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PubMed2003

Increased incidence of thrombophilic abnormalities in patients with cranial dural arteriovenous fistulae.

Cranial dural arteriovenous fistulae (DAVF) may occur post-traumatic or sporadic. The physiopathologic mechanisms of sporadic DAVF are still unclear. A dural sinus thrombosis followed by an increase in venous pressure and/or an increased procoagulatory activity of the coagulation system are associated at least with some DAVF. The objective of this study was to investigate the coagulation profile in patients with DAVF. Thus the association of thrombophilic abnormalities, sinus thrombosis and DAVF should be analyzed. A total of 15 patients with cranial DAVF were included in this study. Blood samples were analyzed for 20210A mutation of the prothrombin gene, resistance to activated protein C and factor V Leiden mutation. Fibrinogen (Fib), Textarin time (TT), antithrombin (AT), protein C and protein S activity, von Willebrand factor antigen (vWF:Ag), Ristocetin cofactor activity (vWF:RCo), D-Dimer (DD) and coagulation factor VIII-activity (F VIII) were determined in all patients. Blood was screened for the occurrence of lupus antiphospholipid antibodies and cardiolipin antibodies. Thrombophilic risk factors were found in 5 (33%) of the 15 patients with cranial DAVF. Four patients had a heterozygote 20210A mutation of the prothrombin gene and one patient had a heterozygote FV Leiden mutation. Sinus thrombosis was detected in two patients with grade 2b DAVF and was associated with a 20210A mutation of the prothrombin gene in both patients. Additionally, one patient had deficient protein C activity and screening for cardiolipin antibodies was positive in three patients. In the current series the frequency of prothrombin Gene 20210A mutation was higher in patients with DAVF compared to the general population, whereas the incidence of Factor V Leiden mutation was not. Therefore in patients with cranial DAVF thrombophilic abnormalities should be considered in the post-operative/post-interventional management.

Adult↗
PubMed2004

beta2-glycoprotein I-dependent lupus anticoagulant highly correlates with thrombosis in the antiphospholipid syndrome.

The antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies in plasma of patients with thromboembolic complications. A major problem in defining the syndrome is that serologic assays to detect antiphospholipid antibodies have a low specificity. We recently published a method that specifically detects lupus anticoagulant (LAC) caused by anti-beta(2)-glycoprotein I antibodies. Here, we studied the clinical relevance of detecting beta(2)-glycoprotein I-dependent LAC. Plasma samples were collected from 198 patients with autoimmune diseases. In those samples with a positive partial thromboplastin time-lupus anticoagulant (PTT-LA), a modified activated partial thromboplastin time (aPTT)-based LAC test was performed with cardiolipin as confirming agent. Twenty-five of 58 patients with an aPTT-based LAC were dependent on the presence of anti-beta(2)-glycoprotein I antibodies. Presence of beta(2)-glycoprotein I-dependent LAC was almost completely associated with a history of thromboembolic complications (odds ratio, 42.3; 95% confidence interval, 194.3-9.9). An increased frequency of thrombosis was not found in 33 patients with LAC independent of anti-beta(2)-glycoprotein I antibodies (odds ratio, 1.6; 95% confidence interval, 3.9-0.8). The use of an LAC assay with cardiolipin as confirming agent strongly improves the detection of patients at risk of thrombosis. Our findings suggest that anti-beta(2)-glycoprotein I antibodies with LAC activity are antibodies that are responsible for the thromboembolic complications in the antiphospholipid syndrome.

Adult↗
PubMed2004

Characterisation of the Escherichia coli membrane structure and function during fedbatch cultivation.

