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Biomedical subjects

E Borek

Publications and source records attributed to E Borek.

At least 19 recordsLinked to original sources
PubMed1988

[Epidemiological research on primary hyperparathyroidism. A prospective multicenter study].

Serum calcium determination of 11,588 hospitalized patients during a twelve-month period revealed hypercalcaemia in 74 (0.64%). Further clinical and biochemical investigation established primary hyperparathyroidism in 20 of them (27%), and in 15 (20%) a malignant tumour (with bone metastases in six) as the cause of the hypercalcaemia. Rarer causes were found in 11 patients (15%): diuretic medication (5), lithium treatment (3), immobilization (2) or hyperthyroidism (1). In the remaining 28 patients (38%) no cause of the hypercalcaemia could be established with certainty. In at least six patients, however, there were clinical pointers towards hyperparathyroidism in the absence of unequivocal biochemical findings. Leaving out of account borderline cases, one must reckon on a prevalence of hyperparathyroidism in 0.17% of an unselected group of hospitalized patients. Parathyroid hyperfunction must always be considered in the differential diagnosis because of its manifold clinical presentation.

Austria↗
PubMed1987

Modified nucleosides in patients with acquired immune deficiency syndrome (AIDS) and individuals at high risk of AIDS: correlations with lymphadenomegaly and immunological parameters.

Patients with certain malignant diseases excrete in their urine elevated levels of modified nucleosides originating predominantly from the breakdown of transfer RNA (tRNA). Acquired immune deficiency syndrome (AIDS), often associated with rapidly progressing Kaposi's sarcoma (KS), is currently occurring in many countries. Male homosexuals are considered to be at highest risk of developing these disorders. We have previously reported that patients with AIDS excrete elevated levels of modified nucleosides. In this communication, we report on modified nucleoside levels measured in 77 male homosexuals without clinical manifestations of AIDS at the time of examination. A high frequency of abnormal nucleoside levels was found in this high-risk group. There was a trend towards higher levels in individuals with lymphadenomegaly, considered a prodrome of AIDS. Statistically significant correlations were found between some of the nucleosides (pseudouridine and dimethylguanosine) and degree of lymphadenomegaly. Pseudouridine, 1-methyl-adenosine and dimethylguanosine were inversely related to percentages of total T-lymphocytes (T11), suppressor T-lymphocytes (T8), and number of natural killer cells (Leu-7). These findings suggest that determination of urinary nucleoside levels may help identify individuals at high risk of developing AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Altered excretion of modified nucleosides and beta-aminoisobutyric acid in subjects with acquired immunodeficiency syndrome or at risk for acquired immunodeficiency syndrome.

Urinary excretion of modified nucleosides and beta-aminoisobutyric acid, subsequently referred to as markers, was determined in populations of patients with acquired immunodeficiency syndrome (AIDS) or at risk for development of AIDS. Our results show that asymptomatic adult male homosexuals excreted elevated amounts of markers as compared to male heterosexuals. This aberrant excretion was more pronounced in asymptomatic adult male homosexuals with antibodies to HTLV-III. Significantly greater excretion of 1-methylinosine, N4-acetylcytidine, and N2-methylguanosine was observed in asymptomatic adult male homosexuals with antibodies to HTLV-III than in asymptomatic male homosexuals without antibodies to HTLV-III. Increased amounts of markers were also excreted by subjects with the generalized or chronic lymphadenopathy syndrome, AIDS related complex (ARC), or AIDS. In these subjects, the most pronounced differences between groups were between subjects with chronic lymphadenopathy syndrome and those with ARC; subjects with ARC excreted greater amounts of seven of the ten urinary markers. There were few differences between subjects with ARC and those with AIDS, Kaposi's sarcoma, or AIDS with opportunistic infections. This observation may be useful for identifying subjects who are at risk of developing AIDS. A prospective study to test this hypothesis is under way.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Modified nucleosides in asbestos workers at high risk of malignant disease: results of a preliminary study applying discriminant analysis.

Patients with asbestos related malignant mesothelioma excrete high levels of modified nucleosides in their urine. The purpose of the present report was to explore further the usefulness of measuring these breakdown products of transfer RNA (tRNA) in male asbestos insulation workers who are at high neoplastic risk but without clinical signs of malignancy. Modified nucleoside levels (psi, m'A, m'I, m2G, and ac4C) were used as discriminator variables in a computer generated discriminant function in which 96% of the controls and 95% of the insulation workers were correctly classified. It was also found, using a similar multiple regression model, that 10 of 13 were correctly classified as having normal chest radiographs and 27 of 30 asbestos exposed subjects as exhibiting alterations in either the parenchyma, pleura, or both. The results suggest that measuring modified nucleosides levels in the urine of asbestos exposed workers, and perhaps others exposed to carcinogenic agents, has the potential for identifying, through multivariate statistical techniques, individuals who are at high neoplastic risk.

