bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolactin Levels Are Associated with Lupus Activity, Lupus Anticoagulant, and Poor Outcome in Pregnancy
Authors: JARA LUIS J. , PACHECO‐REYES HEIDI , MEDINA GABRIELA , ANGELES ULISES , CRUZ‐CRUZ POLITA , SAAVEDRA MIGUEL A.
Published: October 2007

Abstract:  High prolactin (PRL) levels seem to be associated with active systemic lupus erythematosus (SLE) during pregnancy. However, the association of activity, lupus anticoagulant (LA), and pregnancy outcome has not been analyzed. The objective of this study was to analyze the association among SLE activity, LA, and maternal–fetal outcome. We studied 15 pregnant SLE patients (ACR criteria), 4 of them with associated antiphospholipid syndrome (APS), and 9 healthy pregnant women. All patients were evaluated monthly with the following determinations: (a) SLE activity using modified‐systemic lupus activity measurement (m‐SLAM), (b) LA, and (c) PRL serum levels. Healthy controls were evaluated each trimester. Prematurity, fetal loss, low birth weight, and preeclampsia were evaluated. Chi‐square test, Fisher's exact test, Student's t‐test, Pearson correlation, and ANOVA were performed. The mean age of SLE patients was 30 ± 4.9 years and 27.1 ± 3.7 years in controls. High PRL levels were found during the second and third trimester in SLE patients in comparison with controls (186.2 ± 54.02 ng/mL versus 119.6 ± 31.1 ng/mL (P < 0.01) and 177.4 ± 48.6 ng/mL versus 158.3 ± 31.5 ng/mL. A significant linear correlation between PRL, m‐SLAM, and LA in association with poor maternal–fetal outcome was observed. LA and PRL conferred risk for poor pregnancy outcome. Our study indicates for the first time a strong association among PRL, LA, SLE activity, and poor pregnancy outcome. Close rheumatologic and obstetric monitoring is mandatory in SLE pregnancy in order to avoid obstetric complications.
Unstabilized DNA Breaks in Lymphocytes of Patients with Different Subsets of Systemic Sclerosis
Authors: MAJONE FRANCA , COZZI FRANCO , TONELLO MARTA , OLIVIERI SILVIA , MONTALDI ANNA , FAVARO MARIA , VISENTIN SERENA , LUISETTO ROBERTO , RUFFATTI AMELIA
Published: October 2007

Abstract:  The clastogenic effects on DNA, proven by the presence of micronuclei (MN) and the protective cellular mechanisms normally used to stabilize DNA breaks were investigated in three subsets of patients with systemic sclerosis (SSc). The frequency of MN found in cultures of peripheral lymphocytes in patients with anticentromere and antitopoisomerase I antibodies was significantly higher than that in the control group. The group with anticentromere antibody showed a significantly higher frequency of MN than did the subjects with antitopoisomerase antibody (4.22% versus 2.34%, P < 0.001). Patients with anti‐RNA polymerase III, instead, had a low prevalence of typical micronucleated cells (0.98%), not significantly different from that of the healthy controls (0.82%). Moreover, when MN was characterized for the presence or absence of DNA fragments with free 3′‐OH ends by digoxigenin‐dUTP (DIG‐dUTP) using terminal deoxynucleotidil transferase, its frequency was found to be increased in the groups with anticentromere and antitopoisomerase I antibodies with respect to that in the controls. The increase was significantly higher in the lymphocytes of the patients with anticentromere than in those with antitopoisomerase I antibody (35% versus 20.08%, P < 0.001). Nonetheless, the prevalence of unstable DNA fragments in patients with anti‐RNA polymerase III antibody was low (2.05%) and not significantly different from that of the control group (1.18%). Our results indicate that there is a clastogenic effect on DNA and an interference in the protective cellular mechanisms normally stabilizing DNA breaks only in some subsets of SSc patients.
Early Atherosclerosis and Autoantibodies to Heat‐Shock Proteins and Oxidized LDL in Systemic Sclerosis
Authors: SHERER YANIV , CERINIC MARCO MATUCCI , BARTOLI FRANCESCA , BLAGOJEVIC JELENA , CONFORTI MARIA LETIZIA , GILBURD BORIS , EHRENFELD MICHAEL , SHOENFELD YEHUDA
Published: October 2007

Abstract:  Autoimmune diseases are characterized by enhanced atherosclerosis. Humoral immune responses to mycobacterial HSP‐65, human HSP‐60, and to oxLDL have been established in a number of human autoimmune diseases and are considered to be associated with atherosclerosis. The aim of this study was to evaluate carotid artery intima‐media thickness (IMT) in patients having systemic sclerosis (SSc) and to find out whether early atherosclerosis is associated with these autoantibodies. Forty‐four patients having SSc underwent clinical evaluation and carotid artery IMT measurement. Several autoantibodies were tested among patients and a control group. The antibodies against human HSP‐60 were measured by antihuman (IgG/IgM) HSP‐60 ELISA kit. IgGs and IgMs antimycobacterial HSP‐65 were determined using an ELISA with mycobacterial recombinant HSP‐65 antigens. Similarly, anti‐oxLDL antibodies were measured by an ELISA kit. Abnormal IMT levels were significantly more common in SSc patients compared with control subjects. Age was found as the sole most significant clinical parameter associated with carotid artery IMT in SSc. Disease duration, type of SSc, lung function tests, and cardiovascular risk factors were not associated with IMT in these patients. Levels of HSP‐60, HSP‐65, and oxLDL autoantibodies were similar among patients compared with controls, and in patients having “positive” IgM anti‐HSP‐65, higher IMT values were found. Abnormal carotid IMT is more prevalent in SSc than in normal subjects. Age rather than other clinical parameters is associated with early atherosclerotic changes in SSc. Autoantibodies to oxLDL, HSP‐60, and HSP‐65 are not elevated in SSc and there is only a borderline association with carotid artery IMT.
Systemic Sclerosis‐Associated Myopathy
Authors: RANQUE BRIGITTE , AUTHIER FRANÇOIS‐JÉRÔME , BEREZNE ALICE , GUILLEVIN LOÏC , MOUTHON LUC
Published: October 2007

