[Neopterin today].
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Biomedical subjects
H Rokos
Publications and source records attributed to H Rokos.
Rat liver iodothyronine monodeiodinase. Evaluation of the iodothyronine ligand-binding site.
Ligand binding characteristics of rat liver microsomal type I iodothyronine deiodinase were evaluated by measuring dose-response inhibition and apparent Michaelis-Menten or inhibitor constants of iodothyronine analogues to compete as substrates or inhibitors for the natural substrate L-thyroxine. These data show strong correlations with the binding requirements of hormone analogues to serum thyroxine-binding prealbumin since iodothyronine analogues with a negatively charged side chain, a negative charge or hydrogen bonding function in the 4'-position, tetraiodo ring substitution, and a skewed hormone conformation are structural features shared in common which markedly affect enzyme activity and protein binding affinity. 3,3',5'-Triiodo-L-thyronine is the most potent natural substrate (IC50 = 0.3 microM) and tetraiodothyroacetic acid is the most potent inhibitor (IC50 = 0.2 microM). Both thyroxine (T4)-5'- and T4-5-deiodination pathways are inhibited by these potent analogues, providing further evidence for a single enzyme catalyzing the rat liver microsomal deiodination reactions. These data also show that L-hormone analogues are preferentially deiodinated via the T4-5'-deiodination pathway, whereas D-analogues produce products via the T4-5-deiodination pathway. The thyroxine-binding prealbumin complex was used to model the interaction of thyroid hormones with the deiodinase active site. Computer graphic modeling of the prealbumin complex showed that only those analogues which are potent deiodinase inhibitors or substrates can be accommodated in the hormone binding site. This model suggests the design of functionally specific ligands which can modulate peripheral thyroid hormone metabolism and act as antithyroidal drugs.
Animals↗
[Results of a phase II study on the treatment of hairy cell leukemias with various doses of alpha-2-recombinant interferon].
Hairy-cell leukemia has been shown to be extraordinary sensitive to treatment with alpha-interferon. In order to define clinically effective interferon doses associated with minimal toxicity two different dose regimens were applied in this clinical trial: firstly, a conventional dose schedule, and secondly, a biologically defined dose regimen. For dose finding in the latter group, neopterin, a GTP degradation product produced by macrophages under control of interferon, was chosen. Six patients (Group A) received conventional doses of recombinant interferon--alpha-2 (rIFN-alpha-2) 3 X 10(6) U/sqm/daily by the subcutaneous route. Five patients (Group B) were treated with the minimal dose of rIFN-alpha-2 which had previously been shown to induce maximum neopterin levels in urine. Already interferon doses in the range of 3 to 5 X 10(5) U/sqm2/daily administered subcutaneously proved to be sufficient for triggering maximum neopterin excretion in the urine. After six months of interferon treatment all patients were evaluable. At this time both doses regimens proved to be effective in terms of their anti-leukemic activity, but differed significantly in toxicity, which was only seen in Group A patients.
Adult↗
Molecular structure and biochemical activity of 3,5,3'-triiodothyronamine.
The thyroid hormone decarboxylation product, 3,5,3'-triiodothyronamine (T3AM), has been shown to inhibit the cAMP production stimulated by isoproterenol in turkey erythrocytes. This adrenergic receptor binding inhibition was not shown by the thyroid hormones nor by tyramine, but was observed for 3,5-diiodotyramine, 3,5-diiodothyronamine, and thyronamine. T3AM also inhibits prolactin secretion in cultured pituitary cells as well as domperidon binding in rat corpora striata membranes. T3AM has no thyromimetic activity at the nuclear level. The molecular structure of T3AM, determined as a borosalicylate salt by X-ray diffraction techniques, is the first report of a decarboxylated thyroid hormone analogue.
Animals↗
Raised serum neopterin levels and imbalances of T-lymphocyte subsets in viral diseases, acquired immune deficiency and related lymphadenopathy syndromes.
D-erythro-neopterin, a biochemical marker of cell-mediated immune response, was found to be significantly (p less than 0.001) elevated in the serum of homosexual patients with acquired immunodeficiency syndrome and related lymphadenopathy syndrome. The most pronounced rise was observed in viral diseases causing a numerically measurable activation of the immune system such as EBV or CMV infections. In the latter patient groups, the increase in T8+, HLA-DR+ and monocytic antigen+ lymphocyte subsets correlated with the raised neopterin level. Thus, neopterin seems to be released under various conditions in viral diseases and may reflect a functional state of T-lymphocytes irrespective of the actual number expressing differentiation antigens on the cell surface.
