A non-statistical atomic model for beam emission and motional Stark effect diagnostics in fusion plasmas.

In this work we analyze magnetic sublevel populations in a neutral beam penetrating a fusion plasma. The collisional-radiative model NOMAD was extended to include magnetic parabolic sublevels with principal quantum numbers n ≤ 10. The collisional parameters were calculated with the advanced atomic-orbital close coupling method and the Glauber approximation. The ionization by the induced electric field was also included in the model. The results of our calculations show significant deviations of the sublevel populations and, accordingly, line intensities of the σ and π components, from the statistical approximation. It is shown, for instance, that for a number of experimental conditions the total intensity of σ components is not equal to the total intensity of π components, which has a strong effect on determination of magnetic field and pitch angle in fusion devices. The results are presented for a wide range of plasma and beam parameters. The most significant deviations are observed for strong magnetic fields and high beam energies typical for the ITER plasma, where component intensity ratios may deviate by more than 20% from the statistical values.

Kidney transplantation outcomes in African-, Hispanic- and Caucasian-Americans with lupus.

African-American recipients of kidney transplants with lupus have high allograft failure risk. We studied their risk adjusting for: (1) socio-demographic factors: donor age, gender and race-ethnicity; recipient age, gender, education and insurance; donor-recipient race-ethnicity match; (2) immunologic factors: donor type, panel reactive antibodies, HLA mismatch, ABO blood type compatibility, pre-transplant dialysis, cytomegalovirus risk and delayed graft function (DGF); (3) rejection and recurrent lupus nephritis (RLN). Two thousand four hundred and six African-, 1132 Hispanic-, and 2878 Caucasian-Americans were followed for 12 years after transplantation. African- versus Hispanic- and Caucasian-Americans received more kidneys from deceased donors (71.6%, 57.3% and 55.1%) with higher two HLA loci mismatches for HLA-A (50%, 39.6% and 32.4%), HLA-B (52%, 42.8% and 35.6%) and HLA-DR (30%, 24.5% and 21.1%). They developed more DGF (19.5%, 13.6% and 13.4%). More African- versus Hispanic- and Caucasian-Americans developed rejection (41.7%, 27.6% and 35.9%) and RLN (3.2, 1.8 and 1.8%). 852 African-, 265 Hispanic-, and 747 Caucasian-Americans had allograft failure (p < 0.0001). After adjusting for transplant era, socio-demographic-immunologic differences, rejection and RLN, the increased hazard ratio for allograft failure of African- compared with Caucasian-Americans became non-significant (1.26 [95% confidence interval 0.78-2.04]). African-Americans with lupus have high prevalence of risk factors for allograft failure that can explain poor outcomes.

Review: Lupus nephritis: pathologic features, epidemiology and a guide to therapeutic decisions.

Systemic lupus erythematosus may present with renal manifestations that frequently are difficult to categorize and lupus nephritis is an important predictor of poor outcome. The type and spectrum of renal injury may remain undiagnosed until full-blown nephritic and/or nephrotic syndrome appear with increased risk of end-stage renal disease. These abnormalities occur within the first few years after the diagnosis of lupus is made on clinical grounds and with the support of laboratory tests in high risk patients. An early renal biopsy is helpful in patients with an abnormal urinalysis and/or reduced glomerular filtration rate and the results form the basis for therapeutic decisions. The biopsy also provides vital prognostic information based on histological categorization of different types of lupus nephritis, the degree of activity, chronicity and the immunopathogenesis. In the current armamentarium, the use of cyclophosphamide and azathioprine and recently mycophenolate mofetil, reduce morbidity and maintenance therapies reduce the risk of end-stage renal disease. Clinical trials underway promise new, effective and safe immunosuppressive regimens for the treatment of proliferative lupus nephritis.

Creating and manipulating vortices in atomic wave functions with short electric field pulses.

We demonstrate the creation of vortices in the electronic probability density of an atom subject to short electric field pulses, how these vortices evolve and can be manipulated by varying the applied pulses, and that they persist to macroscopic distances in the spectrum of ejected electrons. This opens the possibility to use practical femtosecond or shorter laser pulses to create and manipulate these vortex quasiparticles at the atomic scale and observe them in the laboratory. Within a hydrodynamic interpretation we also show, since the Schrödinger equation is a particular instance of the Navier-Stokes equations, that for compressible fluids vortices can appear spontaneously and with a certain time delay, which is not expected to occur from the conventional point of view, illustrating applicability of the present study to vortex formation more broadly.

