Large amounts of neopterin are produced and released from human macrophages on stimulation with interferon-γ. Neopterin is biologically stable, and it can be easily quantified in human body fluids. Neopterin measurements are useful to monitor allograft recipients to detect immunological complications. In autoimmune diseases, neopterm concentrations reflect the extent and activity of the disease. In infectious syndromes and in patients with cancer, neopterin concentrations provide prognostic information. In addition to providing clinically useful information, neopterin monitoring allows insight into the immunopathogenesis of a variety of diseases.
Since October 1986, all volunteer blood donors in the Tirol of Austria have been tested for neopterin. Serum neopterin levels were raised in 1242 donors (1.6%), 650 of whom (52.3%) consented to another test four weeks after the donation. In retrospect, 148 of these donors (22.8%) had an illness or abnormal symptoms at the time of donation or within a few days of it: according to the "guidelines for blood group testing and blood transfusion" of the Federal German Chamber of Doctors (Deutsche Bundesärztekammer) 25 of these (16.9%) should be permanently excluded as blood donors. The other 123 donors would have been temporarily excluded, according to the guidelines, if their illness had been known at the time of donation. Since the beginning of 1988, all donated blood with increased serum neopterin levels also had an IgM test for cytomegalovirus (CMV): nine of 243 samples tested (3.7%) indicated an acute CMV infection. The neopterin assay thus detects a variety of potentially harmful diseases or conditions which would not be revealed by the usually employed battery of routine tests.
A purification process for the monclonal anti-CD4 antibody MAX.16H5 was developed on an analytical scale using (NH&SO, precipitation, anion-exchange chromatography on MonoQ or Q-Sepharose, hydrophobic interaction chromatography on phenylSepharose and gel filtration chromatography on Superdex 200. The purification schedule was scaled up and gram amounts of MAX.16H5 were produced on corresponding BioPilot columns. Studies of the identity, purity and possible contamination by a broad range of methods showed that the product was highly purified and free from contaminants such as mouse DNA, viruses, pyrogens and irritants. Overall, the analytical data confirm that the monoclonal antibody MAX.16H5 prepared by this protocol is suitable for human therapy.
Summary: Biological processes which inight explain the association of pteridine excretion with proliferation are still unknown. Difficulties in the analysis and the determination of naturally occurring pteridines are described. The best quantitative estimations were achieved when measurement of non-reduced forms was attempted. The performance characteristics of such a method for neppterin by high performance liquid chromatography on reversed phase are given. Enhanced proliferation and dedifferentiation in cell cultures and organisms is paralleled by excretion of unconjugated pteridines into the medium or urine. Urinary neopterin in healthy subjects and in patients with benign diseases was only significantly raised in patients with viral diseases. Howevei, an elevation of urmary neopterin occurred in a wide variety of malignant diseases. In haematologic neoplasias correlatipns of neopterin values to clinicäl features, to tumour staging, and to laboratory data were apparent. The clinicäl Utility of neopterin measurement was also demonstrated in patients with gynaecologic tumours, particularly in patients with ovarian carcinoma. In both homogenepus patient groups the neopterin assay may provide an additional aid for prognosis and for monitoring therapy. Comparison of the neopterin assay with already established tumour marker substances at least revealed no inferiority in sensitivity. The present results justify extensive investigations in prder to eväluate further the clinicäl applicäbility of the neopterin assay.
Pteridine in der Diagnostik von Neoplasien
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