Adult↗
PubMed1979

Under-modified Y base in a tRHAPhe isoacceptor observed in tumor cells.

A fluorescent wye (Ye) was isolated from tRHAPhe specific to Ehrlich ascites cells. The structure was determined to be alpha-amino-beta-hydroxy-4,9,-dihydro-4,6-dimethyl-9-oxo-1-H-imidazo(1,2-alpha)purine-7-butyric acid: namely the compound lacking methyl carboxyl and methyl groups and thus is an under-modified precursor of hydroxy-Y base present in normal liver tRNAPhe.

Animals↗
PubMed1979

Quantitative gas-liquid chromatography of neutral sugars in human serum glycoproteins. Fucose, mannose, and galactose as predictors in ovarian and small cell lung carcinoma.

A precise and accurate gas-liquid chromatographic (GLC) method has been developed for the quantitative analysis of the neutral sugars L-fucose (6-deoxygalactose), mannose, galactose, and glucose in ethanol precipitates of human serum proteins. The chromatographic conditions and sample preparation resulted in short analysis time (20 min per run) and made routine analyses practicable (twelve samples per day). The alditol acetate derivatization yielded single derivatives for each sugar. Complete separation was achieved on a 2.0 m X 2 mm I.D. column with 2.0% Silar-7CP on Chromosorb W AW 80--100 mesh. The results of hydrolysis showed that the release of fucose and galactose preceded the release of mannose. Hydrolysis with AG 50 W-X8 (H+) ion-exchange resin in 0.5 N HCl at 100 degrees for 7 h optimized glycosidic bond cleavage with only minimal destruction of fucose, mannose and galactose. A combination of strong cation- and anion-exchange resin columns was used to remove chromatographic background of peptides, amino acids, amino sugars, and inorganic ions. An average R.S.D. of less than 4% with recovery of greater than 86% for the three sugars was achieved. The homogeneity of the chromatographic peaks for the neutral sugars of normal human serum glycoproteins was confirmed by GLC--mass spectrometry. Significantly elevated ratios of fucose, galactose, and mannose to serum protein were observed for patients with small cell lung and ovarian carcinomas.

Carcinoma↗
PubMed1979

tRNA breakdown products as markers for cancer.

Seven breakdown products of tRNA were quantitated by high pressure liquid chromatography in urine and were related to the creatinine content. In the urine of 26 of 27 patients with 13 different malignancies, there was an elevation of one or more of these "markers." The levels of excretion vary approximately with the stage of the disease.

Aminoisobutyric Acids↗
PubMed1979

Patterns of urinary excretion of modified nucleosides.

A recently developed high-performance liquid chromatography method permits quantitative measurement of low levels of modified nucleosides in urine. We report on the patterns of excretion of seven modified nucleosides by normal subjects and cancer patients. It was found that the excretion of these nucleosides expressed as a function of creatinine concentration was constant, not episodic nor related to diet. Thus, randomly collected samples of urine are satisfactory sources for measurement of nucleosides, and the level of nucleosides is of significance when related to creatinine excretion. The constancy of the excretion of the modified nucleosides in normal subjects is quite remarkable. It implies strict metabolic control of transfer RNA turnover. The values for the individual nucleoside/creatinine ratios were found to be significantly elevated in the urine of colon cancer patients.

Adult↗
PubMed1978

Quantitative high-performance liquid chromatography of nucleosides in biological materials.

A rigorous, comprehensive, and reliable reversed-phase high-performance liquid chromatographic (HPLC) method has been developed for the analysis of ribonucleosides in urine (psi, m1A, m1I, m2G, A, m2(2)G). An initial isolation of ribonucleosides with an affinity gel containing an immobilized phenylboronic acid was used to improve selectivity and sensitivity. Response for all nucleosides was linear from 0.1 to 50 nmoles injected and good quantitation was obtained for 25 microliter or less of sample placed on the HPLC column. Excellent precision of analysis for urinary nucleosides was achieved on matrix dependent and independent samples, and the high resolution of the reversed-phase column allowed the complete separation of 9 nucleosides from other unidentified UV absorbing components at the 1-ng level. Supporting experimental data are presented on precision, recovery, chromatographic methods, minimum detection limit, retention time, relative molar response, sample clean-up, stability of nucleosides, boronate gel capacity, and application to analysis of urine from patients with leukemia and breast cancer. This method is now being used routinely for the determination of the concentration and ratios of nucleosides in urine from patients with different types of cancer and in chemotherapy response studies.