BACKGROUND: Important parameters during recombinant protein production in Escherichia coli, such as productivity and protein activity, are affected by the growth rate. This includes the translocation of protein over the membrane to gain better folding capacity or reduced proteolysis. To vary the growth rate two techniques are available: fedbatch and continuous cultivation, both controlled by the ingoing feed rate. RESULTS: During fedbatch cultivation, E. coli contains phosphatidylethanolamine, phosphatidylglycerol, cardiolipin and saturated fatty acids in amounts which are stable with growth rate. However, the levels of cardiolipin are very high compared to continuous cultivation. The reason for fedbatch triggering of this metabolism is not known but hypothesised to result from an additional need for carbon and energy. The reason could be the dynamic and sometimes rapid changes in growth rate to which the fedbatch cell has at all times to adjust. The membrane flexibility, essential for translocation of various components, is however to some degree sustained by production of increased amounts of unsaturated fatty acids in phosphatidylglycerol. The result is a functionally stiff membrane which generally promotes low cell lysis and is constant with respect to protein leakage to the medium. At comparatively high growth rates, when the further stabilising effect of cyclic fatty acids is gone, the high level of unsaturated fatty acids results in a pronounced effect upon sonication. This is very much in contrast to the membrane function in continuous cultivation which shows very specific characteristics as a function of growth rate. CONCLUSIONS: The stiff and unchanging fedbatch membrane should promote a stable behaviour during downstream processing and is less dependent on the time of harvest. However, optimisation of protein leakage can only be achieved in the continuously cultivated cell where leakage is twice as high compared to the constant leakage level in fedbatch. If leakage is undesired, continuous cultivation is also preferred since it can be designed to lead to the lowest values detected. Induction at low growth rate (<0.2 h-1) should be avoided with respect to productivity, in any system, since the specific and total protein production shows their lowest values at this point.

Journal Article↗
PubMed2001

Immunologic and hematologic properties of antibodies to prothrombin and plasminogen in a mouse model.

Antibodies to prothrombin have been associated with venous and arterial thrombosis, and they cross-react with a structurally closely related protein plasminogen. We immunised 16 mice with human prothrombin and 15 mice with human plasminogen. Mice immunised with prothrombin developed cross-reactive antibodies to plasminogen (12/16), beta2-glycoprotein I (4/16), tissue-type plasminogen activator (6/16) and cardiolipin (11/16). Mice immunised with plasminogen developed cross-reactive antibodies to prothrombin (8/15), tissue-type plasminogen activator (2/12) and cardiolipin (5/12). Functional effects of antibodies were examined. Immunisation with prothrombin induced lupus anticoagulant activity in 9/14 mice. In mice immunised with plasminogen, radial fibrinolysis was inhibited in 8/10 and plasminogen activation in the chromogenic assay was inhibited in 9/11. No cross-functionality was observed. In conclusion, antibodies to prothrombin and plasminogen cross-react in vivo. Antibodies to prothrombin and plasminogen have different functional profiles, immunisation with prothrombin leads to prolonged blood clotting time, and immunisation with plasminogen induces antibodies interfering with fibrinolysis.

Animals↗
PubMed2005

Generation and characterization of three monoclonal IgM antiphospholipid antibodies recognizing different phospholipid antigens.

Antiphospholipid antibodies (APLs) might be involved in the pathogenesis of the antiphospholipid syndrome (APS). This study analyzes the structural characteristics of monoclonal APLs derived from patients with this disease. Patient-derived B cells were immortalized using Epstein-Barr virus transformation and subsequent fusion to the myeloma cell line CB-F7. APL-producing hybridomas were cloned to obtain cell lines producing monoclonal APL. DNA encoding the variable region of heavy and light chains of the antibodies was sequenced and analyzed regarding their usage within the V-gene family and the existence of somatic hypermutation. Binding patterns of APL to various phospholipids and beta-2-glycoprotein-I (beta2-GPI) were determined using ELISA, with special regard to beta2-GPI dependency. As a result, three APL-producing hybridoma cell lines from patients with APS were established: JGG9, HVA2, and HLC9. APLs were of the IgM isotype and showed different binding patterns toward phospholipids and beta2-GPI. One of them, JGG9, showed extensive somatic hypermutations in both the CDR3 region and a framework region of the heavy chain. JGG9 bound to cardiolipin in the presence of the protein cofactor beta2-GPI. In contrast, the antibodies HVA2 and HLC9 (which also showed somatic hypermutations in the CDR3 region) presented polyreactivity to several phospholipids-cardiolipin, phosphatidyl-serine, -ethanolamine, -inositol, -choline, and sphingomyelin-but not to beta2-GPI. In conclusion, JGG9 presents a high degree of mutation in the CDR3 and framework region resulting from the deletions of nucleotides, and affects amino acid composition. Polyreactivity and the absence of cofactor dependency present HLC9- and HVA2-like natural antibodies that have no contact with any antigen. Nonetheless, these natural antibodies show somatic hypermutation of the heavy chain, indicating antigen-driven maturation. Regarding the possible role of APL in infection, HVA2 in particular may represent a pathogen-maturated antibody showing cross-reactivity between phospholipids and infectious agents. Further experiments are needed to reveal the functional activity of these antibodies.

