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  • 1
    Electronic Resource
    Electronic Resource
    Factor VIII immunogenicity (1998)
    Oxford, UK : Blackwell Science Ltd
    Haemophilia 4 (1998), S. 0 
    Details
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary. The immunogenicity of factor VIII depends on the interaction of multiple parametres including host susceptibility and characteristics of the factor VIII preparations. We briefly review here the basic mechanisms by which tolerance to self is established, maintained, and possibly broken in the context of haemophilia A, with special emphasis on the severity of the disease. Reference is also made to the situation observed in healthy individuals and patients with autoantibodies to factor VIII.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2516.1998.440552.x
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  • 2
    Electronic Resource
    Electronic Resource
    Inhibitors in haemophilia: pathophysiology (2004)
    Oxford, UK : Blackwell Publishing Ltd
    Haemophilia 10 (2004), S. 0 
    Details
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary.  Development of inhibitors to coagulation factors is one of the major problems faced by people with haemophilia. Up to a third of patients, following treatment with factor concentrates, will develop an antibody (inhibitor) to that factor, rendering it inactive, and leaving the patient at risk from life-threatening bleeding. Evidence shows that this immune response is T-cell-dependent, but as yet, the epitopes responsible have not been identified. Risk for inhibitor development is highest within the first 50 days of treatment, with reactions being rare after 200 days. The risk is mediated by the major histocompatibility complex class of the patient, and by mutations in the factor VIII genotype, with large deletions conferring greatest risk.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2516.2004.01009.x
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  • 3
    Electronic Resource
    Electronic Resource
    New high-technology products for the treatment of haemophilia (2004)
    Oxford, UK : Blackwell Publishing Ltd
    Haemophilia 10 (2004), S. 0 
    Details
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary.  This review will focus on new technologies in development that promise to lead to further advances in haemophilia therapeutics. There has been continued interest in the bioengineering of recombinant factor VIII (rFVIII) and factor IX (rFIX) with improved function to overcome some of the limitations in current treatment, the high costs of therapy and to increase availability to a broader world haemophilia population. Bioengineered forms of rFVIII, rFIX or alternative haemostatic molecules may ultimately have an impact on improving the efficacy of therapeutic strategies for the haemophilias by improving biosynthesis and secretion, functional activity, half-life and immunogenicity. Preventing and suppressing inhibitors to factor (F) VIII remain a challenge for both clinicians and scientists. Recent experiments have shown that it is possible to obtain anti-idiotypic antibodies with a number of desirable properties: (i) strong binding avidity to FVIII inhibitors; (ii) neutralization of inhibitory activity both in vitro and in vivo; (iii) cross-reactivity with antibodies from unrelated patients, and (iv) no interference with FVIII function. An alternative, although complementary approach, makes use of peptides derived from filamentous-phage random libraries. Mimotopes of FVIII can be obtained, which bind to the paratope of inhibitory activity and neutralize their activity both in vitro and in vivo. In this paper, we review advanced genetic strategies for haemophilia therapy. Until recently the traditional concept for gene transfer of inherited and acquired haematological diseases has been focused on how best to obtain stable insertion of a cDNA into a target-cell genome, allowing expression of a therapeutic protein. However, as gene-transfer vector systems continue to improve, the requirement for regulated gene transcription and hence regulated protein expression will become more critical. Inappropriate protein expression levels or expression of transferred cDNAs in non-intended cell types or tissues may lead to target-cell toxicity or activation of unwanted host immune responses. Regulated protein expression requires that the transferred gene be transferred with its own regulatory cassette that allows for gene transcription and translation approaching that of the normal gene in its endogenous context. New molecular techniques, in particular the use of RNA molecules, now allow for transcription of corrective genes that mimic the normal state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2516.2004.00996.x
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  • 4
    Electronic Resource
    Electronic Resource
    Human auto-anti-idiotypic antibodies to mite-specific IgE can degranulate human basophils in vitro (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 25 (1995), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Anti-idiotypic antibodies (anti-Ids) to specific IgE antibodies are formed spontaneously during an anti-allergen immune response and can be induced by immunotherapy. Although anti-Ids can down-regulate the production of IgF. antibodies, at least in experimental models, their possible role in the modulation of target cell reactivity remains ill-defined.Objective The capacity of human anti-Ids to modulate the release of histamine was examined in an in vitro system of human basophil degranillation. Anti-Ids were prepared from the serum of six Dermatophagoides pteranyssinus (DP)-hypersensitive patients suffering from atopic dermatitis and who had never been desensitized. Basophils were obtained from the blood of atopic donors. The extent of histaminc release was determined using a fluorometric assay.Results We show that: anti-Ids trigger the release of histamine in an allergen-specific, dose- and IgE-dependent manner; the release is not due to the presence of allergen and/ or anti-IgE antibodies: and that the degranulating activity can be removed by absorption with affinity-purified anti-Dp antibodies of the corresponding patient.Conclusion These results indicate that spontaneously produced human anti-Ids can modulate the reactivity of human basophils.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1995.tb00395.x
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  • 5
    Electronic Resource