Abstract:  Skeletal muscle involvement is a common feature in systemic sclerosis (SSc) because muscle weakness is found in up to 90% SSc patients when systematically assessed. Muscle clinical, biological, and electromyographic features are similar to those of polymyositis or dermatomyositis, except for a higher proportion of mild symptoms. SSc‐associated myopathy is more prevalent in diffuse SSc and is also associated with cardiomyopathy. The pathophysiological process leading to SSc‐associated myopathy is likely to be complex, given the heterogeneity of pathological muscle findings, including stigma of microangiopathy, and also inflammatory infiltrate in about half of the cases and interstitial fibrosis. Conflicting results have been reported regarding the correlation between clinicobiological presentation and pathological muscle features, nevertheless there is a general agreement that histologically proven inflammatory myopathies usually regress under high‐dose corticosteroid therapy, or even low dose in case of positive anti‐PM/Scl antibody. In contrast, noninflammatory myopathies often result in milder clinical expression but do not respond to immunosuppressive treatment.
Citrullination by Peptidylarginine Deiminase in Rheumatoid Arthritis
Authors: SUZUKI AKARI , YAMADA RYO , YAMAMOTO KAZUHIKO
Published: October 2007

Abstract:  Rheumatoid arthritis (RA) is a complex, multifactorial disease with genetic and immunological aspects. Because RA is an autoimmune condition, dysregulation of the immune system is implied. Many linkage and association studies have also indicated that multiple genetic factors are associated with RA. Although the contribution of each genetic factor is small, the combination of these factors affects RA development. Previous studies have suggested that genetic changes affect the internal immunological environment, which results in autoimmune diseases. More recent genetic studies indicate that the HLA‐DRB gene is the predominant cause of RA and that other non‐HLA genes are also involved. We reported that peptidylarginine deiminase (gene name abbreviated to PADI, protein name abbreviated to PAD) type 4 is the one of the non‐HLA genetic factors involved in RA via citrullination. Antibodies against citrullinated proteins/peptides are highly specific to RA, but the physiological roles of PADI gene, PAD proteins as their products and citrullinated proteins/peptides are obscure. However, levels of anticitrullinated protein antibodies are apparently also increased and were involved in the pathogenesis of autoimmune arthritis in mice with collagen‐induced arthritis (CIA). These data suggested that citrullinated protein and anticitrullinated protein antibodies play important roles in the development of RA. This review summarizes the relationship between RA and citrullination, as well as the role of PADI4 genetics.
Regulation of Cytokine‐Induced HIF‐1α Expression in Rheumatoid Synovial Fibroblasts
Authors: WESTRA JOHANNA , BROUWER ELISABETH , BOS REINHARD , POSTHUMUS MARCEL D. , DOORNBOS‐VAN DER MEER BERBER , KALLENBERG CEES G.M. , LIMBURG PIETER C.
Published: October 2007

Abstract:  The transcription factor hypoxia‐inducible factor (HIF)‐1 plays a central physiological role in oxygen and energy homeostasis, and is activated during hypoxia by stabilization of the subunit HIF‐1α. Activation can also occur by proinflammatory cytokines during inflammation. Hypoxia, as well as proinflammatory cytokines, plays an important role in the synovia in rheumatoid arthritis (RA) patients. Expression of HIF‐1α has been demonstrated in RA synovial lining layer. The aim of the study was to investigate the regulation of the intracellular signal transduction pathways, involved in the expression of HIF‐1α, and in the expression of genes regulated by HIF‐1α in rheumatoid synovial fibroblasts (RSF). RSF were cultured under proinflammatory conditions (IL‐1β and TNF‐α stimulation) and under chemical hypoxia (CoCl2 treatment). Expression of HIF‐1α was analyzed in nuclear extracts by Western blotting. The effect of inhibitors of the PI3K and the ERK pathway on HIF‐1α protein expression was measured. mRNA expression of HIF‐1α, COX‐2, vascular endothelial growth factor (VEGF), and stromal cell‐derived factor (SDF)‐1 was determined by real‐time RT‐PCR, and protein production of VEGF and SDF‐1 by ELISA. Treatment of the synovial fibroblasts with 150 mM CoCl2 as well as stimulation with 10 ng/mL IL‐1β or TNF‐α resulted in strong protein expression of HIF‐1α, measured with Western blotting. Pretreatment with the MEK1/2 inhibitor PD98059 as well as the PI3K inhibitor LY294002 resulted in inhibition of the cytokine‐induced HIF‐1α expression. Furthermore, it was shown that cytokine‐induced mRNA expression of HIF‐1α was inhibited by the PI3K inhibitor. We found that cytokine stimulation induced VEGF mRNA and protein production, but no significant effect of kinase inhibition was found on VEGF production in cytokine‐stimulated RSF. Both the ERK pathway and the PI3K pathway are involved in the cytokine‐induced HIF‐1α expression in RSF and in the expression of proangiogenic factors.
A New Target for Autoantibodies in Patients with Rheumatoid Arthritis
Authors: ROBERT‐PACHOT MAGALI , DESBOS AGNES , MOREIRA ANNICK , BECCHI MICHEL , TEBIB JACQUES , BONNIN MICHEL , AITSISELMI TARIK , BIENVENU JACQUES , FABIEN NICOLE
Published: October 2007