Emittance characterization of a hot-cavity laser ion source at Holifield Radioactive Ion Beam Facility.

The first investigation of the transverse emittance of a hot-cavity laser ion source based on all-solid-state Ti:sapphire lasers is presented. The emittances of (63)Cu ion beams generated by three-photon resonant ionization are measured and compared with that of the (69)Ga and (39)K ion beams resulting from surface ionization in the same ion source. A self-consistent unbiased elliptical exclusion method is adapted for noise reduction and emittance analysis. Typical values of the rms and 90% fractional emittances of the Cu ion beams at 20 keV energy are found to be about 2 and 8 pi mm mrad, respectively, for the ion currents of 2-40 nA investigated. The emittances of the laser-produced Cu ion beams are smaller than those of the surface-ionized Ga and K ion beams.

Origin, evolution, and imaging of vortices in atomic processes.

Vortices are usually associated with systems containing large numbers of particles. Of particular topical interest though are those formed within atomic-scale wave functions and observed in macroscopic systems such as superfluids and quantum condensates. We uncover them here in one of the most fundamental quantum systems consisting of just one electron and two protons. Moreover, the results of novel simulations of the dynamics of this system reveal previously unknown mechanisms of angular momentum transfer and new ways to image atomic-scale quantized vortices at macroscopic distances. Probing of vortices and vortex-driven dynamics in quantum systems is thereby illustrated.

Charge transfer and ionisation by intermediate-energy heavy ions.

The use of heavy ion beams for microbeam studies of mammalian cell response leads to a need to better understand interaction cross sections for collisions of heavy ions with tissue constituents. For ion energies of a few MeV u(-1) or less, ions capture electrons from the media in which they travel and undergo subsequent interactions as partially 'dressed' ions. For example, 16 MeV fluorine ions have an equilibrium charge of 7(+), 32 MeV sulphur ions have an equilibrium charge of approximately 11(+), and as the ion energies decrease the equilibrium charge decreases dramatically. Data for interactions of partially dressed ions are extremely rare, making it difficult to estimate microscopic patterns of energy deposition leading to damage to cellular components. Such estimates, normally obtained by Monte Carlo track structure simulations, require a comprehensive database of differential and total ionisation cross sections as well as charge transfer cross sections. To provide information for track simulation, measurement of total ionisation cross sections have been initiated at East Carolina University using the recoil ion time-of-flight method that also yields cross sections for multiple ionisation processes and charge transfer cross sections; multiple ionisation is prevalent for heavy ion interactions. In addition, measurements of differential ionisation cross sections needed for Monte Carlo simulation of detailed event-by-event particle tracks are under way. Differential, total and multiple ionisation cross sections and electron capture and loss cross sections measured for C(+) ions with energies of 100 and 200 keV u(-1) are described.

State-to-state rotational transitions in H2+H2 collisions at low temperatures.

We present quantum mechanical close-coupling calculations of collisions between two hydrogen molecules over a wide range of energies, extending from the ultracold limit to the superthermal region. The two most recently published potential energy surfaces for the H(2)-H(2) complex, the so-called Diep-Johnson (DJ) [J. Chem. Phys. 112, 4465 (2000); 113, 3480 (2000)] and Boothroyd-Martin-Keogh-Peterson (BMKP) [J. Chem. Phys. 116, 666 (2002)] surfaces, are quantitatively evaluated and compared through the investigation of rotational transitions in H(2)+H(2) collisions within rigid rotor approximation. The BMKP surface is expected to be an improvement, approaching chemical accuracy, over all conformations of the potential energy surface compared to previous calculations of H(2)-H(2) interaction. We found significant differences in rotational excitation/deexcitation cross sections computed on the two surfaces in collisions between two para-H(2) molecules. The discrepancy persists over a large range of energies from the ultracold regime to thermal energies and occurs for several low-lying initial rotational levels. Good agreement is found with experiment B. Mate et al., [J. Chem. Phys. 122, 064313 (2005)] for the lowest rotational excitation process, but only with the use of the DJ potential. Rate coefficients computed with the BMKP potential are an order of magnitude smaller.

Close-coupling calculations of low-energy inelastic and elastic processes in 4He collisions with H2: A comparative study of two potential energy surfaces.

