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  • 1
    Electronic Resource
    Electronic Resource
    Favourable interaction between heavy and light chains arrests the undesirable oligomerization of heavy chains in the refolding of denatured and reduced immunoglobulin G (1997)
    Springer
    Cellular and molecular life sciences 53 (1997), S. 929-934 
    Details
    ISSN: 1420-9071
    Keywords: Key words. Aggregation; H chain; immunoglobulin G; L chain; protein folding; slow dialysis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Recently we developed a slow dialysis method that effectively refolds denatured and reduced immunoglobulin G (IgG) [Maeda, Ueda and Imoto (1996) Prot. Engng 9: 95-100]. This method allows both individual and simultaneous refolding of denatured and reduced H and L chains. Analysis by SDS-polyacrylamide gel electrophoresis revealed that some oligomers were formed through disulfide bonds when H chains were refolded individually. It was also shown that the extent of IgG obtained by rejoining the mixture of refolded H and L chains which had been refolded individually was similar to that obtained by refolding denatured and reduced whole IgG. The results indicated that a favourable interaction between H and L chains prevented formation of H-chain oligomers to yield intact IgG. The present results suggest a mechanism whereby individually folded chains might associate to form IgG molecules in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000180050113
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  • 2
    Electronic Resource
    Electronic Resource
    The safety of pegylated interferon alpha-2b in the treatment of chronic hepatitis B: predictive factors for dose reduction and treatment discontinuation (2005)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 21 (2005), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Treatment with interferon-alpha has been shown to be effective in one-third of hepatitis B e antigen-positive chronic hepatitis B patients, but is clinically associated with relevant adverse events.Aim : To investigate the safety of pegylated interferon alpha-2b in 300 hepatitis B e antigen-positive patients with compensated liver disease.Methods : Patients were treated with pegylated interferon alpha-2b for 52 weeks combined with either lamivudine 100 mg/day or placebo. Pegylated interferon alpha-2b was administered for 100 μg once a week for 32 weeks; thereafter, the dose was reduced to 50 μg once a week. Adverse events and their effect on study medication were reported at monthly visits in a standardized way.Results : The most frequently reported side-effects were flu-like syndrome (68%), headache (40%), fatigue (39%), myalgia (29%) and local reaction at the injection site (29%). These symptoms typically occurred within the first month of therapy and subsided during the course of therapy. Neutropenia and thrombocytopenia induced by pegylated interferon alpha-2b increased the risk of infections and bleeding complications, but these complications were rare and mild. The frequency of all side-effects was not different between patients treated with pegylated interferon alpha-2b combined with lamivudine or placebo. In 69 (22%) patients the dose of pegylated interferon alpha-2b was reduced prematurely. Of these dose reductions, 36 (52%) were because of neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent reasons for early discontinuation were psychiatric side-effects (depression, psychosis) and flu-like symptoms. Multivariate Cox regression analysis showed that low neutrophil count at baseline and cirrhosis were independent predictors of dose reduction or therapy discontinuation.Conclusion : We conclude that in patients with chronic hepatitis B and compensated liver disease prolonged pegylated interferon alpha-2b therapy is safe, and that pre-existent cirrhosis and neutropenia are the most important predictors of dose reduction or early treatment discontinuation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.2005.02453.x
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  • 3
    Electronic Resource
    Electronic Resource
    Interleukin-12 enhances the antitumor activity of cytotoxic T lymphocytes against lung adenocarcinoma engrafted in severe combined immunodeficient mice (2000)
    Springer
    International journal of clinical oncology 5 (2000), S. 262-268 
    Details
    ISSN: 1437-7772
    Keywords: Key words Interleukin-12 ; SCID mouse ; Adoptive immunotherapy ; Cytotoxic T lymphocyte ; Lung cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Through a number of biologic activities, interleukin 12 (IL-12) has proven to be a potential antitumor cytokine in mice bearing a variety of malignancies. However, in clinical trials in humans, the eradication of solid tumors remains difficult. Methods. A lung cancer cell line (PC-9)-specific cytotoxic T lymphocytes (CTL) were generated by multiple stimulations, with irradiated PC-9 cells, of regional lymph node lymphocytes obtained from patients with lung cancer whose cells expressed the same HLA-A locus haplotype as PC-9 (HLA-A24). Severe combined immunodeficient (SCID) mice bearing a subcutaneous graft of PC-9 were then intravenously injected with anti-PC-9-specific CTLs. Under these conditions, the in-vivo effect of recombinant human (rh) IL-2 and rh IL-12 was evaluated, based on tumor growth. Results. Mice that received either rh IL-2 or rh IL-12 exhibited no inhibitory effect on tumor growth. However, mice that received adoptive immunotherapy (AIT) alone exhibited a significant inhibition of tumor growth in the PC-9 graft in comparison to untreated mice. When mice were treated with AIT combined with rh IL-2 + rh IL-12 administration, tumor growth was significantly suppressed. A significant difference was observed in the growth of the PC-9 graft between AIT + IL-2 + IL-12 treatment and AIT + IL-2 treatment. Four of eight mice in the AIT + IL-2 + IL-12-treated group showed complete tumor regression. Conclusion. IL-12 showed a synergistic effect with adoptive immunotherapy, using CTL in a tumor-engrafted SCID model. These results are therefore considered to provide a sufficient rationale for IL-2 + IL-12-based immunotherapy using CTL transfer for patients with lung cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00012047
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  • 4
    Electronic Resource
    Electronic Resource
    Extended blood half-life of monomethoxypolyethylene glycol-conjugated hen lysozyme is a key parameter controlling immunological tolerogenicity (1999)
    Springer
    Cellular and molecular life sciences 55 (1999), S. 1187-1194 
    Details
    ISSN: 1420-9071
    Keywords: Key words. Immunological tolerance; monomethoxypolyethylene glycol; extended blood half-life; hen egg lysozyme; immunochemistry.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The blood half-life of a protein is prolonged by conjugating a protein with a linear amphiphilic polymer, monomethoxypolyethylene glycol (mPEG). The conjugation gives a protein immunotolerogenicity; hence, it is likely that the long half-life is crucial for the tolerogenicity. We prepared a tolerogenic mPEG conjugate of hen egg lysozyme (mPEG1.5-HEL), which is conjugated 1.5-fold the molecular weight of mPEG against that of HEL, and evaluated the relationship between in vivo stability and the tolerogenicity. mPEG1.5-HEL retained immunogenicity to prime HEL-specific T cell and antibody responses and had a long blood half-life, more than 27 times that of native HEL. The tolerant state was maintained as long as mPEG1.5-HEL was detected in sera. With a decrease in the blood mPEG1.5-HEL level, the tolerant state returned gradually to the responsive state; however, reinjection of mPEG1.5-HEL again restored the tolerance. Thus, the extended blood half-life of HEL by mPEG conjugation is probably vital for establishing and maintaining the tolerant states.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000180050365
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