Abstract: Early treatment of rheumatoid arthritis (RA) with disease‐modifying antirheumatic drugs can achieve a better disease outcome and reduce the severity of joint damage. The presence of autoantibodies in patient sera can precede onset of the disease and thus be predictive of the development of RA. To date, known autoantibodies in RA are positive in only 50–60% of RA patients at onset of disease and even less before the onset of any RA symptom. The aim of this study was to identify new antibodies that could be useful for the diagnosis of RA using synovial membrane proteins, which represent the best source of candidate RA autoantigens. The humoral reactivity of sera from RA patients was explored using immunoblotting on extracted proteins obtained from synovial membranes from RA after synovectomy or arthroplasty. A new target protein with a molecular weight of 26 kDa was found to be recognized by autoantibodies in RA sera. This protein was identified using MALDI‐TOF mass spectrometry and two‐dimensional electrophoresis as carbonic anhydrase III with a high level of confidence. In conclusion, this study demonstrates new autoantibodies in RA patients that are directed against carbonic anhydrase III. The sensitivity and specificity of these new autoantibodies for RA have to be further evaluated.
Heat‐Shock Protein 65 Autoantibodies Are Differently Associated with Early Atherosclerosis in Rheumatoid Arthritis and in Healthy Subjects
Authors: SHERER YANIV , GERLI ROBERTO , BOCCI ELENA BARTOLONI , GILBURD BORIS , VAUDO GAETANO , BISTONI ONELIA , SHOENFELD YEHUDA
Published: October 2007

Abstract:  The aim of this study was to examine whether heat‐shock protein (HSP)‐65 autoantibodies are associated with early atherosclerosis in rheumatoid arthritis (RA). Intima‐media thickness (IMT) was measured in the carotid arteries of 100 RA patients and 69 control subjects. The IMT was evaluated on both carotid arteries in the common carotid, bifurcation, and internal arteries. Every patient underwent anti‐HSP‐65 antibody evaluation. Anti‐HSP‐65 antibodies were not more prevalent among patients compared with controls. Among controls, patients having “positive” anti‐HSP‐65 tended to have increased carotid artery IMT compared with “negative” patients, whereas among RA patients the opposite association was noted, and positive patients had significantly decreased carotid bifurcation IMT than negative patients without elevated levels of anti‐HSP‐65. As opposed to the association with cardiovascular diseases and atherosclerosis of anti‐HSPs in the general population, among RA patients anti‐HSP‐65 cannot be regarded as associated with early atherosclerosis.
Antibodies against Alpha‐Fodrin Are Associated with Sicca Syndrome in the General Population
Authors: WITTE TORSTEN , MATTHIAS TORSTEN , BIERWIRTH JANINE , SCHMIDT REINHOLD E.
Published: October 2007

Abstract:  The significance of antibodies against alpha‐fodrin compared to antibodies against Ro (SSA) as markers of Sjögren's syndrome has been controversially discussed. We therefore compared the association of alpha‐fodrin and Ro antibodies with dry eyes and dry mouth in the general population. In 168 “normal” participants, the prevalence of IgA antibodies against alpha‐fodrin was 5% and of IgG antibodies against alpha‐fodrin was 3%. IgA antibodies against alpha‐fodrin were present in 3 of 4 and IgG antibodies against alpha‐fodrin in 2 of 4 participants with the combination of dry eyes and dry mouth (P= 0.0002 and 0.005). Only one participant had antibodies against Ro and had dry eyes but normal saliva production. Antibodies against alpha‐fodrin are associated with sicca syndrome and may be valuable diagnostic markers in patients with Sjögren's syndrome lacking Ro antibodies.
Sjögren's Syndrome—A Plethora of Clinical and Immunological Phenotypes with a Complex Genetic Background
Authors: JONSSON ROLAND , BOLSTAD ANNE ISINE , BROKSTAD KARL A. , BRUN JOHAN G.
Published: October 2007

Abstract:  Primary Sjögren's syndrome is a complex autoimmune disorder, considered to represent an ideal disease with which to study the mechanisms underlying autoimmunity because its manifestations are both organ specific and systemic in nature. The characteristic histologic finding in target organs is a progressive focal infiltration of mononuclear lymphoid cells, replacing glandular epithelium (lymphoepithelial lesion). This involvement has been re‐emphasized in the 2002 revised EU criteria for Sjögren's syndrome. Moreover, ectopic secondary lymphoid follicles in Sjögren's syndrome contain all elements of relevance for driving an autoimmune response. A number of cytokines and chemokines are involved and particularly B cell activating factor seems to direct the lifespan of infiltrating B cells by enhancing their proliferation and maturation. The recent discovery of clinical benefit after B cell depletion also highlights the pivotal role of B cells in Sjögren's syndrome. A major challenge in Sjögren's syndrome will be to stratify the disease process including genetic and environmental triggers. Identification of novel genetic and molecular markers may lead to the development of better diagnostic and prognostic tools in Sjögren's syndrome including its systemic complications. This minor review will cover the current knowledge on classification, pathogenesis, multiplex findings, potential candidate genes, gene profiling results, and novel therapy approaches. New hypotheses behind the complexity of Sjögren's syndrome are expected to follow.
Catastrophic Antiphospholipid Syndrome
Authors: CERVERA RICARD , BUCCIARELLI SILVIA , ESPINOSA GERARD , GÓMEZ‐PUERTA JOSÉ A. , RAMOS‐CASALS MANUEL , SHOENFELD YEHUDA , PIETTE JEAN‐CHARLES , ASHERSON RONALD A.
Published: October 2007