    Electronic Resource
    Complexes of grass pollen allergens and specific antibodies reduce allergic symptoms and inhibit the seasonal increase of IgE antibody (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 20 (1990), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Complexes made from antigen and specific antibodies have been used to suppress specific antibody production. This property is of potential therapeutic interest in immediate hypersensitivily states which are characterized by hyperproduction of IgE antibodies. We report here on the use of antigen-antibody complexes in patients with hypersensitivity to grass pollen. Specific anti-allergen antibodies were prepared by immunoadsorption from the serum of hypersensitive individuals and mixed with grass pollen allergens to form complexes in antibody excess. These complexes were used in a strictly autologous manner for inoculating patients prior to and during a pollen season. The study comprised two randomly defined groups of 15 patients who were inoculated intradermally either with a preparation of allergen-antibody complexes or with the carrier buffer, according to a double-blind protocol. Diary cards were used to follow nasal and ocular symptoms, bronchial asthma and medication intake. Specific IgE antibodies were assayed during the trial and 1 year afterwards.Inoculation of allergen-autologous antibody complexes was well tolerated. It significantly reduced ocular symptoms (Mann-Whitney U-test, P 〈 0·05), bronchial asthma during the first part of the season (Mann-Whitney U-test, P 〈 0·001) and drug intake (Mann-Whitney U-test, P 〈 0·001). This treatment prevented the seasonal increase in specific IgE antibodies, whose production continued to decrease after the pollen season. These effects were obtained within a few weeks of treatment, using a cumulative amount of allergen 100-fold lower than the amount which would have been used for a conventional hyposensitization.Inoculation of allergen-antibody complexes might prove to be a valuable alternative for the treatment of immediate hypersensitivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1990.tb02704.x
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  • 6
    Electronic Resource
    Electronic Resource
    Uptake of exogenous ribonucleic acid by ascites tumor cells - I. Autoradiographic and chromatographic studies
    Amsterdam : Elsevier
    Experimental Cell Research 43 (1966), S. 381-390 
    Details
    ISSN: 0014-4827
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0014-4827(66)90065-6
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  • 7
    Electronic Resource
    Electronic Resource
    New fluoroketones as human renin inhibitors
    Amsterdam : Elsevier
    FEBS Letters 249 (1989), S. 47-50 
    Details
    ISSN: 0014-5793
    Keywords: Enzyme inhibitor ; Fluoroketone ; Renin ; Retroamide bond
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0014-5793(89)80012-2
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  • 8
    Electronic Resource
    Electronic Resource
    Radiosensitivity of swine lymphocytes: in vitro modification of the cell cycle and kinetics of the appearance of chromosomal aberrations
    Amsterdam : Elsevier
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 126 (1984), S. 169-175 
    Details
    ISSN: 0027-5107
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0027-5107(84)90059-9
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  • 9
    Electronic Resource
    Electronic Resource
    Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinius (1988)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 43 (1988), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Specific antibodies isolated by immunoabsorption on four main insolubilized allergens from Dermatophagoides pteronyssinus (DPT) had the following isotypic distribution: in 16 atopic patients, 52% IgG, 40% IgM, 8% IgA, 0.1% IgE and, in 12 non-atopic individuals, 48% IgG, 46% IgM, 6% IgA, 0.03% IgE. The ratios between geometric means of antibody values in each class (atopic vs non-atopies) were 2.4 for IgG, 2.0 for IgM, 2.8 for IgA and 66.7 for IgE. The amount of anti-DPT antibodies in IgG subclasses (did not follow the usual distribution of total IgG subclasses, i.e., IgG1 〉 lgG2 〉 IgG3 〉 IgG4. In atopies the order was IgG2 〉 IgG1 〉 IgG4 〉 lgG3 and in non-atopies, IgG4 〉 IgGl - IgG2 〉 IgG3 although 6/12 of the latter had no detectable (〈 0.5 μg/ml plasma) IgG4.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1988.tb00427.x
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  • 10
    Electronic Resource
    Electronic Resource
    Allergen-antibody complexes can efficiently prevent seasonal rhinitis and asthma in grass pollen, hypersensitive patients (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 46 (1991), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have prepared antigen-antibody complexes from grass pollen allergens and autologous specific antibodies isolated by immunoadsorption from the serum of allergic patients. These Complexes were inoculated into patients in a double-blind trial to evaluate their effect on grass pollen-related rhinitis and bronchial asthma. Thirty-eight grass pollen-hypersensitive patients were allocated to three groups; patients in the first two groups were treated with antigen-antibody complexes at different ratios and dosages and were compared with the third group who received the placebo carrier buffer alone. In addition, we treated a fourth group who had already received antigen-antibody complex inoculation during the previous pollen season. Injections were given every 2 weeks during the pollen season, starting 5 weeks prior to it. Tolerance was excellent with no signs of local or systemic side effects. The treatment prevented nasal symptoms while enabling the patients to reduce antihistamine intake. Bronchial asthma was virtually absent in the treated groups even though no bronchodilators or corticosteroids had to be taken. Specific IgE antibodies did not increase during the pollen season nor did IgG “blocking” antibodies. Inoculation of allergen-antibody complexes could provide a valuable alternative for the treatment of immediate hypersensitivity to airborne allergens as it appears to be safe and rapidly efficacious. This treatment offers several advantages compared to conventional hyposensitization and is characterized by the absence of an increase in specific IgG antibodies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1991.tb00596.x
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