Amino Acid Sequence↗
PubMed1988

Effect of phospholipids on estrogen receptor of rat uterine cytosol.

Phospholipids such as phosphatidyl inositol and phosphatidyl serine inhibit the binding of R5020 and progestin receptors. The effect of phospholipids on the binding of estrogen and estrogen receptors of rat uterine cytosol was studied. Phosphatidyl choline, sphingomyelin, phosphatidyl inositol, phosphatidyl ethanolamine, cardiolipin, and phosphatidic acid inhibited the binding of estradiol and estrogen receptors. This inhibitory effect of phosphatidyl inositol and cardiolipin was dose dependent.

Animals↗
PubMed2005

The interfacial lipid binding site on the potassium channel KcsA is specific for anionic phospholipids.

Lipid binding to the potassium channel KcsA from Streptomyces lividans has been studied using quenching of the fluorescence of Trp residues by brominated phospholipids. It is shown that binding of phospholipids to nonannular lipid binding sites on KcsA, located one each at the four protein-protein interfaces in the tetrameric structure, is specific for anionic phospholipids, zwitterionic phosphatidylcholine being unable to bind at the sites. The binding constant for phosphatidylglycerol of 3.0 +/- 0.7 mol fraction(-1) means that in a membrane containing approximately 20 mol% phosphatidylglycerol, as in the Escherichia coli inner membrane, the nonannular sites will be approximately 37% occupied by phosphatidylglycerol. The binding constant for phosphatidic acid is similar to that for phosphatidylglycerol but binding constants for phosphatidylserine and cardiolipin are about double those for phosphatidylglycerol. Binding to annular sites around the circumference of the KcsA tetramer are different on the extracellular and intracellular faces of the membrane. On the extracellular face of the membrane the binding constants for anionic lipids are similar to those for phosphatidylcholine, the lack of specificity being consistent with the lack of any marked clusters of charged residues on KcsA close to the membrane on the extracellular side. In contrast, binding to annular sites on the intracellular side of the membrane shows a distinct structural specificity, with binding of phosphatidic acid and phosphatidylglycerol being stronger than binding of phosphatidylcholine, whereas binding constants for phosphatidylserine and cardiolipin are similar to that for phosphatidylcholine. It is suggested that this pattern of binding follows from the pattern of charge distribution on KcsA on the intracellular side of the membrane.

Anions↗
PubMed1996

Sneddon's syndrome (livedo racemosa and cerebral infarction) presenting psychiatric disturbance and shortening of fingers and toes.

A 24-year-old man with livedo racemosa and psychiatric disturbances, manifesting as low intelligence (IQ 80) and delusions, had anti-cardiolipin antibody and showed shortening of the fingers and toes. A skin biopsy of the livedo lesion revealed endoarteritis obliterans, being compatible with Sneddon's syndrome. MRI of the brain demonstrated multiple infarction and moderate cortical atrophy. A single photon emission tomography of the brain showed a marked reduction of the blood flow in the front-temporal lobe. These findings might relate to the psychiatric disturbance. After intravenous administration of cyclophosphamide and the start of oral prednisolone, the anti-cardiolipin antibody level decreased and his physical condition improved. However, a low dose of haloperidol is still necessary to maintain his mental condition.