Abstract:  Although less than 1% of patients with the antiphospholipid syndrome (APS) develop the catastrophic variant, its potentially lethal outcome emphasizes its importance in clinical medicine today. However, the rarity of this variant makes it extraordinarily difficult to study in any systematic way. In order to put together all the published case reports as well as the new diagnosed cases from all over the world, an international registry of patients with catastrophic APS (“CAPS Registry”) was created in 2000 by the European Forum on Antiphospholipid Antibodies. Currently, it documents the entire clinical, laboratory, and therapeutic data of more than 300 patients whose data have been fully registered. This registry can be freely consulted at the Internet (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM) and it is expected that the periodical analysis of these data will allow us to increase our knowledge of this condition.
Antigenic Profile, Prevalence, and Clinical Significance of Antiphospholipid Antibodies in Women Referred for in Vitro Fertilization
Authors: SANMARCO M. , BARDIN N. , CAMOIN L. , BEZIANE A. , DIGNAT‐GEORGE F. , GAMERRE M. , PORCU G.
Published: October 2007

Abstract:  The aim of this prospective study was to assess the prevalence of antiphospholipid antibodies (aPL) in women who had undergone in vitro fertilization (IVF) and the relationship between aPL and IVF outcome. A total of 101 infertile women with at least three unsuccessful IVF attempts were consecutively included in this study. Samples were collected in the follicular phase of a spontaneous ovarian cycle 2 months after the last ovulation induction treatment. Age‐matched healthy fertile women (n= 160) were included as controls. All were evaluated for the presence of lupus anticoagulant (LA), antibodies (IgG, IgA, IgM) to cardiolipin (aCL), beta2‐glycoprotein I (aβ2GPI), and phosphatidylethanolamine (aPE). Out of the 101 infertile women, 40 were persistently positive for aPL, showing a prevalence significantly higher than in controls (39.6% versus 5%, P < 0.0001). Among aPL, aPE were found with a significantly higher prevalence compared with LA, aCL, and aβ2GPI (67.5% versus 0%, 15%, and 40%, respectively). Interestingly, aPE were found in 70% of the cases in the absence of the other aPL. The predominant isotype of aPL was IgA, in particular for aβ2GPI. Finally, no significant association was found between the presence of aPL and IVF outcome. This prospective study shows aPE as the most prevalent aPL in infertile women and IgA as more common than IgG and IgM. However, our results do not support an association between aPL and IVF outcome.
Antiphospholipid Antibodies in Patients with Coronary Artery Disease
Authors: GRECO TOM P. , CONTI‐KELLY ANN MARIE , MATSUURA EIJI , GRECO TOM , DIER KEN J. , SVANAS GREGORY , DOYLE ROBIN , LOPEZ LUIS R.
Published: October 2007

Abstract:  Antiphospholipid antibodies (aPL) have been implicated in the pathogenesis of coronary artery disease (CAD). We evaluated the presence of aPL in patients with chest pain/acute coronary syndromes (ACS) to determine if aPL were associated with the presence and severity of CAD, adverse outcomes, and other coronary risk factors. Patients with chest pain/ACS were evaluated for aPL prior to diagnostic and therapeutic investigations. Coronary angiograms were graded according to the severity of disease. Risk factors, including family histories, were assessed and patients were followed for adverse outcomes. To date, 232 patients (116 M, 116 F, mean age 63 years) with a mean follow‐up of 9 months were studied. Thirty‐seven percent (86/232) were positive for one or more aPL. More women, 49/86 (57%), were aPL positive versus men, 37/86 (43%). The presence of aPL appeared associated with both presence and severity of CAD (P= 0.176 women; P= 0.163 men). In patients undergoing procedures (angioplasty, stent, bypass), aPL was significantly associated with both an increase in adverse cardiac outcomes (P= 0.045) and extracardiac thrombotic events (P= 0.033). Anti‐β2 glycoprotein‐1 (aβ2GP1) was the most frequent aPL, occurring in 68.5% of aPL‐positive patients with CAD. Anticardiolipin antibody (aCL) occurred in only 7.4%. IgM isotypes were the most frequent for all categories of aPL (range 55–90%). Family history of antiphospholipid syndrome (APS)‐related events was more significant in aPL‐positive than aPL‐negative individuals (P= 0.027).
Subclinical Atherosclerosis in Primary Antiphospholipid Syndrome
Authors: MARGARITA ANNAMARIA , BATUCA JOANA , SCENNA GIOVANNA , ALVES JOSE' DELGADO , LOPEZ LOUIS , IANNACCONE LUIGI , MATSUURA EIJI , AMES PAUL R.J.
Published: October 2007

Abstract:  To test the atherosclerosis hypothesis in primary antiphospholipid syndrome (PAPS) we measured intima media thickness (IMT) of carotid arteries and other cardiovascular risk factors in 44 patients with PAPS (mean age 35 ± 12 years), in 25 patients with inherited thrombophilia (mean age 40 ± 10 years), and in 34 normal controls (mean age 38 ± 11 years). The frequency of smoking, hypertension, and dyslipidemia was similar across groups. IMT was almost similar across groups at age groups below 40 years but IMT was greater in PAPS than controls at the common carotid (P= 0.01), at the bifurcation (P= 0.003), and at the internal carotid (P= 0.005) in the age group over 40 years. Atherosclerosis is a possibility in PAPS patients in their fourth decade of life or older.
Atherogenic Antiphospholipid Antibodies in Antiphospholipid Syndrome
Authors: KOBAYASHI KAZUKO , LOPEZ LUIS R , MATSUURA EIJI
Published: October 2007