The two most recently published potential energy surfaces (PESs) for the HeH2 complex, the so-called MR (Muchnick and Russek) and BMP (Boothroyd, Martin, and Peterson) surfaces, are quantitatively evaluated and compared through the investigation of atom-diatom collision processes. The BMP surface is expected to be an improvement, approaching chemical accuracy, over all conformations of the PES compared to that of the MR surface. We found significant differences in inelastic rovibrational cross sections computed on the two surfaces for processes dominated by large changes in target rotational angular momentum. In particular, the H2(nu=1,j=0) total quenching cross section computed using the BMP potential was found to be a factor of 1000 larger than that obtained with the MR surface. A lesser discrepancy persists over a large range of energies from the ultracold to thermal and occurs for other low-lying initial rovibrational levels. The MR surface was used in previous calculations of the H2(nu=1,j=0) quenching rate coefficient and gave results in close agreement with the experimental data of Audibert et al. which were obtained for temperatures between 50 and 300 K. Examination of the rovibronic coupling matrix elements, which are obtained following a Legendre expansion of the PES, suggests that the magnitude of the anisotropy of the BMP potential is too large in the interaction region. However, cross sections for elastic and pure rotational processes obtained from the two PESs differ typically by less than a factor of 2. The small differences may be ascribed to the long-range and anharmonic components of the PESs. Exceptions occur for (nu=10,j=0) and (nu=11,j=1) where significant enhancements have been found for the low-energy quenching and elastic cross sections due to zero-energy resonances in the BMP PES which are not present in the MR potential.

Lupus nephritis: a clinical review for practicing nephrologists.

The renal manifestations in systemic lupus erythematosus (SLE) are protean and difficult to categorize into clinical syndromes and histologic classes. Lupus nephritis is frequently unrecognized until full-blown nephritic and/or nephrotic syndrome with renal failure emerge. Epidemiologically, approximately one third of SLE patients from unselected populations have renal involvement early during the disease. Most renal abnormalities emerge within the first few years of SLE diagnosis. Currently, most nephrologists agree that an early renal biopsy is worthwhile in those SLE patients with abnormal urinalysis and/or reduced renal function. First, it provides a histologic categorization of the glomerulonephritis as well as an assessment of the degree of activity and chronicity. Second, it provides vital prognostic information. Third, it is beneficial in planning a more rational therapy with or without potentially toxic immunosuppressive agents. Over the last 3 decades, many controlled clinical trials for treatment of lupus nephritis have been completed with a few therapeutic immunosuppressive regimens. Among those agents used. cyclophosphamide and azathioprine provide a reduction of morbidity in those patients afflicted with proliferative forms of lupus glomerulonephritis. A new immunosuppressive agent, mycophenolate mofetil, is being studied for treatment of proliferative forms of lupus glomerulonephritis in a controlled clinical trial at our institution. Immunosuppressive agents and the availability of dialysis and transplantation have improved the survival of patients with lupus nephritis, in particular those with proliferative forms.

Antineutrophil cytoplasmic antibodies (ANCA) and systemic vasculitis: update of assays, immunopathogenesis, controversies, and report of a novel de novo ANCA-associated vasculitis after kidney transplantation.

OBJECTIVES: To characterize antineutrophil cytoplasmic antibodies (ANCA), their major autoantigens, disease associations, and pathophysiology in systemic vasculitides. To describe a patient with a novel de novo ANCA-associated vasculitis after kidney transplantation. METHODS: We reviewed and compiled the literature on ANCA-related topics and systemic vasculitis. Laboratory and clinical data from a cadaveric kidney transplant patient who developed necrotizing vasculitis involving glomerular capillaries, with crescent formation associated with P-ANCA and myeloperoxidase, were analyzed. RESULTS: Large-scale multi-center testing of patient and normal sera by the European ANCA Assay Standardization Project using immunofluorescence assays and enzyme immunoassays indicate the assays have good sensitivity and specificity, and diagnostic utility for ANCA-associated vasculitis. A few investigations covering basic and clinical research with ANCA remain controversial: whether endothelial cells do or do not express a 29-kd neutral serine protease termed proteinase-3 (PR-3), the target of ANCA in most individuals with Wegener's granulomatosis, and whether anti-myeloperoxidase (MPO) ANCAs recognize a restricted number of epitopes on MPO. This issue has relevance for using monoclonal antibodies to treat patients with vasculitis who have adverse effects from immunosuppressive drugs. The two allelic forms of FcgammaRIIa (H131/R131) and the two of FcgammaRIIlb (NA1/NA2) are discussed as possible inheritable genetic elements for vasculitic disorders and for signaling responses. Stimulatory and costimulatory molecules, and cytokine profiles of T lymphocytes are characterized to show that these cells are actively involved in the ANCA-associated vasculitides. The patient described had a de novo ANCA associated small vessel vasculitis which developed after renal transplantation. CONCLUSIONS: There have been significant advances in the development of sensitive and specific ANCA assays. The immunopathogenetic mechanism of ANCA involves the constitutive FcgammaRs, ligands, and signaling responses to activate cytokine-primed neutrophils. This may lead to the generation of reactive oxygen intermediates, degranulation, and secretion of intracellular granule contents, and ultimately inflammation and vasculitis.