Adult↗
PubMed2006

Adrenal insufficiency complicated with antiphospholipid syndrome (APS).

We describe a 69-year-old woman with bilateral adrenal hemorrhage complicated with antiphospholipid syndrome (APS). She was hospitalized with nausea and vomiting in September 2003. Laboratory data demonstrated hyponatremia, hypoglycemia and prolongation of activated partial thromboplastin time (aPTT). Abdominal computed tomography showed bilateral adrenal enlargement. In October 2003, she demonstrated altered mental status with progressive hyponatremia, a high level of ACTH, and a low level of serum cortisol. She also showed thrombocytopenia, anti-cardiolipin IgG antibody, anti-beta2GPI antibody, and lupus anticoagulants. After four months, anti-cardiolipin IgG antibody was still positive. Based on these findings, she was diagnosed as having APS complicated with adrenal insufficiency due to hemorrhagic infarction. After treatment with corticosteroid, a low dose of aspirin and normal saline infusion, her condition quickly improved. Platelet counts and aPTT were also normalized. To our knowledge, this is the second Japanese case of APS complicated with bilateral adrenal hemorrhage. APS should be considered an important underlying cause of adrenal insufficiency.

Adrenal Gland Diseases↗
PubMedDate not supplied

Evidence that the effect of soya bean phosphatidylinositol-cholesterol-cyclosporin liposomes on the biosynthesis of acidic phospholipids in isolated subcellular membranes from rat liver and heart is attributable to the soya bean phosphatidylinositol-cholesterol liposomes.

This study examined the effect of adding soya bean phosphatidylinositol-cholesterol (2:1 molar ratio) liposomes and soya bean phosphatidylinositol-cholesterol (2:1 molar ratio)-cyclosporin liposomes on the biosynthesis of [3H]polyglycerophosphatides (phosphatidylglycerolphosphate, phosphatidyl-glycerol and cardiolipin) and [3H]phosphatidylinositol in mitochondria and microsomes, respectively, isolated from rat liver and heart. The results obtained with liposomes, and liposomes containing cyclosporin, established that cyclosporin did not participate in the metabolism of acidic phospholipids. In rat liver and heart mitochondria the amount of biosynthesized [3H]polyglycerophosphatides fell to one-third and a half respectively in comparison with the amounts found when liposomes were not added. The composition of [3H]polyglycerophosphatides in both mitochondria showed an increased accumulation of [3H]phosphatidylglycerolphosphate with a concomitant decrease of about 30 per cent in [3H]phosphatidylglycerol. The biosynthesis of [3H]phosphatidylinositol in both rat liver and rat heart microsomes fell to one-third of that found in the absence of liposomes. Under similar conditions the biosynthesis of [3H]cardiolipin decreased by 50 per cent in both mitochondria. The incubation of the same liposomes and liposomes containing cyclosporin with isolated rat liver mitochondria and microsomes released about 5-7 per cent of the linoleic acid. When a corresponding amount of linoleic acid was added to the incubation mixture, the biosynthesis of [3H]polyglycerophosphatides in rat liver did not change significantly, whereas in rat heart mitochondria this biosynthesis decreased by about 33 per cent. Under these conditions, the accumulation of [3H]phosphatidylglycerolphosphate and the decrease of [3H]phosphatidylglycerol was established. The biosynthesis of [3H]phosphatidylinositol in the presence of linoleic acid in rat liver and rat heart microsomes was significantly reduced. Under similar conditions the addition of stearic acid did not significantly affect the level or composition of biosynthesized [3H]polyglycerophosphatides or biosynthesized [3H]phosphatidylinositol.

Animals↗
PubMed1992

Effects of adrenoceptor blockade on cardiac hypertrophy and myocardial phospholipids.