Abstract:  Macrophage uptake of oxidized LDL (oxLDL) plays a critical role in early stages of atherosclerosis. We previously reported that oxLDL forms stable complexes with β2‐glycoprotein I (β2GPI), and that these complexes were frequently present in the sera of patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). oxLDL/β2GPI complexes were shown to be antigenic targets for autoantibodies present in APS. To understand the role of autoantibodies in accelerated atherosclerosis of SLE and APS, we investigated the binding characteristics of β2GPI and oxLDL to mouse macrophages, and the effect of anti‐β2GPI and anti‐oxLDL autoantibodies on this macrophage binding. IgM anti‐oxLDL antibody (derived from Apoe−/– mouse) showed inhibitory effect on oxLDL binding to macrophages. Although β2GPI partly inhibited oxLDL binding to macrophages, IgG anti‐β2GPI autoantibody (derived from APS model mouse) showed pro‐atherogenic property by promoting the binding of oxLDL/β2GPI to macrophages.
A Novel Overlap Syndrome
Authors: ZANDMAN‐GODDARD GISELE , TWEEZER‐ZAKS NURIT , SHALEV TAMAR , LEVY YAIR , EHRENFELD MICHAEL , LANGEVITZ PNINA
Published: October 2007

Abstract:  Antiphospholipid syndrome (APS) can be either primary or secondary to autoimmune diseases, malignancies, infectious diseases, or drug‐induced conditions. The aim of this study was to describe a novel overlap syndrome of APS and systemic sclerosis (SSc) in a case series. A retrospective review of medical files of hospitalized patients who were followed in two rheumatology clinics in Israel for the diagnosis of SSc and APS was sought. A MEDLINE search was performed for reports of APS/SSc overlap syndrome. Five patients with the overlap syndrome of APS and SSc were retrieved. The diagnosis of both diseases was confirmed by the American College of Rheumatology classification criteria. Four patients were women and of an older age group (42–68 years old). Three patients had primary APS, and in two patients APS was secondary to SSc. Two of the five patients died. The interval between APS and SSc was <1–18 years. APS/SSc overlap syndrome is described for the first time as a case series. The patients may be older, with an interval of up to 18 years between diseases. The APS patients did not suffer from SLE. The overlap syndrome was characterized in certain instances with severe disease and two patients died. With relevant clinical manifestations, APS should be sought in SSc patients and treated appropriately.
Peripheral Vascular Occlusions Leading to Gangrene and Amputations in Antiphospholipid Antibody Positive Patients
Authors: ASHERSON RONALD A. , CERVERA RICARD , SHOENFELD YEHUDA
Published: October 2007

Abstract:  Twenty‐one cases from several medical centers (Brazil, Italy, Serbia, South Africa, Israel, and the United Kingdom) with severe peripheral vascular disease progressing to amputations of limbs/digits, all of whom tested positive for antiphospholipid antibodies, are documented. The patients were suffering from either systemic lupus erythematosus, discoid LE, “primary” antiphospholipid syndrome (PAPS), “lupus‐like” disease, undifferentiated connective tissue disease. A high frequency of livedo reticularis preceding the arterial occlusions in our series of patients who subsequently progressed to ischemic necrosis and amputation of limbs/digits was noted. Five of the 10 patients, in whom histopathological studies had been performed, demonstrated the typical vasculopathy seen with the antiphospholipid syndrome (“APS vasculopathy”). Complicating vasculitis was present in seven of the patients. Five of the patients developed severe peripheral vascular disease during the course of the catastrophic antiphospholipid (Asherson's) syndrome.
Uterine Artery Velocity Waveforms as Predictors of Pregnancy Outcome in Patients with Antiphospholipid Syndrome
Authors: DE CAROLIS SARA , BOTTA ANGELA , GAROFALO SERAFINA , FERRAZZANI SERGIO , MARTINO CARMELINDA , FATIGANTE GABRIELLA , CAFORIO LEONARDO , CARUSO ALESSANDRO
Published: October 2007

Abstract:  In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk for preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation, as the likely consequence of the physiologic change of spiral arteries into low‐resistance vessels. The presence of antiphospholipid antibodies can impair this vascular adaptation, resulting in a reduced placental perfusion. Doppler investigation provides a noninvasive method for the study of uteroplacental blood flow. Several studies were performed to detect the predictive role of uterine artery Doppler velocimetry in relation to pregnancy outcome in APS patients. In some studies, a high resistance index in the uterine arteries strongly predicted the subsequent development of obstetric complications. In other studies, persistent bilateral uterine artery notches identified the risk of preeclampsia and fetal intrauterine growth restriction. To date, the uterine artery Doppler velocimetry resulted to be a useful tool for identifying APS pregnancies at risk for adverse pregnancy outcome. These findings might have important implications for the management of these patients.
In Vivo Effects of an Inhibitor of Nuclear Factor‐Kappa B on Thrombogenic Properties of Antiphospholipid Antibodies
Authors: MONTIEL‐MANZANO G. , ROMAY‐PENABAD Z. , PAPALARDO DE MARTÍNEZ E. , MEILLON‐GARCÍA L. A. , GARCÍA‐LATORRE E. , REYES‐MALDONADO E. , PIERANGELI S. S.
Published: October 2007

