Publications (43)202.87 Total impact
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Article: Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways.
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ABSTRACT: Activation of coagulation and fibrinolysis play a role in the pathophysiology of experimental arthritis. Objective: To determine the extent of activation of the coagulation and fibrinolytic pathways in different joint diseases in humans and to ascertain the factors that may influence fibrin deposition within the joint. Plasma from normal subjects (controls, n= 21) and plasma and synovial fluid samples from patients with rheumatoid arthritis (RA; n = 64), osteoarthritis (OA; n = 29), spondyloarthropathy (SpA; n = 22) and crystal arthritis (CA; n = 25) were analyzed for the levels of TF (tissue factor) and tissue factor pathway inhibitor (TFPI) activities, thrombin-antithrombin III (TAT) complexes, and F1 + 2 (thrombin fragment), fibrin d-dimer and thrombin-activated fibrinolysis inhibitor (TAFI) antigenic levels. The measurements were analyzed by pairwise correlation with each other as well as with standard parameters of inflammation [C-reactive protein (CRP), joint leukocyte count]. Inter-group comparisons were performed to look for disease-specific differences. Compared with healthy controls, patients with joint diseases had higher levels of TAT, F1 + 2 and d-dimers in their plasma. In the synovial fluid, TF activity, TAT, d-dimers, and TAFI were significantly higher in inflammatory arthritides than in OA. The levels were highest in RA patients. In the plasma, TF activity was correlated with TAT and d-dimer levels with CRP, TFPI, and TAT. In the synovial fluid, TF activity correlated with plasma CRP levels, synovial fluid leukocyte count, and synovial TAT and TAFI levels. In addition, synovial d-dimers correlated with CRP, and synovial TAFI levels were correlated with synovial F1 + 2 and TAT. Activation of the coagulation and fibrinolytic cascades in the joint and in the circulation is evident in both inflammatory and degenerative joint diseases. Within the joint, inflammatory mechanisms leading to TF-mediated activation of the coagulation pathway and subsequent fibrin deposition is the most likely explanation for the observed findings. In the plasma, the link between inflammation (CRP increase) and TF activation is weak, and a non-TF-mediated mechanism of coagulation activation could explain these findings. RA is characterized by significantly higher levels of TAT in the synovial fluid and plasma than other arthritides. Although fibrinolytic activity is linked to inflammation, the increased amounts of TAFI in the joint, particularly in RA, may explain why fibrin formation is so prominent in this condition compared with other joint diseases.Journal of Thrombosis and Haemostasis 01/2004; 1(12):2510-5. · 5.73 Impact Factor -
Article: Plasma apolipoprotein(a) co-deposits with fibrin in inflammatory arthritic joints.
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ABSTRACT: Extravascular coagulation and diminished fibrinolysis are processes that contribute to the pathology of both inflammatory arthritis and atherosclerosis. We hypothesized that, given its homology with plasminogen, apolipoprotein (apo) (a), the distinctive glycoprotein of the atherogenic lipoprotein (Lp) (a), may be equally implicated in inflammatory arthritis. We detected the presence of apo(a) as part of Lp(a) in human arthritic synovial fluid. The abundance of apo(a) in synovial fluid rose in proportion to plasma apo(a) levels and was higher in inflammatory arthritides than in osteoarthritis. In addition, apo(a) immunoreactive material, but not apo(a) transcripts, was detected in inflammatory arthritic synovial tissues. These data indicated that synovial fluid apo(a) originates from circulating Lp(a) and that diffusion of Lp(a) through synovial tissue is facilitated in inflammatory types of arthritis. In synovial tissues, apo(a) co-localized with fibrin. These observations could be reproduced in a model of antigen-induced arthritis, using transgenic mice expressing human Lp(a). Although in this mouse model the presence of apo(a) did not change the severity of arthritis, the co-localization of apo(a) with fibrin in synovial tissue suggests that, in humans, apo(a) may modulate locally the fibrinolytic activity and may thus contribute to the persistence of intra-articular fibrin in inflammatory arthritis.American Journal Of Pathology 11/2001; 159(4):1445-53. · 4.89 Impact Factor -
Article: Identification of case complexity and increased health care utilization in patients with rheumatoid arthritis.