Catecholamines have been proposed as a stimulus for the hypertrophic response to pressure overload of the heart and could also mediate the membrane lipid changes associated with cardiac hypertrophy. To address both of these possibilities, cardiac hypertrophy was induced by aortic constriction in the presence or absence of chronic alpha- or beta-adrenoceptor blockade. Heart weights and heart weight to body weight ratios in aortic-constricted rats of the adrenoceptor-blocked and vehicle-treated groups were elevated to the same extent when compared with values in sham-operated rats of each group. Analysis of the fatty acyl composition of the major phospholipid classes revealed that similar changes occurred in vehicle-treated, alpha-blocked, and beta-blocked aortic-constricted rats when compared with respective groups of sham-operated rats. Specifically, linoleic acid was reduced in the phosphatidylcholine, phosphatidylethanolamine (PE), and cardiolipin (CL) fractions in all groups of aortic-constricted rats. This reduction was accompanied by increased docosahexaenoic acid, arachidonic acid, or palmitic acid in phosphatidylcholine; docosahexaenoic acid in phosphatidylethanolamine; and oleic acid in cardiolipin fractions. Adrenoceptor blockade did not prevent or attenuate the major changes in the fatty acyl composition of phospholipids or the increase in heart weight associated with aortic constriction. This suggests that a change in the level of adrenoceptor stimulation is not the stimulus for cardiac hypertrophy or the observed alterations in phospholipid composition in the pressure-overloaded rat heart.

Adrenergic alpha-Antagonists↗
PubMed1999

[Antiphospholipid syndrome].

Antiphospholipid Syndrome (APS) was first described by Hughes and sometimes called as Hughes syndrome. Recent studies revealed that the antigen to anticardiolipin antibody (aCL) is not cardiolipin itself but co-factor beta 2-GPI which expresses its epitope when it combines cardiolipin or gets oxidized. Lupus Anticoagulant is now possibly considered as anti-prothrombin antibody. Livedo including Snedden syndrome, pulmonary hypertension and skin ulcer became considered as the part of symptoms of this disease. In ISAPA 1998, it is reported from several laboratories that IgA aCL is also pathogenic to thrombosis as well as IgG aCL. Atherosclerosis is also accelerated by aCL. Catastrophic APS is rare but fatal, reported 3 cases in Japan and 50 cases in the world.

Antibodies, Anticardiolipin↗
PubMedDate not supplied

Valvular deposition of antiphospholipid antibodies in the antiphospholipid syndrome: a clue to the origin of the disease.

In this report we present an unusual case of a 45-year-old female patient with systemic lupus erythematosus (SLE) who was hospitalized for mitral valve replacement. In her childhood she presented with mitral stenosis and chorea on which grounds a preliminary diagnosis of rheumatic fever was established. After a quiescent period lasting two decades her disease erupted with mitral stenosis, thromboembolic phenomena, and nephritis. Due to severe malfunctioning of her mitral valve, the patient eventually underwent mitral valve replacement. The antibodies involved in the pathogenesis of our patient's valvular disease were studied by immunohistochemical analysis, applying rabbit polyclonal anti-human IgG and IgM anti-human C3c and anti-idiotypes to a mouse monoclonal naturally occurring polyspecific human monoclonal anti-cardiolipin antibody termed S2.9, and to the 16/6 Id which defines a common Id on anti-DNA antibodies in patients with SLE. Immunoperoxidase staining using an anti-idiotype mAb to anti-cardiolipin antibodies demonstrated the deposition of these anti-bodies in the subendothelial layer of the valve. We believe that anti-phospholipid syndrome (APS) with SLE was the initial and primary disease in this patient. These findings clearly indicate that APS must be considered in the differential diagnosis of rheumatic fever, particularly in young female patients who present with mitral stenosis and chorea.

Adolescent↗
PubMed1999

The effect of the duration of anticoagulation and other risk factors on the recurrence of venous thromboembolisms. Duration of Anticoagulation Study Group.