Abstract:  It has been shown that endothelial cell (EC) activation and tissue factor (TF) upregulation in EC and monocytes by antiphospholipid antibodies (aPL Abs) leads to a prothrombotic state and involves translocation of nuclear factor‐kappa B (NF‐κB). Here we examined the effects of an NF‐κB inhibitor on aPL‐induced thrombosis, TF activity, and EC in vivo. We treated CD1 mice with IgG from a patient with antiphospholipid syndrome (IgG‐APS) or with control IgG (IgG‐NHS). The adhesion of leukocytes (number of white blood cells) to EC in cremaster muscle (as an indication of EC activation) as well as the size of an induced thrombus in the femoral vein of the mice were examined. Some mice in each group were infused with 10 μM MG132 (an inhibitor of NF‐κB). TF activity was determined using a chromogenic assay in homogenates of carotid arteries and in peritoneal cells of mice. In vivo, IgG‐APS increased significantly the number of white blood cells adhering to ECs (4.7 ± 2.2) when compared to control mice (1.5 ± 0.8), and these effects were significantly reduced when mice were pretreated with MG132 (0.8 ± 0.2). IgG‐APS increased significantly the thrombus size and MG132 inhibited that effect (93%). Treatment of the mice with IgG‐APS also induced significantly increased TF function in peritoneal cells and in homogenates of carotid arteries. Pretreatment of the mice with MG132 abrogated those effects significantly. Mice injected with IgG‐APS or with IgM‐APS with or without the inhibitor had medium–high titers of anticardiolipin antibodies in serum at the time of the surgical procedures. The data show that prothrombotic and proinflammatory properties of IgG‐APS and IgM‐APS are downregulated in vivo by an NF‐κB inhibitor. These findings may be important in designing new modalities of targeted therapies to treat thrombosis in patients with APS.
Are Antiphospholipid Antibodies an Essential Requirement for an Effective Immune Response to Infections?
Authors: Von LANDENBERG PHILIPP , DÖRING YVONNE , MODROW SUSANNE , LACKNER KARL J.
Published: October 2007

Abstract:  Antiphospholipid antibodies show a close association to a variety of infections. Recent data implicate that parvovirus B19 may be used as a model‐system for studying the interaction of viral infection and the development of these autoantibodies. B19‐related diseases commonly associated with the acute infection show flu‐like symptoms, transient arthralgias, leukopenia and thrombocytopenia, and, in pregnant women, spontaneous abortion and hydrops fetalis. Hepatitis, myocarditis, meningitis, encephalitis, as well as pure red cell anemia may occur occasionally. In addition, parvovirus B19 infections have been frequently described as the cause or trigger of various forms of autoimmune diseases affecting all blood cell lines, joints, connective tissue, uvea, and large and small vessels. Molecular mimicry may be one major contribution to the appearance of autoimmune antibodies, for example, antiphospholipid and antineutrophil cytoplasmic antibodies as well as antinuclear antigens. These mechanisms implicated in the pathogenesis of parvovirus B19‐triggered autoimmune diseases, especially focused on the development of antiphospholipid antibodies, will be discussed in this mini review.
Autoantibodies in Nonautoimmune Individuals during Infections
Authors: BERLIN TATIANA , ZANDMAN‐GODDARD GISELE , BLANK MIRI , MATTHIAS TORSTEN , PFEIFFER SASCHA , WEIS INGRID , TOUBI ELIAS , SINGH SHAM , ASHERSON RONALD , FRASER ABIGAIL , GILBURD BORIS , SAPIR TAL , LEVY YAIR , LUKAČ JANJA , ROZMAN BLAŽ , KVEDER TANJA , SHOENFELD YEHUDA
Published: October 2007

Abstract:  Infections can act as environmental triggers inducing or promoting autoimmune disease in genetically predisposed individuals. Identification of microbial peptides similar to self‐tissues may by molecular mimicry, provide the inducing mechanism for an immune response. The aim of this study was to identify autoantibodies (autoAbs) in nonautoimmune individuals during acute bacterial, viral, or parasitic infections. Specific Abs or specific infections with an increased autoAb load may shed insight into the mechanisms of autoimmune disease. Sera from 88 patients with acute infections (41 bacterial, 23 viral, 17 parasitic, and 7 rickettsial) were tested by the ELISA method for antinuclear antibodies (ANA) 8 Pro, and Abs to thyroid peroxidase (TPO), thyroglobulin, phospholipids, annexin‐V, laminin, anti–Saccharomyces cervisiae (ASCA), and prothrombin, along with 80 normal controls. Elevated titers of Abs to annexin‐V and prothrombin were the most prevalent in viral, parasitic, and rickettsial infections and to laminin in viral and parasitic infections. Elevated titers of ASCA and ANA were found in viral and bacterial infections. Antiphospholipid Abs were found in parasitic and Q‐fever infections. Thirty‐four individuals harbored elevated titers of at least two Abs. An autoAb burden was detected in individuals with hepatitis A, hepatitis B, toxoplasma or Q‐fever infections. In nonautoimmune individuals with various (bacterial, viral, parasitic, and rickettsial) infections, elevated titers of Abs to annexin‐V, prothrombin, laminin, ASCA, ANA, and phospholipids were most frequently detected.
Chronic Infections and Atherosclerosis
Authors: AYADA KIYOSHI , YOKOTA KENJI , KOBAYASHI KAZUKO , SHOENFELD YEHUDA , MATSUURA EIJI , OGUMA KEIJI
Published: October 2007

Abstract:  Immunoinflammatory processes due to chronic infection are thought to be one of the definitive atherogenetic processes. Especially, anti‐heat shock protein antibodies have been related to the prevalence of disease such as coronary artery disease or cerebral infarction, etc., resulted from atherosclerosis. Furthermore, the presence of HSP60‐specific T lymphocytes in circulation may increase the risk of atherosclerosis. We have recently demonstrated the evidences that Helicobacter pylori infection induced atherosclerosis in apoe+/−ldlr+/− mice and that Hp‐anti‐heat‐shock protein specific Th1‐dominant immune responses had a major involvement in the progression of atherosclerosis. These cellular immune responses caused autoimmunity against endogenous HSP60 (expressed on the stressed cells of vascular endothelium), due to the molecular mimicry. Therefore, an appropriate treatment with antibiotics or with anti‐HSP60 antibodies, which regulates the Th1 induction, could sufficiently reduce the progression of atherosclerosis.
Chronic Idiopathic Granulomatous Mastitis
Authors: KATZ URIEL , MOLAD YAIR , ABLIN JACOB , BEN‐DAVID DEBBY , PARAN DAPHNA , GUTMAN MORDECHAI , LANGEVITZ PNINA
Published: October 2007