Boron Compounds↗
PubMed1978

Tumour-specific phenylalanine tRNA contains two supernumerary methylated bases.

Every malignant tumour examined contains aberrant tRNA methyltransferases and a few tRNAs which are absent from the normal tissue of origin. To determine whether tumour-specific tRNAs have different modifications from those in normal tissue, we purified the most frequently occurring tumour-specific isoaccepting tRNA from two malignant tissues. The isoaccepting phenylalanine tRNA from Novikoff hepatoma and Ehrlich ascites cells both contain two supernumerary methylated bases. One of these l-methylguanine, is absent from the phenylalanine tRNA of normal rat, mouse, rabbit and calf liver. An increase in the levels of 5-methylcytidine and dihydrouridine was also detected.

Animals↗
PubMed1978

Lysine transfer RNA2 is the major target for L-ethionine in the rat.

Ethionine, a hepatocarcinogen, ethylates macromolecules in vivo especially tRNA of rat liver. When rats were injected with L-[ethyl-3H]ethionine, the tRNA fraction of the liver was found to be labeled. One tRNA with the highest specific activity was purified and identified as lysine-tRNA2.

Animals↗
PubMed1978

Dual-column cation-exchange chromatographic method for beta-aminoisobutyric acid and beta-alanine in biological samples.

A rapid, automated chromatographic method has been developed for the quantitation of the nucleic acid catabolites beta-aminoisobutyric acid and beta-alanine in urine, serum, and other physiological fluids. The analyses were performed on a modified Beckman 121M amino acid analyzer with dual ion-exchange columns and the use of a single sodium citrate buffer (pH 4.38, 0.20 mol/liter). By carefully matching the elution pattern for the two ion-exchange columns and alternating use of these columns, analyses are completed every 40 min. The chromatography, regeneration, and equilibration of the two columns are precisely programmed, thus the detector sees only the elution of beta-aminoisobutyric acid and beta-alanine alternately from each column. Long-term precision and analytical recovery for the two metabolites in urine were 1.9 and 102%, and 3.3 and 101%, respectively. Their normal physiological values were determined in human serum and urine. Their excretion in the urine was also studied as a function of collection time, to validate a more convenient, less costly method of sampling. This study shows that randomly collected samples are acceptable when the concentration of the two metabolites are expressed in terms of creatinine excretion. In addition, the distribution of the free and conjugated forms of the two metabolites in urine and serum was studied. A preparative method was also developed for the quantitative isolation of beta-amino-isobutyric acid from urine samples. The alternating dual-column technique may be applied to any ion-exchange chromatographic method where many analyses must be performed. This method is currently used in our laboratories for measuring these beta-amino acids in urine and serum of patients with various types of cancers.

Alanine↗
PubMed1977

Composition, associated tissue methyltransferase activity, and catabolic end products of transfer RNA from carcinogen-induced hepatoma and normal monkey livers.

This investigation was designed to explore transfer RNA (TRNA) methyltransferase activity, urinary excretion levels of tRNA degradation products, and tRNA base composition in normal monkeys and in those with hepatocellular carcinomas induced by N-nitrosodiethylamine. After the development of the tumor, 24-hr urine specimens were collected, the monkeys were sacrificed, and the livers were removed for tRNA isolation and methyltransferase activity studies. The tRNA methyltransferase activity and capacity and the urinary excretion levels for selected tRNA degradation products (pseudouridine, N2,N2-dimethylguanosine, 1-methylinosine, 7-methylguanine, and beta-aminoisobutyric acid) were elevated for the hepatoma-bearing monkeys when compared to those with normal liver. The isolated tRNA pools were analyzed by high-resolution liquid chromatography, and similar base compositions were found for the hepatoma-bearing and normal monkeys. With the use of methyl-deficient Escherichia coli tRNA as the methyl receptor and the analytical procedure for tRNA anlysis, the methylating ability of the tRNA methyltransferases in hepatoma and normal liver extracts was determined. The hepatoma methyltransferase homogenates were found to produce increased levels of 7-methylguanine, N2,N2-dimethylguanine, and thymine, while the normal liver extracts gave higher levels of N2-methylguanine. These differences were not apparent in the base composition of the tRNA pools. The increased urinary excretion and higher methyltransferase activity of the hepatoma-bearing monkeys without an apparent increase in the methylated base content of their tRNA suggest increased tRNA tf individual isoaccepting tRNA's would be missed by analyzing the tRNA pools. The variations in the individual tRNA methyltransferase activities of the hepatoma and normal liver homogenates indicate a difference in the methlation of their tRNA's.

Animals↗