BACKGROUND: In order to find the optimal balance of anticoagulation, avoiding recurrent events as well as major hemorrhage, it is important to know the impact of different risk factors over time. METHODS: Based on a randomized, multicenter trial on different durations of anticoagulation after a first episode of venous thromboembolism, the probability of recurrence over 6 years of follow-up was analyzed. The contribution of the site of the thrombus, the nature of the triggering risk factor and the presence of cardiolipin antibodies to the risk of recurrence was also calculated. RESULTS: There is a cumulative risk of recurrence of 4 to 5% per year, which continues through year 6 after the index event, independent of the initial duration of anticoagulation. Deep vein thrombosis proximal to the knee joint or symptomatic pulmonary embolism confers a risk of recurrence that is higher than of distal thrombosis but equal to the risk when the triggering factor is permanent or unknown. The combination of proximal deep vein thrombosis or symptomatic pulmonary embolism and permanent/unknown triggering factor increases the risk, and the presence of cardiolipin antibodies generates an additional risk in all subgroups. CONCLUSION: It is necessary to tailor the duration of anticoagulation individually, according to the presence of different risk factors.

Antibodies, Anticardiolipin↗
PubMed1999

[Antibodies to various phospholipids in SLE patients with primary antiphospholipid syndrome].

Antiphospholipid antibodies (aPL) represent a heterogeneous population reacting with negatively charged, less frequently neutral phospholipids and/or phospholipid-binding serum proteins. The study was made of antibodies to a wide spectrum of phospholipids: to negatively charged phospholipids such as phosphatide acid (aPA), cardiolipin (aCL), phosphatidylcholine (aPS), phosphatidylinositol (aPI), phosphatidylglycerol (aPG) and to neutrally charged phospholipid--phosphatidylcholine (aPC)--in 54 patients with systemic lupus erythematosus (SLE) and 29 patients with primary antiphospholipid syndrome (PAPS). The test for lupus anticoagulant (LAC) was also made. aPL in SLE patients free of antiphospholipid syndrome were detected in 61, 36 and 9% (aPC, aPS and aPA, aCL, respectively). aPI and aPG did not exceed normal values. 81% of SLE patients with antiphospholipid syndrome were LAC positive and 88% aPL positive. 60, 53, 44, 40, 13 and 17 were positive to aPC, aPA, aPS, aCL, aPG and aPI, respectively. Among patients with PAPS, the highest positivity was by LAC, occurrence of the other aPL was the same as in SLE patients with antiphospholipid syndrome. aCL, aPA, aPC, aPS, aPG and aPI were found in 55, 52, 41, 38, 31 and 21% of cases, respectively. In clinical manifestations of antiphospholipid syndrome and negative tests for LAC and aCL it is advisable to make tests for aPS and aPC. aPC occur in SLE patients more frequently than the other aPL: in 63% of SLE patients free of antiphospholipid syndrome and in 60% of SLE patients with this syndrome. Antibodies to other phospholipids, but not to cardiolipin, were present in SLE + APS in half of the cases but in SLE + PAPS in one third of the patients. Occurrence of aCL in the serum of SLE + PAPS patients is associated with the presence of antibodies to any other phospholipid irrespective of the charge. The severity of vascular changes did not correlate with the number of aPL variant found in the serum.

Adolescent↗
PubMed1999

Inhibition of trophoblast adhesion to endothelial cells by the sera of women with recurrent spontaneous abortions.

PROBLEM: May anti-phospholipid or other autoantibodies interfere with trophoblast-endothelial cells interaction in women with unexplained pregnancy losses? METHODS OF STUDY: The sera of 72 women with recurrent spontaneous abortions (RSA) containing antibodies to endothelial cells (28), trophoblast (14), and cardiolipin (10) or lacking antibodies (25), and 26 controls were examined in an inhibition assay of trophoblast adhesion to endothelial cells using an ELISA based on the recognition of trophoblast by antibodies to cytokeratin. RESULTS: Adhesion of trophoblast to endothelial cells was time- and dose-dependent. Patients and control sera inhibited trophoblast adhesion with mean values of 37% and 7%, respectively. Inhibition above 2SD of the mean control value was still observed in 58% of the patients sera and 8% of the control sera. Sera containing antibodies to endothelial cells had higher inhibitory effect (38%) than those with antibodies to trophoblast (23%) and cardiolipin (28%) or lacking antibodies (26%). CONCLUSIONS: Antibodies and other undefined factors in the sera of women with RSA inhibit adhesion of trophoblast to endothelial cells.