Anti-CD36 autoantibodies in thrombotic thrombocytopenic purpura and other thrombotic disorders: identification of an 85 kD form of CD36 as a target antigen.

The presence of anti-CD36 antibodies in plasma of patients with thrombotic thrombocytopenic purpura (TTP), idiopathic thrombocytopenic purpura (ITP), and heparin-induced thrombocytopenia without/with thrombosis (HIT/HITT) has been examined by immunoblots, and a monoclonal antibody capture assay, the platelet-associated IgG characterization assay (PAICA). Results with PAICA showed that 73% (8/11) of patients with TTP were positive, and 71% (10/14) by immunoblots. With ITP, 20% (6/30) were positive by PAICA and 19% (3/16) by immunoblots; HIT, 30% (3/10) were positive by PAICA and 60% (6/10) by immunoblot; HITT, 50% (2/4) by PAICA and 100% (4/4) by immunoblot. Purification of CD36 by fast protein liquid chromatography (FPLC) from Triton X-100 extracts of normal platelet membranes resulted in the isolation of two different forms: the classic 88 kD form, and a second, lighter 85 kD form. Our data indicated that the patients' plasma autoantibodies reacted strongly with the 85 kD form. Conventional monoclonal and polyclonal antisera produced to the 88 kD form reacted strongly with the 88 kD form but weakly with the 85 kD form. These results confirm the possible importance of anti-CD36 antibodies in the pathophysiology of TTP and other thrombocytopenias and demonstrate the presence of a previously unrecognized target antigen for these antibodies.

Antiphospholipid antibodies: basic immunology and assays.

Great progress has been made within the past 10 years in characterizing, assaying, and describing mechanism(s) of action in vitro of antiphospholipid antibodies (a-PL Abs); three prominent members are reagin, anticardiolipin antibodies (a-CL Abs), and the lupus anticoagulants (LAC). The major focus of this review is on basic and current biochemical and immunologic research. First, the biochemistry, structural composition, and sources of anionic and dipolar ionic (zwitterionic) phospholipids are discussed together with several serum antibodies directed to these phospholipids. Cardiolipin, the most acidic phospholipid (net negative charge of 2 at pH 7.0) has been historically important as an antigen for testing reagin in syphilis serology, and currently is part of the antigenic composition used in the Venereal Disease Research Laboratory (VDRL) tests. In this connection, the chronic biological false-positive test for syphilis and the LAC are discussed in association with autoimmune disorders such as systemic lupus erythematosus. Second, a naturally occurring plasma anticoagulant in vitro and a critical cofactor for binding of purified autoimmune a-CL Abs to cardiolipin is considered, the beta 2-glycoprotein I (beta 2-gpI). This single-chain plasma polypeptide is highly glycosylated, has 326 amino acids, a molecular weight of 50 kD, and is characterized by repeating amino acid motifs or domains that structurally resemble multiple loops. The highly cationic C-terminal fifth domain binds to anionic phospholipids. The beta 2-gpI is a member of the short consensus repeat superfamily of proteins, and is compared with other proteins with similar domains. Third, experiments are detailed for defining LAC and distinguishing it from other a-CL Abs. Cofactors are also associated with LAC and include beta 2-gpI, prothrombin, protein C, protein S, tissue factor, and factor XI. Thus, LAC antibodies are heterogeneous, and no individual assay can detect all LACs. Because patients with syphilis and other infectious diseases have no cofactor associated with a-CL Abs, their plasma LACs are negative. The a-CL Abs found in infection are not associated with the clinical features of the antiphospholipid syndrome. LAC assays are important because of the pathogenetic association with clinical observations of venous and arterial thrombosis, thrombocytopenia, and recurrent fetal loss. Finally, reports leading to development of currently used direct solid-phase enzyme-linked immunosorbent assays (ELISA) for testing a-PL Abs are outlined; these developments have greatly increased understanding of the basic immunology of target antigens and their respective antibodies. Of significance, a-CL Abs cross-react with other anionic phospholipids. Additionally, the results of these assays led to the realization that high levels of circulating a-PL Abs over long periods are associated with a number of clinical problems now known collectively as the antiphospholipid syndrome.

