination of the ART and automated Reiter protein complement fixation test (ARPCFT) would be ideal for use in a large-scale screening programme for the detection of syphilis.

Autoanalysis↗
PubMed2004

Attenuation of fatty acid-induced apoptosis by low-dose alcohol in neonatal rat cardiomyocytes.

Moderate alcohol consumption has been shown to reduce the morbidity and mortality from coronary heart disease. Ethanol elicits its protective effects via mechanisms that include activation of protein kinases linked to growth and survival. Our results in isolated neonatal rat cardiomyocytes demonstrate that repeated short-term, low-dose exposure to ethanol is sufficient to activate the growth and/or survival pathways that involve PKC-epsilon, Akt, and AMP-activated kinase. In addition, we are able to induce apoptosis in these cardiomyocytes using the saturated fatty acid palmitate. Pretreatment with multiple low-dose ethanol exposures attenuates the apoptotic response to palmitate. This protection is manifested by a reduction in caspase-3-like activity, decreased mitochondrial loss of cytochrome c, and decreased loss of the mitochondrial lipid cardiolipin. We previously reported that incubation of cardiomyocytes with palmitate results in decreased production of reactive oxygen species compared with cells incubated with the nonapoptotic fatty acid oleate. In the present study, we observed an increase in the production of superoxide and the rates of fatty acid oxidation in cardiomyocytes pretreated with ethanol and then exposed to fatty acids. The level of superoxide production in palmitate-treated cells returns to the levels observed in oleate-treated cells after ethanol exposure. Taken together with our observed increase in AMP-activated kinase activity, we propose that ethanol pretreatments stimulate oxidative metabolism and electron transport within cardiomyocytes. We postulate that stimulation of palmitate metabolism may protect cardiomyocytes by preventing accumulation of unsaturated precursor molecules of cardiolipin synthesis. Maintaining cardiolipin levels may be sufficient to prevent the mitochondrial loss of cytochrome c and the downstream activation of caspases.

AMP-Activated Protein Kinases↗
PubMed1992

Hematogenous factors and prediction of delayed ischemic deficit after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Delayed ischemic deficits contribute to the high morbidity and mortality rates associated with subarachnoid hemorrhage. We evaluated the potential usefulness of measuring coagulation and hemorheological variables and cardiolipin antibodies for prediction of delayed ischemic deficit after subarachnoid hemorrhage. METHODS: Consecutive patients with subarachnoid hemorrhage were studied. Coagulation and hemorheological variables and cardiolipin antibodies were measured on admission, within 7 days of subarachnoid hemorrhage. A subset of patients was studied on admission and at two subsequent occasions. RESULTS: Sixty-nine patients were studied. Sixty-one of these were without clinical manifestations of vasospasm at admission, and 16 developed delayed ischemic deficit during their hospitalization. None of the laboratory variables measured were significantly different between patients with or without later development of delayed ischemic deficit. Elevation of the fibrin fragment D-dimer was found in the group of eight patients admitted with ischemic symptoms and in 49% (34 of 69) of all patients, but this was not associated with delayed ischemic deficit. Sixteen patients were studied on three occasions; this group showed a significant decrease in hematocrit, an increased white blood cell count, and no change in fibrinogen concentration. Fibrin D-dimer levels rose significantly after surgery (from 5.01 +/- 0.69 to 5.53 +/- 0.58 ln-ng/ml, p less than 0.025) and after onset of delayed ischemic deficit (from 4.71 +/- 0.64 to 5.84 +/- 0.34 ln-ng/ml, p less than 0.01). CONCLUSIONS: Hemostatic measurements, hemorheological variables, and cardiolipin immunoreactivity did not predict delayed ischemic deficit in this population.

Adult↗
PubMed1998

High prevalence of antiphosphatidylinositol antibodies in young patients with cerebral ischemia of undetermined cause.

BACKGROUND AND PURPOSE: Anticardiolipin antibodies (aCL) are associated with thrombotic phenomena including cerebral ischemia in young adults. Although aCL are directed to a neoepitope formed by phospholipid and beta2-glycoprotein I (beta2-GPI), immunoassays based on cardiolipin as target antigen are widely used. We previously demonstrated that 47% of aCL-negative systemic lupus erythematosus (SLE) patients had antiphospholipid antibodies (aPL) to epitopes other than cardiolipin, and we found an association between aPL to noncardiolipin antigens and thrombosis. We now assess the prevalence and clinical significance of noncardiolipin aPL in young adults with cerebrovascular disease of undetermined etiology. METHODS: Seventy-seven non-SLE patients, aged <51 years, with cerebral ischemia were studied. Specificity of aPL were characterized by ELISAs using 7 different phospholipids: cardiolipin (CL), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (PA), phosphatidylcholine, and phosphatidylethanolamine. RESULTS: Thirty-four patients (44.1%), had aPL to 1 or more of the following antigens: 23.4% to CL, 18.2% to PS, 15.6% to PG, 14.3% to PA, and 28.6% to PI. Fifty-nine patients (76.6%) were aCL negative. Of these subjects 23.4% showed aPL to noncardiolipin epitopes. PI was the specificity with highest prevalence in all subgroups, and in 6 patients anti-PI antibodies were the only detectable aPL. The binding of aPL to the different antigens was beta2-GPI dependent. CONCLUSIONS: Our data demonstrate a high prevalence of aPL in young adults with cerebral ischemia of undetermined cause. PI was the specificity with highest prevalence, suggesting that anti-PI antibodies may be an immunological marker in young patients with cerebrovascular disease.

Adult↗
PubMed1997

Effect of beta 2glycoprotein I and human monoclonal anticardiolipin antibody on the protein S/C4b-binding protein system.

The effect of beta 2glycoprotein I (beta 2GPI) and human monoclonal anticardiolipin antibody (aCL) on the protein S/C4b-binding protein (C4BP) system was evaluated. The binding of C4BP to protein S was assessed by ELISA in the presence of beta 2GPI with/without human monoclonal aCL. beta 2GPI downregulated the binding between S and C4BP significantly. Human monoclonal aCL abolished the beta 2GPI inhibitory effect in a calcium (Ca++) independent fashion. In separate experiments, the reactivity of aCL towards protein S in the presence or absence of beta 2GPI and cardiolipin was investigated. Monoclonal aCL bound to protein S only in the presence of a combination of beta 2GPI and cardiolipin. This binding was Ca++ dependent. These findings suggest that human monoclonal aCL increases the affinity of C4BP for protein S, and that protein S may represent one of the targets for aCL when combined with beta 2GPI and cardiolipin. Both issues may explain acquired free protein S deficiency and the attendant risk of thrombosis in patients with aCL.

Animals↗