Acquired Immunodeficiency Syndrome↗
[A radiochemically stable, T4-analogous tracer of high specific activity suitable for the measurement of FT4].
Explore the source record for details and available documents.
Humans↗
[Synthesis and investigation of substituted iodothyronines with the aim of obtaining radiochemically stable 125I-tracers of high specific activity (author's transl)].
Various substituents were tested for their ability to replace 3'-iodine of T4 without affecting binding to T4 antibodies and without exchanging with 125I during synthesis of high specific activity T4. Measured cross-reactivities of 3'-bromo-T3 and 3'-isopropyl-T3 relative to T4 were 85.6 and 8.9%, respectively, thus suggesting a high contribution of the ionised 4'-hydroxy group to antibody binding. The 3'-bromo substituent is not exchanged with 125I during labelling by the chloramine-T method. Therefore, 3'-bromothyronines are suitable starting materials for the synthesis of 3'-bromo-5'-125iodothyronines of high specific activity; these have the advantage of a long shelf life comparable to [125I]T3, because only 125I-monolabelled thyronines are produced.
Chemical Phenomena↗
Altered urinary excretion of pteridines in neoplastic disease. Determination of biopterin, neopterin, xanthopterin, and pterin.
Urinary pteridine concentrations in healthy control subjects and patients with cancer and non-malignant diseases were determined by HPLC and TLC after partial purification by ion exchange and Sephadex chromatography. Elevated concentrations of neopterin were found in 70% of the 50 cancer patients investigated. In patients with non-Hodgkin's lymphoma (seven cases) or with liver metastases (12 cases) neopterin concentrations were significantly higher than in control subjects (p < 0.01). Biopterin was less frequently increased (22%). Xanthopterin was generally raised when neopterin and/or biopterin excretion was high. Neopterin/biopterin ratios were higher in some patients with cancer or with severe renal insufficiency than in controls. These findings suggest that alterations in pteridine metabolism are common in malignant disease. The pathogenic, diagnostic and therapeutic significance of these changes remains to be established.
Biopterins↗
Biosynthesis of riboflavin. 6,7-Dimethyl-8-ribityllumazine 5'-phosphate is not a substrate for riboflavin synthase.
Phosphotransferase from carrot is shown to catalyze the phosphorylation of 6,7-dimethyl-8-ribityllumazine specifically at position 5' of the ribityl side chain. The lumazine 5'-phosphate is neither a substrate nor an inhibitor of riboflavin synthase from Bacillus subtilis and Escherichia coli. It follows that the obligatory product of riboflavin synthase is riboflavin and not FMN.
Bacillus subtilis↗
[Purines. IX. A new mild purine synthesis].
Explore the source record for details and available documents.
Chemical Phenomena↗
Serial transplants of DMBA-induced mammary tumors in Fischer rats as model system for human breast cancer. IV. Parallel changes of biopterin and melatonin indicate interactions between the pineal gland and cellular immunity in malignancy.
Nocturnal (23.00-07.00 h) urinary melatonin and total biopterin (tBI; after acidic oxidation of reduced biopterins) were analyzed during the growth of two passages of a mammary tumor line in female F344 Fischer rats. In addition, nocturnal (02.00-03.00 h) peak concentrations of pineal melatonin in plasma were analyzed when tumors had reached comparable average tumor volumes of 25-30 cm3. Since tetrahydrobiopterin (BH4) is produced by murine macrophages in response to interferon-gamma released by activated T lymphocytes, measurements of tBI can serve to estimate the state of cellular immunity. At passage 2, a slow-growing localized carcinosarcoma, tBI showed a progressing increase during tumor growth reaching more than 200% (p < 0.05-0.005) of controls by the end of the experiment. Urinary and plasma melatonin were elevated by 30-50% (p < 0.05) and 42% respectively. At passage 12, a fast-growing metastasizing sarcoma, a depression of about 20-30% was found for tBI (p < 0.05) and urinary melatonin (p < 0.025); plasma melatonin was depleted by 70% (p < 0.005). Parallel changes of both parameters at each tumor passage indicate a close link between the pineal hormone melatonin and cellular immunity. The opposite trends observed at the two passages indicate a clear stimulation of the immune system and the pineal gland at early but inhibition at advanced stages of cancer.
9,10-Dimethyl-1,2-benzanthracene↗