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ABSTRACT: To document biopsychosocial profiles of patients with rheumatoid arthritis (RA) by means of the INTERMED and to correlate the results with conventional methods of disease assessment and health care utilization. Patients with RA (n = 75) were evaluated with the INTERMED, an instrument for assessing case complexity and care needs. Based on their INTERMED scores, patients were compared with regard to severity of illness, functional status, and health care utilization. In cluster analysis, a 2-cluster solution emerged, with about half of the patients characterized as complex. Complex patients scoring especially high in the psychosocial domain of the INTERMED were disabled significantly more often and took more psychotropic drugs. Although the 2 patient groups did not differ in severity of illness and functional status, complex patients rated their illness as more severe on subjective measures and on most items of the Medical Outcomes Study Short Form 36. Complex patients showed increased health care utilization despite a similar biologic profile. The INTERMED identified complex patients with increased health care utilization, provided meaningful and comprehensive patient information, and proved to be easy to implement and advantageous compared with conventional methods of disease assessment. Intervention studies will have to demonstrate whether management strategies based on INTERMED profiles can improve treatment response and outcome of complex patients.Arthritis & Rheumatism 07/2001; 45(3):216-21. · 7.87 Impact Factor -
Article: Secondary amyloidosis: a severe complication of ankylosing spondylitis. Two case-reports.
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ABSTRACT: To report two cases of amyloidosis secondary to ankylosing spondylitis. Of the 47 ankylosing spondylitis patients who have received follow-up at our department over the last few years, two have developed AA amyloidosis. Both have extremely severe, long-standing joint disease, with virtually complete spinal ankylosis and destructive peripheral arthritis of the hips and wrists; one also has tarsal joint destruction. Renal dysfunction was the first manifestation of amyloidosis in both cases. One patient required chronic hemodialysis and developed peritonitis due to colonic perforation, probably at a site of amyloid deposition. Secondary amyloidosis is a rare complication of ankylosing spondylitis that can cause severe renal and gastrointestinal complications. No treatment capable of clearing established amyloid deposits is available to date.Joint Bone Spine 02/2000; 67(2):129-33. · 2.27 Impact Factor -
Article: [Prognostic aspects of scintigraphy and MRI during the first 6 months of reflex sympathetic dystrophy of the distal lower limb: a preliminary prospective study of 4 cases].
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ABSTRACT: The appearance of scintigraphic and magnetic resonance imaging during the evolution of reflex sympathetic dystrophy of the foot is not well known and subject to controversies. The purpose of this preliminary study is to compare these two types of investigation during the first 6 months of evolution. 4 non-selected patients with a diagnosis of acute reflex sympathetic dystrophy of the foot (no more than 2 months of evolution and more than 3 out of 6 clinical criteria suggesting a "warm" phase) were studied prospectively. A clinical evaluation, scintigraphy and magnetic resonance imaging (MRI) were performed at diagnosis and after 3 and 6 months. All available examinations (n = 22) were analyzed independently by independent observers. Clinically 3 of 4 patients developed or previously had another site of sympathetic dystrophy confirmed by total body scintigraphy. After 6 months 2 of 4 patients still have a "warm" dystrophy. Bone scanning showed localized or diffuse tracer uptake and MRI showed bone and soft tissue edema when the sympathetic dystrophy was and/or remained clinically "warm". MRI bone edema moved from one location to another in 3 of 4 patients during the follow-up. There was a good correlation between bone scan and MRI images. In "warm" dystrophy, MRI was positive 5 out of 7 times and scintigraphy in all cases. Bone edema and tracer uptake faded simultaneously although the latter was more diffuse and more persistent than the former. MRI as well as bone scintigraphy are suitable for the diagnosis of warm dystrophy of the foot. Both exams remain positive when the dystrophy is still "warm" after 6 months. The radiographic evolution after 6 months still has to be evaluated.Journal de Radiologie 05/1999; 80(4):373-7. · 0.42 Impact Factor -
Article: T cells and related cytokines.
