Antigen improving

Partin AW, Brawer MK, Bartscli G, et al Complexed prostate specific antigen improves specificity for prostate cancer detection Results of a prospective multicenter clinical trial. J Urology 2003 170 ... 

Likewise, modification of either PheB 1 or LysB29 has been shown to improve the pharmaceutical performance (eg., increased plasma half-life, reduced immuno-genicity and antigenicity, improved resistance to proteolysis, increased aqueous/ organic solubilities) of the insulin conjugates thus produced while not significantly... 

The first SRS-A antagonist, FPL-55712 (26) (149), was discovered before the stmctures of the leukotrienes were detemiined. Although this compound is relatively weak as an antagonist and suffers from a very short half-life in vivo, it played an important role both in leukotriene stmcture elucidation and as a model for later antagonists. In work stmcturaHy related to FPL-55712, LY-171883 was developed (27) (150). LY-171883 was evaluated in several clinical trials before development was stopped. Orally adrninistered, LY-171883 blocked slightly the response to aerosol LTD improved pulmonary function (FEV ) in mild asthmatics (151), decreased the sensitivity of asthmatics to cold air-induced bronchoconstriction (152), and significantly reduced the bronchoconstrictor response to inhaled antigen (153). However, in all these studies the beneficial effects were minimal. 

Adjuvants are substances which can modify the immune response of an antigen (139,140). With better understanding of the functions of different arms of the immune system, it is possible to explore the effects of an adjuvant, such that the protective efficacy of a vaccine can be improved. At present, aluminum salt is the only adjuvant approved for use in human vaccines. New adjuvants such as QS-21, 3D-MPL, MF-59, and other liposome preparations are being evaluated. Several of these adjuvants have been in clinical trial, but none have been approved for human use. IL-12 has been proposed as an adjuvant which can specifically promote T-helper 1 ceU response, and can be a very promising adjuvant for future vaccine development. 

Commercial use of cell and tissue culture continues to expand. Improvement of organisms through recombinant nucleic acid techniques has become commonplace. Formerly, a few laboratories were well ahead of most others, but now the methods have been perfected for routine use. Another technique that is widely practiced is culturing of cells that excrete high concentrations of just one antibody protein. The specificity of antibodies and antigens is exploited in medical testing procedures using these pure monoclonal antibodies. 

There are a number of practical problems involved with using polysaccharides as vaccines as there are frequently too many different chemotypes for it to be practicable to prepare a vaccine. In some cases a limited number of serotypes are the dominant cause of infection and it may then be possible to produce vaccines. A major problem is the poor immune response elicited by polysaccharide antigens, which may in some cases be improved by chemical modification. This is (fie case for vaccines for Haemophilus influenzae type b (a causative agent of meningitis), where the antigenicity of the polysaccharide can be increased by coupling to proteins. 

Kure K, Lyman WD, Weidenheim KM, Dickson DW (1990a) Cellular localization of an HlV-1 antigen in subacute AIDS encephalitis using an improved double-labeling immunohistochemi-cal method. Am J Pathol 136(5) 1085-1092... 

Fractionation. The process by which components are extracted firm bacterial eells or from the medium in whieh the baeteria are grown and obtained in a purified form. The polysaccharide antigens of Neisseria meningitidis are separated from the bacterial cells by treatment with hexadecyltrimethylammonium bromide and those of Streptococcus pneumoniae with ethanol. The purity of an extracted material may be improved by resolubilization in a suitable solvent and precipitation. After purification, a component may be dried to a powder, stored indefinitely and, as required, incorporated into a vaccine in precisely weighed amounts at the blending stage. 

The sterols and sterolins in rice bran are potent immunomodulators. The best response was obtained with a 100 1 sterol/sterolin mixture that demonstrated T-cell proliferation from 20% to 920% and active cell antigens after four weeks in human subjects (Bouic et al, 1996). Another in vitro experimental study with sterol/sterolins, demonstrated a significant increase in cytokinines, interleukin-2 and y-interferon between 17% and 41 % in addition to an increase in natural killer cell activity. These experiments (Bouic et al, 1996) prove that sterol/sterolins are potent immunomodulators with important implications for the treatment of immune dysfunction. Rice bran products are excellent dietary supplements for the improvement of immune function. It is probable that the effects of rice bran on diabetes, CVD and cancer all result from improved immune function. 

Complement induced immune lysis of cells and liposomes to release markers which are then detected electrochemically has been used to detect antibodies and antigens in a homogeneous format at nanomolar levels 252-256) qqjJj amperometric and potentio-metric electrodes have been employed. Unfortunately, major improvements in sensitivity appear unlikely, and instability of liposomes makes development of stable reagents for commercial systems difficult. 

Molecules 11 rapidly and irreversibly inhibit the DPP IV activity of the CD26 antigen, with IC50 values in the nanomolar range. Cycle enlargement ( = 4 instead of 2) improves inhibitory activity, whereas increasing the alkyl chain length on the sulfur atom R has no apparent effect. Other aminopeptidases are not inhibited. Molecules 11 inhibit DPP I V-p, an isoform of DPP IV, much more poorly.32,56... 

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