Antibody-independent binding of complement component C1q by Legionella pneumophila.

Incubation of Legionella pneumophila Philadelphia 1 in normal human serum depleted of either classical-pathway component C1q or alternative-pathway component factor B resulted in activation of the complement system. Experiments focused on the role of the classical pathway in complement activation revealed that legionellae bound C1q independently of antibody. Purified preparations of L. pneumophila major outer membrane protein but not serogroup 1 lipopolysaccharide bound C1q independently of antibody. This suggests that antibody-independent binding of C1q by L. pneumophila can result in activation of the classical pathway in normal human serum and that major outer membrane protein may be a C1q acceptor on the L. pneumophila cell surface.

Antineutrophil cytoplasmic antibodies: major autoantigens, pathophysiology, and disease associations.

Antineutrophil cytoplasmic antibodies (ANCA) are important serological markers for the primary systemic vasculitides, including microscopic polyarteritis and necrotizing crescentic glomerulonephritis. Numerous reports have established the clinical utility of ANCA titer in monitoring disease activity, relapses, and response to treatment. ANCA, detected by indirect immunofluorescence (IIF) assays using patient's serum and ethanol-fixed human neutrophils, produce two common fluorescent staining patterns: cytoplasmic (C-ANCA), involving a 29-kD neutral serine protease termed proteinase 3 (PR3), and perinuclear (P-ANCA), the result mainly of myeloperoxidase (MPO), but occasionally by other components of the azurophilic granules including lysozyme, elastase, cathepsins, and lactoferrin. Some sera contain granulocyte-specific antinuclear antibodies (GS-ANA), which require formaldehyde fixation of neutrophils to cross link cytoplasmic antigens for distinguishing between ANCA and the GS-ANA by IIF. Positive IIF is confirmed by Western blot analysis or specific enzyme-linked immunosorbent assay for PR3, MPO, and other neutrophil granule antigens. The C-ANCA pattern is highly specific for Wegener's granulomatosis, a disease characterized by granulomatous inflammation, necrotizing and crescentic glomerulonephritis, and vasculitis; P-ANCA is found in sera of individuals with vasculitis, glomerulonephritis, and several other diseases. ANCA are predominantly immunoglobulin (Ig)G isotype, but may be IgM and IgA. Various pathophysiologic mechanisms have been proposed involving ANCA-mediated neutrophil activation in a hypothetical model of vasculitic diseases: positive signals via the FcgammaRII (CD32) receptor after IgG-ANCA binding to membrane-associated PR3, relevant cytokines, production of adhesion molecules on both activated neutrophils and endothelial cells, and the release of neutrophil reactive oxygen species and degranulation causing endothelial cell damage. Interference of C-ANCA with PR3 proteolysis and PR3 inhibition physiologically by the alpha1-proteinase inhibitor may have a pathogenic role. No convincing data have been reported for the existence of autoreactive T lymphocytes reactive to any degree with the neutrophil azurophilic enzymes. Studies of various drug- and infectious agent-related diseases and ANCA may contribute to understanding the mechanism(s) involved in some vasculitides.

M proteins of group G streptococci: mechanisms of resistance to phagocytosis.

Group G streptococci that express M protein and resist phagocytosis in human blood (virulent strains) were compared with strains of groups G and A that are readily phagocytosed (avirulent). Virulent group G streptococci were less effective (P < .05) as activators of the alternative complement pathway (ACP) than were avirulent streptococci. In immunofluorescence studies, C3 bound more avidly to avirulent than to virulent group G streptococci. Resistance of virulent group G strains to ACP opsonization and to phagocytosis was markedly diminished by removal with pepsin of the type-specific portion of the M molecule. Preincubation with fibrinogen did not diminish ACP activation or C3 binding by virulent group G and A streptococci but did exert an antiphagocytic effect. Given the similarity of M proteins of groups G and A in structure and function, other microbial constituents are likely responsible for differences in the spectra of illnesses attributable to the two serogroups.

