Production and characterization of a monoclonal antibody reactive with a specific neoantigenic determinant (comprising B beta 54-118) in degradation products of fibrin and of fibrinogen

Balb/c mice were immunized with a mixture of fibrin degradation products (XDPs) prepared by complete lysis of a human blood clot by tissue-type plasminogen activator and purified by immunoaffinity chromatography. Spleen cells of the mice were fused with P3 X 63 Ag 8653 myeloma cells. A clone (FDP 14) was selected that produces monoclonal antibodies (MoAbs) of the IgG1 kappa type that react with a neoantigenic determinant exposed in these XDPs, but not in intact fibrinogen or in fibrin monomers. Furthermore, the MoAb is reactive with some pure, individual degradation products of fibrinogen (fragments X, Y, E, and the N-terminal disulphide knot) and with the fibrinogen B beta-chain but not with A alpha- and gamma-chains or with fragments D, FCB-2 and FCB-3. Comparison of the known primary structures of these fibrinogen fragments indicates that the stretch B beta 54-118 comprises at least an important part of the epitope recognized by FDP-14. Apparently, this stretch contributes importantly to a neoantigenic determinant that is not functional in intact fibrinogen and fibrin monomer and that can be made functional by reduction of fibrinogen, or by digestion with plasmin or CNBr.     

Nasal lavage mediator profile and cellular composition of nasal brushing material during latex challenge tests

BACKGROUND: Recent studies have shown that airborne latex allergens cause allergic rhinitis and bronchial asthma. OBJECTIVE: The aim of this study was to investigate the association between the development of rhinitis reactions during workplace-related inhalative challenge tests and nasal allergic inflammation. METHODS: Thirty-two health care workers (HCWs) with suspected respiratory hypersensitivity to latex allergens underwent an inhalative workplace-related challenge test with powdered latex gloves. Nasal lavage fluid (NALF) and nasal brushing (NAB) material were collected before and after exposure (30 min, 2, 6 and 24 h) to determine mediator and cellular composition. In addition, lung function parameters and nasal flow were recorded. Furthermore, six healthy controls underwent nasal brushing and nasal lavage without latex allergen challenge at the same time intervals. RESULTS: Twenty-six HCWs showed acute rhinitis by contact to airborne latex allergen exposure and 10 of them had an additional asthma response. Only in responders, significantly increased eosinophil levels were found 6 h (P < 0.00001) and 24 h (P < 0.0005) post-challenge when compared with the prechallenge values. The ECP levels measured 2, 6 and 24 h post-challenge in the responder group were significantly elevated when compared with the prechallenge values as well as with the non-responders (6 h: P < 0.05, 24 h: P < 0.00001 afterwards). Only in some concentrated NALF samples of responders collected 30 min post-challenge (seven out of 15) tryptase concentration above the detection limit were found. The NO derivative concentrations in NALF were significantly increased 6 h post-challenge compared with the prechallenge values (P < 0.05) and were significantly higher in responders than in non-responders and in controls (P < 0.002). IL-5 levels increased post-challenge in the responder group with a pronounced effect 6 h after challenge (P < 0.001). Overall, a variety of parameters was significantly correlated (e.g. ECP with NO derivatives, r = 0.792 P < 0.002). CONCLUSIONS: Our data demonstrate for the first time that nasal and bronchial hyperreactivity to airborne latex allergens are associated with an increase of eosinophils and mediators (e.g. ECP, NO derivatives, IL-5, tryptase) in nasal mucosa. The combined use of NAB (for cells) and NALF (for mediators) appears to be a useful model to monitor nasal inflammation during workplace-related challenge tests.     

Extended naltrexone and broad spectrum treatment or motivational enhancement therapy

Background  

Randomized clinical trials on the effectiveness of naltrexone (NTX) in the treatment of alcohol dependence have produced conflicting results. One possible explanation for these discrepancies may lie in the various psychosocial treatments for which NTX is an adjunct. The goal of this study was to examine the interplay between psychosocial treatment and duration of NTX.     

Spondylometaphyseal dysplasia, corner fracture type: a heritable condition associated with coxa vara

The authors present the radiographic features of a previously incompletely delineated bone dysplasia, which they call spondylometaphyseal dysplasia, corner fracture type. This is a dominant heritable condition associated with short stature and developmental coxa vara. The progressive hip deformity usually causes significant disability requiring surgical correction. Developmental coxa vara, simulated corner fractures of long tubular bones, and vertebral body abnormalities result in a diagnostic constellation. Knowledge of these distinctive radiologic features allows accurate diagnosis, which in turn should lead to appropriate genetic counseling and possibly to earlier, more efficacious surgical treatment of the coxa vara.