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ABSTRACT: T cells play a critical role in rheumatoid arthritis. They are probably continuously involved in pathogenesis, from the initiation to the chronic stage. As recent studies have demonstrated, the part they play in rheumatoid arthritis is closely linked to the roles of macrophages and mesenchymal cells, because they all interact through autocrine, paracrine, and cell-contact pathways. This paper reviews recent work and research regarding the specific role of T cells in the pathogenesis of rheumatoid arthritis.Current Opinion in Rheumatology 06/1998; 10(3):207-11. · 4.31 Impact Factor -
Article: T-cell receptor variable alpha (TCRAV) polymorphisms in European, Chinese, South American, AfroCaribbean, and Gambian populations.
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ABSTRACT: Interactions involving the T-cell receptor (TCR) and major histocompatibility complex (MHC) are fundamental to the generation of a specific immune response. The study of interpopulation differences in TCR genes may identify those genes which are subject to selection, and also provides useful information for future genetic studies in these populations. In this study we present analysis of five TCRAV polymorphisms, for V5S1, V6S1, V8S1, V17S1, and V21S1 loci in five human populations by single-strand conformational polymorphism (SSCP) analysis. Caucasian, Chinese, Gambian, AfroCaribbean, and South American Indians (Mapuches) showed marked interpopulation variation for both the silent (V5S1, V17S1, and V21S1) and coding (V6S1 and V8S1) polymorphisms. In general the alleles were conserved in the different populations, but new, additional variants were found for V5S1 and V17S1 in Gambians and Caucasians. V6S1 overall showed the highest nucleotide diversity, and V6S1 genotype distributions were skewed away from expected values in Chinese and Mapuches. Analysis of allelic associations showed a general lack of linkage disequilibrium between the loci, which was reflected by the absence of strong population-specific haplotypes.Immunogenetics 02/1998; 47(2):124-30. · 2.93 Impact Factor -
Article: Analysis of T cell receptor V alpha polymorphisms in rheumatoid arthritis.
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ABSTRACT: To test for association of T cell receptor (TCR) V alpha polymorphisms and rheumatoid arthritis (RA) in British and Swiss white populations. TCRAV polymorphisms were analysed in RA patients and controls by single strand conformational polymorphism (SSCP) analysis. Associations were sought between defined genotypes and RA, and the effect of HLA-DR4 status analysed. Putative associations were then retested further in new groups of patients and controls. Overall, 360 RA patients and 197 controls were studied. No association between TCRAV5S1, V6S1, V8S1, V17S1 or V21S1 polymorphisms and RA were observed in the initial population screened. Stratification for DR4 status showed an increase of V5S1*01/*01 in DR4 positive versus DR4 negative patients (chi 2 = 7.19, p = 0.028 (2df), p = 0.14 after correction for multiple comparisons). This putative association was tested in three further patient groups, none of which showed significant increase of V5S1*01/*01 in DR4 positive patients, although an overall trend towards an increase in V5S1*01/*01 was observed. No evidence was found for a strong association of TCRAV genes and RA in a white population. However, these results suggest a weak association of V5S1*01/*01 with DR4 positive RA, although this requires confirmation using larger groups of patients and controls.Annals of the Rheumatic Diseases 01/1998; 57(1):49-51. · 8.73 Impact Factor -
Article: Vasculitis and bacteraemia with Yersinia enterocolitica in late-onset systemic lupus erythematosus.
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ABSTRACT: We report a case of Yersinia enterocolitica 0.9 septicaemia complicating systemic lupus erythematosus in an elderly male patient. The infection gave rise to digital vasculitis, fevers and general malaise on top of pre-existing articular symptoms. Features of Yersinia septicaemia may mimic some of the signs of lupus.British journal of rheumatology 11/1997; 36(10):1122-4. -
Article: Anti-PL 4 in patients with systemic lupus erythematosus with severe renal and haematological disease.
