Induction of anti-DNA antibodies by immunization with anti-DNA antibodies: mechanism and characterization

Two well-characterized IgG monoclonal antibodies, reactive with double-stranded (ds) DNA and nucleosomes, were administered to normal BALB/c mice to examine the reproducibility and the biology of a previously reported model of anti-DNA antibody induction by immunization with anti-DNA antibodies. The monoclonal antibodies were purified either with or without a high-salt wash to remove nucleosomal antigens bound to them during the cell culture. Both monoclonal antibodies, but not normal IgG, induced significant IgG anti-dsDNA antibody production from 1 week to 25 weeks after the last immunization. The antibodies produced in this manner possess different binding preferences to ds synthetic polynucleotides than the antibodies used for the immunization, and they did not react with nucleosomes. The monoclonal antibodies purified with the high-salt wash were more effective in anti-DNA antibody induction than those purified without the high-salt wash. Even when bound to these monoclonal antibodies, neither dsDNA, nucleosomes, or ds synthetic polynucleotides exert significant antigenicity. For example, anti-DNA antibodies produced by mice immunized with an immune complex formed by poly(dA-dT) and one of the monoclonal antibodies that has a high affinity to this polynucleotide did not show an increased affinity to poly(dA-dT). Together, these results suggest that anti-DNA antibody molecules or processed antibody peptides, and not DNA/nucleosomes carried by anti-DNA antibodies, play a role in this model of anti-DNA antibody production.     

Evolution of social organization: a reappraisal for primates by using phylogenetic methods.

For many animal taxa, the extent to which phylogeny can account for the form of species' social systems has seldom been investigated formally. A quantitative phylogenetic analysis of social systems in the order Primates reveals that social organization may be strongly conserved in some lineages, even in the face of considerable ecological variability. This result has important implications for efforts to understand the evolution of animal societies and for attempts to reconstruct the social organization of early humans.     

Growth stimulating antibodies in endemic goitre: a reappraisal

OBJECTIVE Previous studies, using a variety of methods, have reported growth-promoting Immunoglobulins (IGs) In a large proportion of patients with endemic goitre. We sought to determine whether thyroid growth-promoting Immunoglobulins (TGI) are present in the serum of Indian patients with endemic goitre. DESIGN IgG was prepared by protein G-Sepharose affinity purification and added to FRTL-5 thyroid cells In the presence of suboptimal concentrations of TSH. PATIENTS We studied 30 sequential patients with endemic goitre and 16 euthyroid controls without a goitre from the same area MEASUREMENTS Two assays for thyroid cell growth were used: ³H-thymldine Incorporation, and flow cytometric measurement of the proportion of cells in the S phase and G₂/M phase of the cell cycle. RESULTS Both assays were shown to detect growth produced by TSH and by thyroid stimulating antibodies in IgG preparations from 3 patients with Graves' disease. There was no significant Increase In either ³H-thymldine Incorporation or the distribution of cells In S or G₂/M phase with IgGs from endemic goitre patients, and no difference between the effects of these IgGs and those from the normal subjects. CONCLUSIONS Thyroid growth-promoting immunoglobulins cannot be detected In Indian patients with endemic goitre.     

Comparison of five different tests for mumps antibodies

Summary Pre- and postvaccination sera from 32 children aged 1.5 to 2 years vaccinated with two different mumps vaccines were available for the determination of mumps antibodies. Five different tests for mumps antibodies were performed: serum neutralisation, haemagglutination inhibition, the enzyme-linked immunosorbent assay (ELISA), single radial haemolysis and immunofluorescence. For the evaluation of the tests, the results of serum neutralisation were used as a standard and compared with those of the other four methods. Immunofluorescence proved to be the most reliable method, followed by ELISA and haemagglutination inhibition, whereas single radial haemolysis showed the most deviations from seroneutralisation.