Abstract:  We describe four women with idiopathic granulomatous mastitis, a rare benign disease. Age range was 32–40 years. Disease duration was less than 1 year in three patients and long term in the fourth. The diagnosis was based on histological findings, after extensive work‐up ruled out malignancy and known causes of granulomatous mastitis. Treatment with prednisone with gradual tapering yielded a good response. Clinicians should consider the possibility of idiopathic granulomatous mastitis in young women with inflammatory breast processes and negative findings on relevant biopsy, laboratory, and imaging studies. Glucocorticoids are the treatment of choice; surgery is not recommended. Some patients require a glucocorticoid‐sparing drug.
Renewal of singularity sets of random self-similar measures
Authors: Barral Julien , Seuret Stéphane
Published: October 2007

This paper investigates new properties concerning the multifractal structure of a class of random self-similar measures. These measures include the well-known Mandelbrot multiplicative cascades, sometimes called independent random cascades. We evaluate the scale at which the multifractal structure of these measures becomes discernible. The value of this scale is obtained through what we call the growth speed in Hölder singularity sets of a Borel measure. This growth speed yields new information on the multifractal behavior of the rescaled copies involved in the structure of statistically self-similar measures. Our results are useful in understanding the multifractal nature of various heterogeneous jump processes.
Continuous-time methods in the study of discretely sampled functionals of Lévy processes. I. The positive process case
Authors: Schröder Michael
Published: October 2007

In this paper we develop a constructive approach to studying continuously and discretely sampled functionals of Lévy processes. Estimates for the rate of convergence of the discretely sampled functionals to the continuously sampled functionals are derived, reducing the study of the latter to that of the former. Laguerre reduction series for the discretely sampled functionals are developed, reducing their study to that of the moment generating function of the pertinent Lévy processes and to that of the moments of these processes in particular. The results are applied to questions of contingent claim valuation, such as the explicit valuation of Asian options, and illustrated in the case of generalized inverse Gaussian Lévy processes.
Distribution-Invariant Risk Measures, Entropy, and Large Deviations
Authors: Weber Stefan
Published: October 2007

The simulation of distributions of financial assets is an important issue for financial institutions. If risk measures are evaluated for a simulated distribution instead of the model-implied distribution, the errors in the risk measurements need to be analyzed. For distribution-invariant risk measures which are continuous on compacts, we employ the theory of large deviations to study the probability of large errors. If the approximate risk measurements are based on the empirical distribution of independent samples, then the rate function equals the minimal relative entropy under a risk measure constraint. We solve this minimization problem explicitly for shortfall risk and average value at risk.
On Generating Functions of Waiting Times and Numbers of Occurrences of Compound Patterns in a Sequence of Multistate Trials
Authors: Inoue Kiyoshi , Aki Sigeo
Published: October 2007

In this paper we study two distributions, namely the distribution of the waiting times until given numbers of occurrences of compound patterns and the distribution of the numbers of occurrences of compound patterns in a fixed number of trials. We elucidate the interrelation between these two distributions in terms of the generating functions. We provide perspectives on the problems related to compound patterns in statistics and probability. As an application, the waiting time problem of counting runs of specified lengths is considered in order to illustrate how the distributions of waiting times can be derived from our theoretical results.
Mean Residual Lifetimes of Consecutive-k-out-of-n Systems
Authors: Navarro Jorge , Eryilmaz Serkan
Published: October 2007

In this paper we study reliability properties of consecutive-k-out-of-n systems with exchangeable components. For 2k ≦ n, we show that the reliability functions of these systems can be written as negative mixtures (i.e. mixtures with some negative weights) of two series (or parallel) systems. Some monotonicity and asymptotic properties for the mean residual lifetime function are obtained and some ordering properties between these systems are established. We prove that, under some assumptions, the mean residual lifetime function of the consecutive-k-out-of-n: G system (i.e. a system that functions if and only if at least k consecutive components function) is asymptotically equivalent to that of a series system with k components. When the components are independent and identically distributed, we show that consecutive-k-out-of-n systems are ordered in the likelihood ratio order and, hence, in the mean residual lifetime order, for 2k ≦ n. However, we show that this is not necessarily true when the components are dependent.
On Two Damage Accumulation Models and Their Size Effects
Authors: Ballani F. , Stoyan D. , Wolf S.
Published: October 2007

Two cumulative damage models are considered, the inverse gamma process and a composed gamma process. They can be seen as ‘continuous’ analogues of Poisson and compound Poisson processes, respectively. For these models the first passage time distribution functions are derived. Inhomogeneous versions of these processes lead to models closely related to the Weibull failure model. All models show interesting size effects.
Study of a Stochastic Failure Model in a Random Environment
Authors: Cha Ji Hwan , Mi Jie
Published: October 2007

Most devices (systems) are operated under different environmental conditions. The failure process of a system not only depends on the intrinsic characteristics of the system itself but also on the external environmental conditions under which the system is being operated. In this paper we study a stochastic failure model in a random environment and investigate the effect of the environmental factors on the failure process of the system.
On Optimality of Bold Play for Discounted Dubins-Savage Gambling Problems with Limited Playing Times
Authors: Yao Yi-Ching
Published: October 2007

