Dimeric IVIG contains natural anti-Siglec-9 autoantibodies and their anti-idiotypes.

BACKGROUND: Intravenous immunoglobulin (IVIG) preparations are increasingly used for the treatment of autoimmune and chronic inflammatory diseases. Naturally occurring autoantibodies against Siglec-9 and Fas are thought to contribute to the anti-inflammatory effects of IVIG via cell death regulation of leukocytes and tissue cells. Dimeric IVIG fractions are suspected to contain idiotypic (Id)-anti-idiotypic complexes of antibodies, which might also include anti-Siglec-9 and anti-Fas autoantibodies. METHODS: Dimeric IVIG fractions were separated from monomeric IVIG by size-exclusion chromatography and remonomerized by low pH treatment. Binding studies of total, monomeric, and dimeric IVIG were performed using surface plasmon resonance and flow cytometry on primary human neutrophils. RESULTS: Anti-Siglec-9 and anti-Fas autoantibodies were contained in both monomeric and dimeric IVIG fractions, but anti-Siglec-9 antibodies were highly enriched in dimeric IVIG. The propensity to engage in dimer formation was paratope dependent. IVIG binding to Siglec-9 was specific and sialylation independent. Interestingly, we detected anti-idiotypic antibodies (anti-Ids) against anti-Siglec-9 autoantibodies in dimeric, but not in monomeric fractions of IVIG. CONCLUSIONS: Our study supports the concept that idiotype-anti-idiotype (Id-anti-Id) interactions contribute to the dimer formation in IVIG preparations. To our knowledge, this is the first description of Id-anti-Id dimers of death receptor-specific antibodies in IVIG. Such Id-anti-Id interactions might determine the activity of immunomodulatory antibodies present both in IVIG and the patient.

Enfermedad injerto contra huésped crónica / Chronic graft versus host disease

Antecedentes: La enfermedad injerto contra huésped (EIVH) se produce cuando las células inmunocompetentes del donante generan una reacción inflamatoria contra un tejido del huésped inmunodeprimido, la cual compromete la piel, el hígado, la mucosa oral y ocular, y el tracto gastrointestinal. En la piel las manifestaciones son múltiples, secuenciales e indicadoras del pronóstico de la enfermedad. Objetivo: presentar la evolución clínica completa, durante dos años de control evolutivo, de una enfermedad injerto contra huésped crónica desarrollada en una paciente de sexo masculino, de 17 años, con trasplante de médula ósea (stem cells) alogénico periférico, HLA idéntico emparentado (hermana), para que las lesiones sean reconocidas y diagnosticadas por los dermatólogos. Diseño: se registraron día a día, durante dos años, todas las manifestaciones dermatológicas que fueron surgiendo a lo largo del tiempo, como también las transformaciones de las lesiones típicas de la fase temprana o liquenoide de la enfermedad, en lesiones esclerodermiformes características de la fase tardía.Materiales y métodos: las lesiones fueron confirmadas con estudios histopatológicos. Se realizaron exámenes complementarios específicos que demostraron el compromiso sistemático en el paciente. Resultados: se registró la evolución completa de una enfermedad injerto contra huésped crónica; se confirmó afección en la piel, hepática, ocular y de la mucosa oral. Conclusiones: destacamos la importancia para los médicos dermatólogos de conocer las múltiples manifestaciones cutáneas en las distintas etapas de la enfermedad injerto contra huésped crónica, ya que sus manifestaciones en piel son prioritarias e indicadoras del pronóstico de la enfermedad