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Vergleich von fünf verschiedenen Bestimmungsmethoden für Mumpsantikörper

Zusammenfassung Von zweiunddreißig Kindern im Alter von eineinhalb bis zwei Jahren, die mit zwei verschiedenen Mumpsimpfstoffen geimpft worden waren, war je eine Serumprobe vor und nach Impfung für die Bestimmung von Mumpsantikörper verfügbar. Die Mumpsantikörper wurden mit fünf verschiedenen Techniken bestimmt: Serumneutralisation, Hämagglutinationshemmung, ELISA, radiale Hämolyse und Immunfluoreszenz. Für die Auswertung der Resultate wurden die Ergebnisse der Serumneutralisation als Leitlinie verwendet und mit denen der vier übrigen Methoden verglichen. Dabei erwies sich die Immunfluoreszenz als die zuverlässigste Methode, gefolgt von ELISA und Hämagglutinationshemmung, während die radiale Hämolyse die meisten Abweichungen von der Serumneutralisation zu verzeichnen hatte.

     

Stent-graft migration: a reappraisal of analysis methods and proposed revised definition.

PURPOSE: To demonstrate the need for a radiographic definition of migration that accurately describes a specific failure mode of an aortic stent-graft. METHODS: The diagnosis of endograft migration, as defined by the Society for Vascular Surgery/American Association for Vascular Surgery (SVS/AAVS) standards, requires a synthesis of clinical and/or radiographic observations. Radiographic studies and clinical reports of 704 consecutive patients treated over a 6-year period with abdominal aortic endografts were retrospectively reviewed. According to the current SVS/AAVS standards, 25 patients were identified as having endograft migration. Follow-up computed tomographic scans and radiographs available for 24 of these patients were scrutinized from discharge to the time of any observed proximal or distal fixation system movement based upon the discharge or 30-day CT scan. Proximal migration was defined with respect to the origin of the superior mesenteric artery (SMA) as movement in a caudal or cranial direction of >/=10 mm or >2 times the reconstructed resolution of the imaging study (whichever measurement was less). Distal migration was similarly defined using the aortic bifurcation and respective hypogastric artery origin as reference points. In an effort to assess the scan-to-scan variation, the distance between the SMA and lowest renal artery, which was expected to remain consistent, was measured. RESULTS: Film analysis with application of the revised migration definition confirmed fixation system failure with respect to the native arterial system in 12 (50%) of the 24 patients. Subjects judged to have endograft migration according to the reporting standards but not to have radiographic evidence of migration based on the modified criteria included 2 proximal endoleaks without evidence of device movement treated with proximal extensions, 1 procedure-related migration, 2 type III endoleaks treated with a second prosthesis implanted within the first, 1 distal endoleak treated with a limb extension, 1 rupture with presumed distal limb migration, and 2 cases of component separation. Three limb extensions were placed in the absence of leak or migration. These 12 patients all had radiographic evidence that the proximal and distal aspects of the originally implanted device did not move with respect to the native arterial vasculature, thus confirming stability of the respective fixation system. CONCLUSIONS: Adherence to this comprehensive definition of device migration, which differs from the published reporting standards, allows differentiation of the specific mechanisms of device failure. Data viewed in this context will aid in the understanding of device strengths and weaknesses, potentially improve patient assessment, and encourage design modifications to address specific aspects relating to fixation failure.     

Detection of low avidity anti-DNA antibodies in systemic lupus erythematosus.

The binding of sonicated, radiolabeled DNA by systemic lupus erythematosus (SLE) sera was measured by a high sensitivity polyethylene glycol (PEG) precipitation assay. This method is considerably more sensitive than currently used techniques. The results suggest that a significant concentration of low avidity antibodies is present in SLE sera; however, these antibodies are not detected by conventional techniques.     

Measurement of the binding of tyrosyl phosphopeptides to SH2 domains: a reappraisal.

