Search PubMed⌕ Search

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↗
PubMed1984

Transfer RNA breakdown products in the urine of asbestos workers.

Patients with malignant mesothelioma, a neoplasia strongly associated with previous asbestos exposure, excrete in the urine high levels of modified purines, pyrimidines, and their ribosides, breakdown products of transfer RNA. The urinary excretion levels of modified nucleosides were measured in 47 male insulation workers with long term exposure to asbestos and, therefore, at high neoplastic risk. The nucleoside levels of 44 male control subjects were used for comparison. Asbestos-related radiographic changes were found in 70% of the exposed individuals. An increasing severity of radiographic alterations was associated with a greater frequency of elevated nucleoside clusters, especially in m'A, m'I, m'G, and m2(2)G. Duration since onset of exposure was directly related to pseudouridine, m'I, and m2(2)G. Though cigarette smoking contributes to the development of asbestos-related lung cancer, data are presented that support the hypothesis that asbestos exposure is the more important factor related to the elevated values of nucleosides. It was concluded, therefore, that measuring nucleoside levels in populations at high risk of developing certain kinds of cancer may provide a useful diagnostic tool for detecting "preclinical" biochemical changes that may be predictive of future neoplastic manifestations.

Adult↗
PubMed1983

Urinary nucleic acid breakdown products as markers for trophoblastic diseases.

A feasibility study on the use of urinary nucleoside markers for the management of trophoblastic disease is presented. The markers return to normal rapidly after effective therapy, whereas the human chorionic gonadotropin levels remain elevated longer before reaching normal. If this finding is valid in a larger number of patients, it may spare patients with trophoblastic disease needless continuation of chemotherapy.

Body Weight↗
PubMed1983

New applications of urinary nucleoside markers.

In order to extend the usefulness of the quantitation of urinary nucleoside markers, studies were undertaken to explore the adaptability of such determinations for early detection in cancer-prone populations such as asbestos workers. Another study was aimed at exploring the usefulness of therapy in individual patients. During these studies, two heretofore unknown phenomena serendipitously emerged which expand the versatility of the marker determinations: (a) radiation damage in animals and humans causes an excretion of urinary BAIB which from preliminary studies appears to be proportional to the irradiation burden, and (b) lead poisoning in the human also produces BAIB excretion. Some of the practical uses of these determinations are self-evident. Among 13 asbestos workers without clinical symptoms, eight were found to have significant elevations of the marker levels. Nine asbestos workers with diagnosed mesothelioma all excreted two or more markers at high levels. Some of the psi levels were the highest seen. Currently the diagnosis of mesothelioma is difficult and painful, requiring a rib resection; however, an asbestos worker with such elevations--provided small cell carcinoma of the lung is ruled out--can be seriously suspected of having mesothelioma. In a study of the usefulness of the markers in following therapy of trophoblastic disease, these markers were determined in women with incipient invasive hydatidiform mole. After curettage, the nucleoside markers indicated absence of residual disease but the usual marker, HCG, was still markedly elevated. The women were followed up for 2 years and were found to remain symptom-free. Therefore the source of the nucleoside markers is cleared more rapidly than that of HCG.

Adult↗
PubMed1983

Urinary excretion of modified nucleosides in patients with malignant mesothelioma.

Transfer RNA is the most complex biomacromolecule in both structure and function. The complexity of its structure is caused by a large variety of enzymes which add modifying groups to the four bases after the primary synthesis. The most abundant of these enzymes are the transfer RNA methylases, which add methyl groups at various positions in the macromolecule. These methylating enzymes were found to be, without exception, aberrantly hyperactive in every malignant tumor examined. In turn, every malignant tumor contains a few transfer RNAs that are different in structure from the transfer RNAs in the normal tissue. Again, there is no exception. These are the first qualitatively different biochemical components of every malignant cell, not more or less but different transfer RNAs. The late Alexander Gutman observed that cancer patients excrete in their urine elevated levels of certain methylated bases. From the structure of these bases and our knowledge of their method of synthesis, it became apparent that most of them come from the breakdown of transfer RNA. Their elevation in the urine stems from an extraordinarily high rate of turnover of transfer RNAs in tumor tissue. Highly sophisticated, sensitive methods of analysis were developed for the determination of the modified nucleosides in the urine of cancer patients. When related to the creatinine level of the urine, some of the modified nucleosides and products derived from them were elevated in a large variety of tumors. Perhaps more importantly, it was found that these elevated levels return to normal after effective chemotherapy. Thus, these markers may also be useful in monitoring the effectiveness of therapy. We report here initial studies on the detection of cancer in asbestos workers and possible premalignant conditions in workers with asbestosis.

Adult↗
PubMed1983

Tumor markers derived from nucleic acid components.