Abortion, Habitual↗
PubMed1999

Screening for a prothrombotic diathesis in patients attending family planning clinics.

AIMS: 1. To determine the frequency of prothrombotic markers in young women seeking a new or a repeat prescription of the oral contraceptive pill and perceived to be at high risk of thrombosis. 2. To assess cost-effectiveness of thrombophilia testing within this population. 3. To determine the frequency of acquired activated protein C (APC) resistance. METHODS: Results of thrombophilia testing were retrospectively reviewed on 220 consecutively referred patients' plasmas. Women tested were clients attending local family planning clinics for a new or repeat contraceptive prescription. Samples for testing were collected by the Community Laboratory Service. Investigations included: antithrombin III (AT III), protein C, protein S, APC resistance, factor V Leiden mutation analysis and anti-cardiolipin antibodies. RESULTS: Abnormalities were detected in 35 (15.9%) of the 220 women tested. No patient had all tests performed. The most frequently detected abnormality was an increased APC resistance in 6.8% of the women tested. Three of the 13 patients with an abnormal APC resistance had a discrepancy between the low APC ratio and a negative mutation analysis result for factor V Leiden, suggesting acquired APC resistance. Deficiency of protein C was found in 1.2% (of 162), protein S in 2.0% (of 140), antithrombin III in 0.6% (of 159). Low-titre anti-cardiolipin antibodies were detected in 13.9% of this group (115 tested). CONCLUSIONS: The frequency of abnormal thrombophilia markers detected in this cohort of young women is not significantly different from that seen in a control population. This low incidence suggests that testing has been applied on a population screening basis, rather than preselecting a high-risk group. Thrombophilia screening in this patient group cannot be justified when the clinically relevant end-point is death from pulmonary embolism. The cost of preventing one fatal pulmonary embolism arising as a consequence of screening for activated protein C resistance due to the commonly occurring factor V Leiden is a minimum $25,000,000. This compares very unfavourably with the estimated cost per life saved in the National Breast Screening Programme.

Activated Protein C Resistance↗
PubMedDate not supplied

[Detection of antibodies to beta-amyloid in carriers of E280A mutation in the presenilin-1 gene].

OBJECTIVE: To investigate some immune component that could contribute to the pathogenesis of Alzheimer's disease associated with the E280A mutation of the presenilin-1 gene (PS-1). PATIENTS AND METHODS: Serum antibodies against both cardiolipin and beta-amyloid peptides (beta 1-40 and beta 1-42) were quantitated by means of an indirect ELISA technique in carriers of the mutation, either healthy or with Alzheimer's disease, as well as in normal controls without the mutation. RESULTS: Out of 19 patients with Alzheimer's disease only 2 had increased values of antibodies to cardiolipin, namely: one with 14.58 micrograms/ml of IgM and the other with 36.16 micrograms/ml of IgG. The remaining individuals revealed values under 10 micrograms/ml, considered normal, and there was no significant difference between the groups. Significant serum reactivity (p < 0.001) was detected against both beta-amyloid peptides in the mutation carriers, either with or without Alzheimer's disease, as compared to the control group. No correlation was detected between this antibody response and the mental or functional situation of the patients. CONCLUSION: beta-amyloid antibodies, present in the mutation carriers, may simply represent a marker of immune activation induced by beta-amyloid with no in vivo effect; however, despite the results, the possibility can not be ruled out of a pathogenic role of these antibodies in early onset Alzheimer's disease.

Adult↗

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