Enfermedad injerto contra huésped crónica / Chronic graft versus host disease

Antecedentes: La enfermedad injerto contra huésped (EIVH) se produce cuando las células inmunocompetentes del donante generan una reacción inflamatoria contra un tejido del huésped inmunodeprimido, la cual compromete la piel, el hígado, la mucosa oral y ocular, y el tracto gastrointestinal. En la piel las manifestaciones son múltiples, secuenciales e indicadoras del pronóstico de la enfermedad. Objetivo: presentar la evolución clínica completa, durante dos años de control evolutivo, de una enfermedad injerto contra huésped crónica desarrollada en una paciente de sexo masculino, de 17 años, con trasplante de médula ósea (stem cells) alogénico periférico, HLA idéntico emparentado (hermana), para que las lesiones sean reconocidas y diagnosticadas por los dermatólogos. Diseño: se registraron día a día, durante dos años, todas las manifestaciones dermatológicas que fueron surgiendo a lo largo del tiempo, como también las transformaciones de las lesiones típicas de la fase temprana o liquenoide de la enfermedad, en lesiones esclerodermiformes características de la fase tardía.Materiales y métodos: las lesiones fueron confirmadas con estudios histopatológicos. Se realizaron exámenes complementarios específicos que demostraron el compromiso sistemático en el paciente. Resultados: se registró la evolución completa de una enfermedad injerto contra huésped crónica; se confirmó afección en la piel, hepática, ocular y de la mucosa oral. Conclusiones: destacamos la importancia para los médicos dermatólogos de conocer las múltiples manifestaciones cutáneas en las distintas etapas de la enfermedad injerto contra huésped crónica, ya que sus manifestaciones en piel son prioritarias e indicadoras del pronóstico de la enfermedad (AU)

Reduced protein adsorption and platelet adhesion by controlled variation of oligomaltose surfactant polymer coatings.

A series of oligomaltose surfactant polymers were prepared by the simultaneous coupling of hydrophilic maltolactone [of 2(M2), 7(M7), or 15(M15) glucose units] and hydrophobic N-(hexanoyloxy)succinimide (Hex) groups to the amino groups of a poly(vinyl amine) backbone. The surfactants were characterized by FTIR and 1H-NMR spectroscopies for purity and composition. Contact-angle and AFM measurements confirmed full monolayer adsorption for all surfactants on a model surface, highly oriented pyrolitic graphite, while full coverage was observed on polyethylene only for PVAm (M7:Hex) due to the optimal M7:Hex ratio and Hex chain density. On graphite, protein resistance increased with increasing coating thickness from 81.4 to 85.8 to 95.8% for the M2, M7, and M15 surfactants, respectively. Additionally, static platelet adhesion on all three surfactants dropped substantially to 15% (M2), 17% (M7), and 16% (M15)compared to glass (adhesion normalized to 100%) and a polyurethane (24%) surface. Protein- and platelet-resistant properties of the controlled oligomaltose layers are discussed by analysis of molecular modeling, oligomaltose and hexanoyl chain densities, and surfactant stability.

Biomimetic engineering of non-adhesive glycocalyx-like surfaces using oligosaccharide surfactant polymers.

The external region of a cell membrane, known as the glycocalyx, is dominated by glycosylated molecules, which direct specific interactions such as cell-cell recognition and contribute to the steric repulsion that prevents undesirable non-specific adhesion of other molecules and cells. Mimicking the non-adhesive properties of a glycocalyx provides a potential solution to the clinical problems, such as thrombosis, that are associated with implantable devices owing to non-specific adsorption of plasma proteins. Here we describe a biomimetic surface modification of graphite using oligosaccharide surfactant polymers, which, like a glycocalyx, provides a dense and confluent layer of oligosaccharides. The surfactant polymers consist of a flexible poly(vinyl amine) with dextran and alkanoyl side chains. We show that alkanoyl side chains assemble on graphite through hydrophobic interaction and epitaxial adsorption. This constrains the polymer backbone to lie parallel to the substrate, with solvated dextran side chains protruding into the aqueous phase, creating a glycocalyx-like coating. The resulting biomimetic surface is effective in suppressing protein adsorption from human plasma protein solution.