Src homology 2 (SH2) domain-mediated interactions with phosphotyrosine residues are critical in many intracellular signal transduction pathways. Attempts to understand the determinants of specificity and selectivity of these interactions have prompted many binding studies that have used several techniques. Some discrepancies, in both the absolute and relative values of the dissociation constants for particular interactions, are apparent. To establish the correct dissociation constants and to understand the origin of these differences, we have analyzed three previously determined interactions using the techniques of surface plasmon resonance and isothermal titration calorimetry. We find that the binding of SH2 domains to phosphopeptides is weaker than generally presumed. A phosphopeptide based on the hamster polyoma middle tumor antigen interacts with the SH2 domain from Src with an equilibrium dissociation constant (Kd) of 600 nM; a phosphopeptide based on one binding site from the platelet-derived growth factor receptor binds to the N-terminal SH2 domain of the 1-phosphatidylinositol 3-kinase p85 subunit with a Kd of 300 nM; and a phosphopeptide based on the C terminus of Lck binds to the SH2 domain of Lck with a Kd of 4 microM. In addition, we demonstrate that avidity effects that result from the dimerization of glutathione S-transferase fusion proteins with SH2 domains could be responsible for overestimates of affinities for these interactions previously studied by surface plasmon resonance.     

The role of anti-DNA antibodies in lupus nephritis

Clinical Rheumatology - Anti-DNA antibodies seem to be produced as a consequence of polyclonal B cell stimulation which eventually can be skewed to anti-body formation mainly directed at nuclear...     

The binding of anti-DNA antibodies as measured fluorometrically by ethidium bromide.

The phenanthridine dye ethidium bromide (EB) intercalates with double-stranded DNA (dsDNA) resulting in an enhancement of fluorescence. Single-stranded DNA (ssDNA) does not show this fluorescent enhancement. Purified IgG from patients with Systemic Lupus Erythematosus (SLE) containing anti-dsDNA antibodies competes with EB for binding to DNA resulting in a decrease in fluorescence. This study has shown that antibodies which bind ssDNA in the Millipore filter radioimmunoassay displace EB from dsDNA showing that antigenic determinants are available for binding in the double-stranded molecule. This study introduces the EB assay and presents a comparison with the Millipore filter assay.     

The immunoglobulin class of anti-DNA antibodies: detection by a fluorometric immunoassay: clinical and pathological correlations in SLE.

The relationship of the immunoglobulin class of anti-double stranded DNA antibodies to the histological and clinical evidence of glomerulonephritis was examined in patients with systemic lupus erythematosus using a quantitative solid-phase fluorometric immunoassay. Patients with anti-DNA antibodies of the IgG class had more severe histologic changes on renal biopsy, more clinical evidence of active renal disease and lower hemolytic complement levels. The class of anti-DNA antibodies in the serum did not always correspond with the class of immunoglobulin deposited in the glomeruli of renal biopsy specimens.     

The biochemistry and genetics of DNA and anti-DNA antibodies

Clinical Rheumatology -     

小儿动脉导管未闭介入治疗随诊的超声心动图分析

目的 应用彩色多普勒超声心动图（CDFI）比较经导管五种方法堵闭小儿动脉导管未闭（PDA）的疗效。方法 1989年3月－1999年7月,超声心动图分别观察采用海绵塞（Porstman）、双面伞堵闭器（Rashkind0、纽扣式补片（Sideris）、弹簧圈闭(Coil）和蘑菇伞堵闭塞(Amplatzer）堵闭282例PDA患儿术前、术后1天、3个月、6个在动脉水平有无分流、心脏大小变化、闭器的位置及其血流动力学的改变。结果 5组患儿术后1天左室舒张末径（LVDD）和左房径（LA）明显缩小（P＜0.001）,6个月基本恢复正常;术后1天残余分流17％、3个月下降至6.4%。6个月无进一步下降。结论 Amplatzer和Coil闭法分别闭对小于或等于8.1mm和2.5mm的PDA远期疗效确切,已基本能替3代手术结扎的方法,值得在临床推广。     

Measurement of spinal mobility: a comparison of three methods.

Three techniques for measuring spinal mobility, with special reference to ankylosing spondylitis --the spondylometer, the goniometer, and a skin of distraction method--are discussed, and their accuracies and feasibilities compared. The spondylometer was found to be the quickest method, but of limited applicability to certain movements only, the goniometer the most versatile and of acceptable accuracy, and the skin distraction method inaccurate and complicated.