Functional and molecular characterization of a monoclonal antibody against human interleukin 2

Human recombinant interleukin 2 (r-IL2) was used as an immunizing antigen to yield a murine monoclonal antibody (mAb) termed BO-7. Although the antibody binds to r-IL2 more avidly, it also reacted strongly with IL2 from natural sources in an enzyme-linked immunosorbent assay (ELISA), allowing the detection of the purified lymphokine at sensitivity levels closely approaching those found with the IL2 biological assay. Binding to the antigen is specific, as deduced from the close correlation of ELISA immunoreactivity with IL2 biological activity and from immunoblot analysis of electrophoretically separated IL2 from various sources. Binding studies with synthetic IL2-derived peptides revealed the location of the epitope, which is recognized by mAb BO-7: A peptide representing amino acid residues 59-72 (peptide 84) is strongly reactive with the antibody, while an overlapping peptide (residues 48-69) is not. Peptide 84, moreover, can be applied for immunopurification of mAb BO-7 and competes for binding to the antibody with the intact IL2 molecule. In turn, another monoclonal anti-IL2 antibody (35H10), showing the same reactivity pattern with peptides, competes with mAb BO-7 for binding to IL2. The application of mAb BO-7 as a specific reagent for the quantitation of IL2 in a sandwich-type ELISA is demonstrated.     

Molecular mechanisms of anaphylaxis: lessons from studies with murine models

Studies with murine models demonstrate 2 pathways of systemic anaphylaxis: one mediated by IgE, Fc epsilonRI, mast cells, histamine, and platelet-activating factor (PAF), and the other mediated by IgG, Fc gammaRIII, macrophages, and PAF. The former pathway requires much less antibody and antigen than the latter. As a result, IgG antibody can block IgE-mediated anaphylaxis induced by small quantities of antigen without mediating Fc gammaRIII-dependent anaphylaxis. The IgE pathway is most likely responsible for most human anaphylaxis, which generally involves small amounts of antibody and antigen; similarities in the murine and human immune systems suggest that the IgG pathway might mediate disease in persons repeatedly exposed to large quantities of antigen. Mice, like human subjects, can experience IgE/Fc epsilonRI/mast cell-mediated gastrointestinal and systemic anaphylaxis in response to ingested antigen. Gastrointestinal symptoms depend on serotonin and PAF; mediator dependence of systemic symptoms has not been determined. Both local and systemic anaphylaxis induced by ingested antigens might be blocked by IgA and IgG antibodies. IL-4 and IL-13 signaling through the IL-4 receptor alpha chain, in addition to promoting the mastocytosis and IgE antibody production that mediate most human anaphylaxis, exacerbates the effector phase of anaphylaxis by increasing target cell responsiveness to vasoactive mediators. As a result, IL-4 receptor alpha chain antagonists might be particularly effective suppressors of anaphylaxis.     

Cost-effectiveness study of a lipid-lowering therapy in hyperlipoproteinaemia type IIb and type IV (Frederickson)

We performed a cost-effectiveness simulation of acipimox, bezafibrate, fenofibrate and gemfibrozil in patients with hyperlipoproteinaemia type IIb and IV (Frederickson). A distinction was made between patients with HLP type IIb and IV and HLP associated with diabetes mellitus type II (NIDDM). Direct costs were assessed as those incurred by social security for the treatment, and indirect costs were not taken into account. In appropriate dosages, all 4 substances can be considered equally efficacious in lowering lipid levels, although gallstones occur 3 times more frequently in patients treated with fibrates than in those treated with acipimox. Acquisition costs of the 4 drugs under consideration are comparable. Thus, when hospitalisation costs for treatment of gallstones are taken into account, therapy with acipimox is more cost effective than fibrate therapy.     

Sympathetic contralateral vestibulopathy after unilateral zoster oticus

A unique case of initially right sided varicella zoster induced Ramsay-Hunt syndrome with complete vestibular loss is reported. The patient subsequently developed deficits of the left vestibule 5 months later. An autoimmune pathogenesis of the left vestibular failure rather than bilateral varicella zoster infection was suggested by the following data: (1) no evidence of vesicular eruptions on the left auricle and the virtual absence of antiviral antibodies after onset of bilateral vestibulopathy; (2) prompt response of the left vestibule to immunosuppressive therapy with corticosteroids; and (3) presence of atypical nervous tissue specific autoantibodies against a 45 kDa protein.     

Neurologie 2000 Vom Molekül zum System

Ohne Zusammenfassung     

Spatiotemporal progress of nerve regeneration in a tendon autograft used for bridging a peripheral nerve defect

We have previously shown that a tendon autograft from the rat tail can support regeneration across a gap in the continuity of the rat sciatic nerve. In this study, we characterized the spatiotemporal progress of regeneration in such a graft bridging a 10-mm defect in the sciatic nerve of the rat. Regeneration was assessed 7, 10, 14, or 18 days postoperatively, by immunocytochemistry for axons, Schwann cells, and macrophages and histochemistry for blood vessels. Axonal regrowth into the grafts showed an initial delay period of 6.8 days, whereafter axons grew at a rate of 1.0 mm/day. Schwann cells grew into the grafts from both the proximal and distal nerve segments, proximally just ahead of the axonal front. Macrophages were initially preferentially located at the periphery of the grafts, but gradually increased inside the grafts. Blood vessels entered the grafts from both the proximal and distal aspects of the severed nerve. The onset of vascularization appeared to coincide with axonal regeneration into the grafts.     

Neuropsychological stability over two years in asymptomatic carriers of the Huntington's disease mutation.

This study examined whether neuropsychological changes emerge over time in asymptomatic adults who have the Huntington's disease mutation. We also evaluated whether scores on cognitive tests or psychological symptom scales varied as a function of CAG repeat length or proximity to disease onset. Twenty two healthy "mutation positive" and 37 "mutation negative" adults completed cognitive tests and psychological rating scales before disclosure of their genetic test results and on an annual basis thereafter. Repeated measures ANOVAs analysed differences between the two groups over three assessments. Correlations of cognitive and psychological symptom test scores with estimated number of years to disease onset and CAG repeat length were computed. The two groups did not differ at study entry; nor did they differ in the rate of change over time. Tests of sustained attention and mental speed correlated with estimated years to disease onset, but not with repeat length. As a group, clinically asymptomatic adults with the Huntington's disease mutation do not display neuropsychological deficits when studied over a two year interval. However, persons who are likely nearing clinical onset of Huntington's disease may develop minor deficits in selected cognitive domains before they reach threshold for diagnosis.