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ABSTRACT: Anti-PL 4 is an autoantibody which binds to a 150 kDa polypeptide and is found in approximately 1% of SLE sera. The clinical and laboratory features of 16 patients who have had anti-PL 4 detected in their serum are presented. Anti-PL 4 is highly specific for SLE (100%) and identifies a population of patients who typically develop severe renal (75%) and haematological disease (100%).QJM: monthly journal of the Association of Physicians 06/1997; 90(5):347-52. · 2.33 Impact Factor -
Article: Similarities of specificity and cofactor dependence in serum antiphospholipid antibodies from patients with human parvovirus B19 infection and from those with systemic lupus erythematosus.
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ABSTRACT: To assess the phospholipid specificity and immunoglobulin isotype of antiphospholipid (aPL) antibodies in patients with acute parvovirus B19 infection. Specificity of aPL and isotype distribution in the negatively charged phospholipids, cardiolipin and phosphatidyl serine, and in the neutral phospholipid, phosphatidyl ethanolamine, were measured in the sera of patients with acute parvovirus B19 infections (n = 12), in those with other acute viral infections (n = 10), and in those with syphilis (n = 15) by enzyme-linked immunosorbent assays. The dependence of anticardiolipin (aCL) binding on the presence of beta 2-glycoprotein I (beta 2-GPI) as a binding cofactor was assessed in these same groups, and was compared with sera from systemic lupus erythematosus (SLE) patients (n = 11) with raised aCL antibody reactivity. Antibodies against any of the 3 phospholipids were found in all 3 groups of patients with infections (B19 in 11 of 12 patients, other viral infections in 8 of 10 patients, and syphilis in 14 of 15 patients). B19 patients' sera contained predominantly IgG antibodies against the negatively charged phospholipids, cardiolipin and phosphatidyl serine, and differed in their specificity and isotype distribution from those found in the other 2 patient groups. B19-associated aCL increased their binding to antigen in the presence of beta 2-GPI as a binding cofactor, similar to aCL found in SLE patients, but unlike antibodies from patients with other viral infections or from those with syphilis. The results show the remarkable similarity in specificity of aPL antibodies between B19-infected patients and SLE patients, and raise the question of whether parvovirus infection may be a trigger for the development of aPL antibodies in autoimmune diseases.Arthritis & Rheumatism 02/1997; 40(1):103-8. · 7.87 Impact Factor -
Article: Back pain in the older patient.
Annals of the Rheumatic Diseases 10/1996; 55(9):600-2. · 8.73 Impact Factor -
Article: A human monoclonal antiphospholipid antibody that is representative of serum antibodies and is germline encoded.
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ABSTRACT: To investigate the origins of antiphospholipid antibodies associated with thrombosis and other disorders that are found in patients with systemic lupus erythematosus and primary antiphospholipid syndrome (APS). Characterization, idiotypic study, and nucleotide sequencing of a human monoclonal antiphospholipid antibody generated from a patient with primary APS. Identification of the germline genes from which the antibody is derived. A human monoclonal antibody, BH1, was generated. This antibody has ligand-binding properties that closely resemble those of the serum antiphospholipid antibodies found in our patient and in other individuals with APS: it recognizes negatively charged phospholipids, and has lupus anticoagulant activity; it does not bind to neutral phospholipids, or to single-stranded or double-stranded DNA. The relevance of BH1 to the patient's serum antibodies is supported by our idiotypic studies. BH1 is encoded by a new germline VH gene, and by a lambda light chain gene that displays > 99% homology with the V lambda III.1 germline gene. Serum antiphospholipid antibodies associated with thrombosis may be encoded by either germline or only slightly mutated variable-region genes.Arthritis & Rheumatism 08/1995; 38(8):1068-76. · 7.87 Impact Factor -
Article: Genomic organization of the human T-cell receptor variable alpha (TCRAV) gene cluster.