In the classic Dubins-Savage subfair primitive casino gambling problem, the gambler can stake any amount in his possession, winning (1 - r)/r times the stake with probability w and losing the stake with probability 1 - w, 0 ≤ w ≤ r ≤ 1. The gambler seeks to maximize the probability of reaching a fixed fortune by gambling repeatedly with suitably chosen stakes. This problem has been extended in several directions to account for limited playing time or future discounting. We propose a unifying framework that covers these extensions, and prove that bold play is optimal provided that w ≤ ½ ≤ r. We also show that this condition is in fact necessary for bold play to be optimal subject to the constraint of limited playing time.
A Class of MultidimensionalQ-Processes
Authors: Wu Bo , Zhang Yu-Hui
Published: October 2007

In this paper we present some necessary conditions for the uniqueness, recurrence, and ergodicity of a class of multidimensionalQ-processes, using the dual Yan-Chen comparison method. Then the coupling method is used to study the multidimensional processes in a specific space. As applications, three models of particle systems are illustrated.
A Note on Insensitivity in Stochastic Networks
Authors: Zachary Stan
Published: October 2007

We give a simple and direct treatment of insensitivity in stochastic networks which is quite general and provides probabilistic insight into the phenomenon. In the case of multi-class networks, our results generalise those of Bonald and Proutière (2002), (2003).
Heavy Tails of Discounted Aggregate Claims in the Continuous-Time Renewal Model
Authors: Tang Qihe
Published: October 2007

We study the tail behavior of discounted aggregate claims in a continuous-time renewal model. For the case of Pareto-type claims, we establish a tail asymptotic formula, which holds uniformly in time.
Convolution Equivalence and Infinite Divisibility: Corrections and Corollaries
Authors: Pakes Anthony G.
Published: October 2007

Corrections are made to formulations and proofs of some theorems about convolution equivalence closure for random sum distributions. These arise because of the falsity of a much used asymptotic equivalence lemma, and they impinge on the convolution equivalence closure theorem for general infinitely divisible laws.
A Paradox for Admission Control of Multiclass Queueing Network with Differentiated Service
Authors: Ye Heng-Qing
Published: October 2007

In this paper we present counter-intuitive examples for the multiclass queueing network, where each station may serve more than one job class with differentiated service priority and each job may require service sequentially by more than one service station. In our examples, the network performance is improved even when more jobs are admitted for service.
Tail Asymptotics of the Supremum of a Regenerative Process
Authors: Palmowski Zbigniew , Zwart Bert
Published: October 2007

We give precise asymptotic estimates of the tail behavior of the distribution of the supremum of a process with regenerative increments. Our results cover four qualitatively different regimes involving both light tails and heavy tails, and are illustrated with examples arising in queueing theory and insurance risk.
On Long-Range Dependence in Regenerative Processes Based on a General ON/OFF Scheme
Authors: Leipus Remigijus , Surgailis Donatas
Published: October 2007

In this paper, we obtain a closed form for the covariance function of a general stationary regenerative process. It is used to derive exact asymptotics of the covariance function of stationary ON/OFF and workload processes, when ON and OFF periods are heavy-tailed and mutually dependent. The case of a G/G/1/0 queueing system with heavy-tailed arrival and/or service times is studied in detail.
On the Pricing of American Options in Exponential Lévy Markets
Authors: Ivanov Roman V.
Published: October 2007

In this paper, we discuss the problem of the pricing of American-style options in the exponential Lévy security market model. This model is typically incomplete, and we derive the explicit bounds of the interval of no arbitrage prices and the related optimal stopping moments for American put options and American call options in both finite and infinite horizon time. We consider a large class of Lévy processes.
Distributional Study of De Finetti's Dividend Problem for a General Lévy Insurance Risk Process
Authors: Kyprianou A. E. , Palmowski Z.
Published: October 2007

We provide a distributional study of the solution to the classical control problem due to De Finetti (1957), Gerber (1969), Azcue and Muler (2005), and Avram et al. (2007), which concerns the optimal payment of dividends from an insurance risk process prior to ruin. Specifically, we build on recent work in the actuarial literature concerning calculations of the nth moment of the net present value of dividends paid out in the optimal strategy as well as the moments of the deficit at ruin and the Laplace transform of the red period. The calculations we present go much further than the existing literature, in that our calculations are valid for a general spectrally negative Lévy process as opposed to the classical Cramér–Lundberg process with exponentially distributed jumps. Moreover, the technique we use appeals principally to excursion theory rather than integro-differential equations and, for the case of the nth moment of the net present value of dividends, makes a new link with the distribution of integrated exponential subordinators.
Coupling and Ergodicity of Adaptive Markov Chain Monte Carlo Algorithms
Authors: Roberts Gareth O. , Rosenthal Jeffrey S.
Published: October 2007

We consider basic ergodicity properties of adaptive Markov chain Monte Carlo algorithms under minimal assumptions, using coupling constructions. We prove convergence in distribution and a weak law of large numbers. We also give counterexamples to demonstrate that the assumptions we make are not redundant.
Computable Bounds for the Decay Parameter of a Birth–Death Process
Authors: Sirl David , Zhang Hanjun , Pollett Phil
Published: October 2007

We present bounds on the decay parameter for absorbing birth–death processes adapted from results of Chen (2000), (2001). We address numerical issues associated with computing these bounds, and assess their accuracy for several models, including the stochastic logistic model, for which estimates of the decay parameter have been obtained previously by Nåsell (2001).
Explicit Gittins Indices for a Class of Superdiffusive Processes
Authors: Filliger Roger , Hongler Max-Olivier
Published: October 2007

We explicitly calculate the dynamic allocation indices (i.e. the Gittins indices) for multi-armed Bandit processes driven by superdiffusive noise sources. This class of model generalizes former results derived by Karatzas for diffusive processes. In particular, the Gittins indices do, in this soluble class of superdiffusive models, explicitly depend on the noise state.