Urinary pseudouridine excretion in myelomatosis

Abstract

Sunmary Urinary ql excretion is independent of the main indices of tumour activity in myelomatosis (serum paraprotein, serum ,B2-microglobulin, serum creatinine and urinary light chain production). The mean (±s.d.) at presentation was 40.7 + 22.6 nmol . ,umol ucr 1, compared to 25.4 + 4.8 nmol . gmol ucr-in controls. Urinary levels at presentation are significantly related to prognosis, the higher the level the poorer the prognosis. However, when these levels have been stratified according to the corresponding level of serum /B2 m, the level adds little as a prognostic factor.Several biochemical indices have been found to be valuable as guides to prognosis in myelomatosis, they include serum creatinine, paraprotein urinary free light chain excretion and haemoglobin levels (Durie & Salmon, 1975). More recently the serum f2-microglobulin level has been confirmed to be a powerful prognostic indicator (Child et al., 1983;Bataille et al., 1984, Cuzick et al., 1985. Nevertheless, the variation of the course of the disease within the subsets defined by combinations of these indicators warrants further study to try to improve our predictions at the individual patient level.There is growing evidence that the increased urinary excretion of modified nucleosides is a common feature of many types of advanced cancers including lymphomas (Salvatore et al., 1983;Rasmunson et al., 1983). The modified nucleosides are produced by post-transcriptional enzymatic action; tRNA contains the highest and most varied number of modified nucleosides. No retrieval pathway exists for these compounds, ensuring that they are not randomly inserted into the macromolecules (Borek, 1983;Dirheimer, 1983). The catabolites of tRNA are excreted into the urine without reabsorption and consist of pseudouridine (i/) and possibly as many as 50 methylated nucleosides. Pseudouridine is generally excreted in concentrations of 10 to 100 times that of other modified nucleosides both in healthy subjects and cancer patients. There are previous reports indicating that l excretion levels tends to carry as much information in terms of its relation to tumour mass and activity as a formal analysis of the spectrum of modified nucleosides (Rasmunson et al., 1983); but others favour the simultaneous analysis of several nucleosides Heldman et al., 1983).In this paper we report the levels of urninary / excretion in myelomatosis, determine its role as a prognostic indicator alone, and investigate whether it can add information once the patients have been stratified for serum f2m levels. Materials and methods PatientsThe 264 patients were all entered into the Medical The urinary nucleosides were first isolated by affinity chromatography on boronate Affi-gel 667 obtained from Bioard (Watford, UK), as described by Gehrke et al. (1978). Pseudouridine was then assayed by reverse phase chromatography on a 300 x 5 mm Spherisorb 5 ODS column in conjunction with an Applied Chromatography Systems HPLC apparatus, and the absorbance monitored at 254 nm, 0.1 AUFS, 20 M1 of reconst...

Blood Plasma Pseudouridine in Patients with Malignant Proliferative Diseases

“…3). This is in agreement with the findings of Sorensen et al (6), who demonstrated that urinary pseudouridine excretion in multiple myeloma usually exceeds that in other neoplasms, and there is a highly significant linear trend towards a negative prognosis with a rising concentration of urinary pseudouridine. It is interesting that in mice carrying a transplantable myeloma tumour no increase in the serum pseudouridine concentration was seen, despite the presence of a considerable tumour burden (30).…”

“…The measurement of urinary excretion of pseudouridine, 7-methylguanine, and N 2 ,N 2 -dimethyl-guanosine was used to assess whole-body turnover of rRNA, mRNA, and tRNA in preterm infants and adults (3,4). Pseudouridine is generally excreted in concentrations of 10 to 100 times that of other nucleosides, both in healthy subjects and cancer patients (5,6). The source of pseudouridine detected in urine is whole-body catabolism of tRNA and rRNA (3,4).…”

Efficiency of Hemodialysis of Pyrimidine Compounds in Patients with Chronic Renal Failure

“…Therefore, urinary excretion of pseudouridine and its concentration in blood plasma, with efficient kidneys, is a good index of the whole-body tRNA + rRNA turnover. Numerous attempts of applica tion of pseudouridine level in blood plasma and urine as a tumor marker are reported [3][4][5][6][7].…”