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ABSTRACT: A long-range physical map of the human T-cell receptor variable alpha (TCRAV) locus was produced using 23 V alpha subgroup-specific probes. Linkage disequilibrium across the locus was also studied using polymorphic TCRAV markers. Pulsed-field gel electrophoresis was used to map V alpha gene segments onto one SfiI fragment of 500 kb and two of 200 kb using DNA from peripheral blood neutrophils. PCR and conventional Southern techniques on Jurkat, CEM, and H9 T-cell lines were used to establish the 5' to 3' order of the gene segments and the relative positions of V alpha gene segments on the SfiI fragments. The linkage disequilibrium study used single-stranded conformation polymorphism analysis to genotype 100 normal caucasoid subjects for TCRAV5S1, V6S1, V8S1, V17S1, and V21S1 polymorphisms. Strong linkage disequilibrium was detected between V5S1 and V8S1, in concordance with the physical map. This new information will be useful for future studies of genetic variation at the TCRAV locus, its role in the shaping of the TCR repertoire, and its possible contribution to autoimmune diseases.Genomics 08/1995; 28(2):131-9. · 3.02 Impact Factor -
Article: No association between HLA-DQ and -DR genotypes with nasopharyngeal carcinoma in southern Chinese.
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ABSTRACT: The pathogenesis of nasopharyngeal carcinoma (NPC) is multifactorial. Associations have been reported between HLA and NPC. We studied the HLA-DR and -DQ regions on the molecular level in 136 persons (51 NPC patients and 85 healthy controls) from southern China, a particularly high-prevalence area for NPC. Restriction fragment-length polymorphism (RFLP) was used to genotype the MHC class II DR beta, DQ alpha, and DQ beta regions of the subjects. Polymerase chain reaction (PCR) using sequence-specific primer (SSP) for DQ beta genes was also performed. By RFLP, no significant difference was observed with respect to DRB, DQA, and DQB genes. By PCR SSP typing, we confirmed that there was no significant difference between NPC patients and controls with respect to DQ beta alleles. Our study suggests that HLA-DQ and -DR genes are not associated with NPC in southern Chinese and there may be other gene loci that predispose them to have such a high prevalence of the disease.Cancer Genetics and Cytogenetics 06/1995; 81(1):42-5. · 1.39 Impact Factor -
Article: CD4 T cells in the rheumatoid joint are oligoclonally activated and change during the course of disease.
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ABSTRACT: To assess the nature of T cell receptor (TCR) utilisation by CD4 T cells in the rheumatoid joint. Sequencing of the joining (NDJ) region of TCR beta chain mRNA isolated from synovial fluid CD4 T cells was performed in three patients in order to determine if oligoclonal expansion of particular sequences was present. Two patients were studied longitudinally to determine if these sequences changed over time. A number of dominant clonotypes were found within the TCR transcripts sequenced in each patient. In the two patients who were studied longitudinally, different dominant clonotypes were detected over time. No single clonotype was persistently dominant during the period of study. The pattern of TCR usage showed multiple oligoclonally expanded CD4 T cells within the rheumatoid joint. The change in clonotypes within the joint over time suggests that different antigens may be able to elicit synovial inflammation during the course of rheumatoid disease.Annals of the Rheumatic Diseases 05/1995; 54(4):314-7. · 8.73 Impact Factor -
Article: Physical mapping of the human T-cell receptor beta gene complex, using yeast artificial chromosomes.