Surface Activity of ABA-Type Nonionic Oligosaccharide Surfactants

We report on the surface activity of two novel ABA-type nonionic oligosaccharide surfactants: N,N '-dodecamethylene-bismaltonamide and N,N '-dodecamethylene-bis(dextran aldonamide) (DEX-C12-DEX). Surface active properties, determined from surface tension measurements, were compared with results for AB-type counterparts containing the same hydrophobic segment, N -dodecylmaltonamide and N -dodecyl dextran aldonamide (DEX-C12). Surface tension measurements, including analysis of binary surfactant mixtures of DEX-C12 and DEX-C12-DEX show that the DEX-C12-DEX does not form micelles, but induces micelle formation of DEX-C12 at a critical total surfactant concentration and diblock mole fraction. We show the effects of oligosaccharide chain length and molecular geometry on surface activity and packing density and, with the aid of molecular models, discuss our results from the viewpoint of surfactant conformation.

Visualization of dipole solutions to the neuromagnetic inverse problem.

We have developed a computer program that computes and displays current-dipole solutions to the neuromagnetic inverse problem. The three-dimensional positions, orientations, and corresponding magnetic field values of the detection coils can be visualized with respect to a realistic representation of the subject's head shape. The topographies of the experimental data, theoretical fit, and residual field are represented without the use of data smoothing or interpolation, allowing more direct comparisons between them. A simple method for displaying dipole source location was implemented.

[Diagnosis of acute and chronic injuries of the knee joint]. / Diagnostik frischer und chronischer Kniegelenkverletzungen.

Following a general review of the basic principles of knee examination, the specific instability tests of the different ligaments are explained. The pathophysiology, the pathomechanic and the diagnostic evidence of these instability tests are shown. The diagnosis of meniscal and cartilaginous lesions are not discussed.

[Therapy of posterior and posterolateral knee instability]. / Therapie der posterioren und posterolateralen Knieinstabilität.

The natural course after posterior cruciate ligament (PCL) tear is a slow process of degeneration starting in the medial compartment. Functional disability is mainly present in those instabilities that are combined with posterolateral insufficiency. The surgical treatment at present mainly addresses these combined types of posterior-posterolateral instability. It is generally agreed that suture of the torn PCL alone is insufficient and augmentation with autologous structures, such as the patellar ligament, are mandatory. Synthetic augmentation to facilitate after treatment is another adjunct. Because of the difficulty of precise tibial tunnel placement a two-stage procedure is advocated, an anterior approach with the patient supine being used for femoral graft placement. If a posterior approach with the patient prone is used, a straight posterior incision is made between the two heads of the gastrocnemius and the neuromuscular bundle. With this approach the tibial bone block is placed in a trough. The accuracy of graft placement and the immediate functional aftertreatment facilitated by the use of osseous fixation of a synthetic augmentation device at both ends have made better results of surgical reconstruction of the PCL possible.

Spatiotemporal visualization of neuromagnetic data.

We describe the development of a computer visualization tool that displays topographic maps of neuromagnetic data on realistic head shapes. Two topographic display modes are implemented--a raw mode that depicts the actual position, orientation, and corresponding magnetic field data of each detection coil with respect to the head shape, and an interpolated mode, where the magnetic data are smoothly interpolated over the scalp. False coloration is used to represent magnetic field strength. The topographic displays are coupled with wave form displays in order to integrate spatial and temporal visualization of the data. The X Window system is used to write device independent, network-transparent computer code.

The dose-dependent systemic availability of prednisone: one reason for the reduced biological effect of alternate-day prednisone.

An analysis of the literature was performed, revealing that in many studies both the desired and the undesired effects are decreased in alternate-day prednisone regimens as compared with the daily regimens. In the present report evidence is given that part of the diminished biological effect of dose-spacing regimens is attributable to a decreased total exposure to prednisolone. Following a high dose of 0.8 mg kg-1 of oral prednisone or prednisolone the plasma concentration vs time curves of total prednisolone, unbound prednisolone and prednisolone bound to albumin or transcortin were always less than four times higher than following a low dose of 0.2 mg kg-1 of prednisone or prednisolone. This dose-dependent systemic availability of prednisolone explains partly the diminished biological effect when the same total amount of prednisone or prednisolone is divided into several small doses as opposed to a single oral dose.