Modified immunoassays for polyether toxins: implications of biological matrixes, metabolic states, and epitope recognition.

Polyether marine toxins are responsible for the seafood intoxication phenomena known as neurotoxic shellfish poisoning (due to brevetoxins), ciguatera (due to ciguatoxin), and diarrheic shellfish poisoning (due to okadaic acid). Using traditional techniques of hapten (pure toxin) conjugation to protein to create complete antigen, animal immunization and antibody isolation, and specific antibody subpopulation purification, discriminating antibodies have been isolated that detect brevetoxins and ciguatoxin, but not okadaic acid, in a dose-dependent fashion. Using microorganic chemistry and purified toxins, a unique set of tools has been created for the study of polyether ladder toxin accumulation; depuration; and specific site localization in tissues, food sources, and clinical samples. Developed test protocols can detect toxin in dinoflagellate cells, in extracts from food sources, in seawater and culture media, and in human serum samples. Enzyme-linked immunosorbent assay protocols developed for eventual collaborative testing have been successful in limited applications within the laboratory (correlation coefficient of 0.92 excluding 2 outliers), and alternative formats are being developed to optimize the basic test for use in research laboratories, regulatory laboratories, and field inspections.

Brevetoxin PbTx-2 immunology: differential epitope recognition by antibodies from two goats.

The epitopic regions of the brevetoxin PbTx-3 molecule, produced by the marine dinoflagellate Ptychodiscus brevis, have been identified by structural modification at three distinct regions of the toxin. These are: the A-ring lactone region of the molecule, the K-ring side-chain and the H-ring. The modified PbTx-3 derivatives were tested for their ability to bind brevetoxin goat antisera directed against the PbTx-3 molecule, by radioimmunoassay. The results showed that at least two major epitopes and one minor epitope are recognized: the A-ring lactone region of the molecule and the K-ring side-chain, and the H-ring. The results illustrate the variety of antibodies which may be produced, even within a species, and suggests that epitope characterization is important in the development of assays which are to be employed in seafood safety issues.

Complement-mediated fragmentation and lysis of opsonized platelets: ender differences in sensitivity.

It was reported that elevated levels of platelet microparticles (PMPs) in patients with immune thrombocytopenic purpura (ITP) were associated with decreased bleeding, and in some cases with small vessel thromboses (J Lab Clin Med 1992; 119:334). To investigate the possible role of complement in PMP production in ITP, an in vitro assay was developed to simulate ITP: platelets were opsonized with well-defined monoclonal antibodies against glycoprotein IIb/IIIa, of immunoglobulin G (alpha-CD41), and of immunoglobulin M (alpha-Plt-1) class, then exposed to serum as a source of complement. PMP generation and lysis were monitored by flow cytometer, by release of lactic dehydrogenase, and by generation of procoagulant activity. These effects were largely abolished by heating the serum (30 minutes, 65 degrees) or by incubation with alpha-C1q, confirming the role of complement. At low concentrations of serum, both monoclonal antibodies promoted PMP shedding in a concentration-dependent manner without loss of platelet population; at higher concentrations, extensive lysis occurred, but marked variations in resistance to lysis were observed in platelets from different individuals. The PMPs produced were associated with increased procoagulant activity, as measured by the Russell's viper venom test. The immunoglobulin M antibody was more potent than the immunoglobulin G antibody in promoting lysis, and the resulting PMPs had greater procoagulant activity. To clarify the variation seen in platelets from different donors, data was sorted on the basis of gender, with the finding that women's platelets are significantly more sensitive to complement-mediated damage than men's. This may explain in part why ITP is three to four times more prevalent in women than in men. We conclude that complement activation is the most likely explanation for the elevated level of PMPs often seen in patients with ITP and sometimes associated with thrombosis and that the determining factors are the concentration and nature of antibody as well as individual differences in sensitivity to complement-mediated damage. Because complement activation can occur without participation of antibody, complement activation may also be the cause of elevated PMP levels seen in other thrombotic disorders not involving platelet-specific antibodies.