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ABSTRACT: Yeast artificial chromosomes (YACs) were used to construct a physical map of the germline human T-cell beta chain gene complex (TCRB). Variable region genes (BV) for the 25 known subfamilies were used as probes to screen the ICRF AM4x YAC library. Of the five positive YACs identified, one YAC designated B3, 820 kilobase pairs (kbp) in size, scored positive for all 25 TCRBV subfamilies plus the constant region genes (BC) when analyzed by pulse field gel electrophoresis. Restriction enzyme mapping of B3 located TCRBV and TCRBC gene regions to 4 Sfi I fragments of 280 110, 90, and 125 kbp and was in accordance with published data. In addition comparison of hybridization results of Sfi I-restricted B3 and genomic DNA from the parental cell line GM1416B revealed identical banding patterns. The data thus showed YAC B3 encoded a complete and unrearranged TCRB gene locus of some 600-620 kbp. The map was further resolved by locating restriction sites for Sal I and Bss HII on B3, giving more precise localization of the individual TCRBV gene families. Fluorescent in situ hybridization of B3 to spreads of human metaphase chromosomes localized B3 to 7q35. However, two additional signals were obtained; one attributable to the TCRBV orphon cluster on 9p21, the second to the long arm of chromosome 2. Polymerase chain reaction amplification of a chromosome 2 somatic cell hybrid, using primers for all 25 TCRBV gene families, revealed that the signal was not attributable to a second orphon cluster. It is suggested that B3 is a chimeric YAC with an intact TCRB locus flanked by chromosome 2 sequences.Immunogenetics 02/1995; 41(6):337-42. · 2.93 Impact Factor -
Article: Lack of association of T cell receptor V beta 8 polymorphism with rheumatoid arthritis in United Kingdom and Italian white patients.
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ABSTRACT: To study if the reported association of a BamH I 2kb RFLP of the T cell receptor V beta 8 gene with DR4+ rheumatoid arthritis patients is found in non-American white populations. The frequency of this RFLP in two different populations was analysed. Eighty one northern Italians were studied for HLA-DR genotypes and V beta 8 polymorphism, and 29 DR4+ British white patients were studied for V beta 8 polymorphism. No association between the V beta 8 RFLP and DR4 was found with rheumatoid arthritis in both groups. The reported V beta 8-DR4 association is not generally applicable. The lack of association in our populations may be due to genetic differences, or to differences in factors which shaped the T cell repertoire.Annals of the Rheumatic Diseases 06/1994; 53(5):341-3. · 8.73 Impact Factor -
Article: An altered repertoire of T cell receptor V gene expression by rheumatoid synovial fluid T lymphocytes.
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ABSTRACT: The pattern of T cell receptor V gene expression by lymphocytes from rheumatoid synovial fluid and paired peripheral blood samples was compared using a polymerase chain reaction (PCR)-based assay. Eight rheumatoid arthritis (RA) patients who had varying durations of disease (from 2 to 20 years) were studied. In all patients there was evidence of a different pattern of V gene expression between the two compartments. Significantly increased expression of at least one V alpha or V beta gene family by synovial fluid T cells was observed in all the patients studied. Three different V alpha (V alpha 10, 15 and 18) and three V beta (V beta 4, 5 and 13) families were commonly elevated. Sequencing of synovial V beta transcripts demonstrated that the basis of increased expression of selected V gene families in the synovial fluid was due to the presence of dominant clonotypes within those families, which constituted up to 53% of the sequences isolated from one particular synovial V gene family. There were considerable differences in the NDJ sequences found in synovial and peripheral blood T cell receptor (TCR) transcripts of the same V beta gene family. These data suggest that the TCR repertoire in the two compartments differs, and that antigen-driven expansion of particular synovial T cell populations is a component of rheumatoid synovitis, and is present in all stages of the disease.Clinical & Experimental Immunology 01/1993; 90(3):440-6. · 3.36 Impact Factor -
Article: Familial IgA nephropathy: a study of HLA class II allogenotypes in a Chinese kindred.
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ABSTRACT: We have studied the restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) class II DQ, DR pattern of a Chinese family with IgA nephropathy (IgAN). The three affected and one apparently unaffected sibling shared the same DR and DQ pattern. The subjects were homozygous for DRw12, DQw7, DQ alpha 1b. The DQw7 allele was further confirmed by polymerase chain reaction (PCR) and allele-specific oligonucleotide (ASO) probing. This study confirms that IgAN can run in a family and is consistent with the possible immunopathogenetic effects of MHC class II antigens on IgAN.American Journal of Kidney Diseases 12/1992; 20(5):458-62. · 5.43 Impact Factor
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Institutions
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1996–2004
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University Hospital of Lausanne
Lausanne, VD, Switzerland
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1990–1998
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Ealing, Hammersmith & West London College
London, ENG, United Kingdom
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