It was known for some time that cancer patients excrete in their urine elevated levels of modified nucleosides. From earlier work, we were able to show that most of these modified nucleosides originate from transfer RNA (tRNA). The modifications are achieved at the macromolecular level by enzymes after primary synthesis. Such modifications are highly specific and, therefore, when the modified nucleosides accumulate from the tRNA breakdown, they cannot be reinserted randomly by the polymerases and must be excreted. We found that the modifying enzymes are aberrantly hyperactive in every malignant tissue. We also found that there is abnormally high turnover of tRNA in malignant tissues, which is probably the source of the elevated levels of excretion products. Since these products originate from a cardinal component of the molecular biology of every cell, the determination of markers in the urine may be a universal indicator of malignancy. We are focusing on the use of these markers in syndromes whose diagnoses are otherwise difficult. Since the marker levels return to normal very soon after chemotherapy, such determinations can be used to monitor the effectiveness of therapy. Therefore, the clinical oncologists can adapt their protocols to the specific need of a patient.

Chorionic Gonadotropin↗
PubMed1982

Biological markers and small cell carcinoma of the lung: a clinical evaluation of urinary ribonucleosides.

Five minor base ribonucleosides, primarily degradation products of transfer ribonucleic acid (tRNA), were evaluated as potential biological markers for patients with small cell carcinoma of the lung. The urinary concentration for pseudouridine, 1-methyladenosine, 1-methylinosine, N2-methylguanosine, and N2,N2-dimethylguanosine was determined by means of reversed-phase high performance liquid chromatography and quantitatively expressed as a function of creatinine excretion. Comparisons were made with carcinoembryonic antigen (CEA) plasma levels. The total frequency of elevated values for the five nucleosides in pretreatment urine samples was directly related to stage of disease with 24/60 (40%) determinations increased in 12 patients with limited disease and 69/85 (81%) in 17 patients with extensive disease. For these same patients, CEA levels were elevated respectively in 2/11 (18%) of the former and 9/17 (53%) of the latter group. The frequency and degree of elevation of the nucleoside/creatinine ratios in pretreatment samples from patients with extensive disease was correlated directly with increasing number of metastatic sites. Of the five nucleosides, the mean number elevated was two for limited disease, 3-4 for extensive disease with one metastatic site, 4 for two or three, and 5 for four or more sites of metastases. Based on a summation of pretreatment nucleoside/creatinine ratios, a discriminant for survival was derived giving curves separating patients (P = 0.086) similar to the discriminant based on stage of disease. Although discordant results were noted, an overall correlation of 75% agreement with clinical assessment was estimated in response categories when monitoring changes associated with therapy.

Antineoplastic Agents↗
PubMed1982

Changes of post-transcriptional modification of wye base in tumor-specific tRNAPhe.

Nucleotide sequences of normal mouse liver tRNAPhe and tumor-specific tRNAPhes isolated from Ehrlich ascites tumor and neuroblastoma cells were examined by post-labeling techniques. The results showed that their sequences are identical, except for changes in post-transcriptional modifications that are located in the anticodon region. Normal mouse liver tRNAPhe contained Cm32, Gm34 and YOH37. On the other hand, tumor-specific tRNAPhes were found in one of two possible configurations: 1) Cm32, Gm34 and Y*OH37 (under-modified YOH) or 2) C32, G34 and m1G37. The ratio of the two forms of tRNAPhes differed in different tumor cells; Ehrlich ascites tumor tRNAPhe had mainly Y*OH-containing tRNAPhe whereas neuroblastoma tRNAPhe has predominantly m1G-containing tRNAPhe. It was concluded that tumor-specific tRNAPhes are products of different extents of modification, rather than of new tRNA transcription.

Animals↗
PubMed1982

Modified ribonucleosides as biological markers for patients with small cell carcinoma of the lung.

A variety of individual modified ribonucleosides may be elevated in the urine of cancer patients. They can be readily measured quantitatively in a single reversed-phase high-performance liquid chromatographic run. A total of 41 patients with small cell carcinoma of the lung were studied. For 5-ribonucleosides determined in the pretreatment urine of 28 patients, the respective frequency of elevation was directly related to stage of disease. One or more nucleosides were evaluated in the pretreatment urine of 27 out of 28 patients (96%). Included were 11 patients with limited disease and 10 (91%) had 2 or less than 2 nucleosides elevated, whereas 16 out of 17 (94%) with extensive disease had 3 or more elevated. Based on this same discriminant, median survival was significantly extended for patients with 2 or less nucleosides elevated (24 months) in contrast to 3 or more (10 months). Using a single number to represent the summation of equally weighted individual nucleoside values as a composite score, a direct relationship was found between increasing extent of disease or tumor burden. This was in contrast to more variable results for carcinoembryonic antigen analyzed in plasma samples obtained at the same time. When determined serially the composite score paralleled in general the clinical response categories for individual patients.

Carcinoembryonic Antigen↗
PubMed1982

Inhibition of mRNA methylation: an approach to specific inhibition of viral replication.

Eukaryotic mRNAs and most viral mRNAs contain very extensive modification on the 5' end consisting of the "cap," part of which is a guanine which is methylated in the 7-position. It is quite well established that the methylated cap is essential for the efficient translation of the mRNA. In a search for an effective chemotherapeutic agent, Dr. Roland Robins synthesized the compound ribavirin; this compound turned out to be an extraordinarily effective virostatic agent against both RNA and DNA viruses. Given the capping of the mRNAs produced by both types of virus, and, given the structure of ribavirin, it seemed to us that it may be fruitful to explore whether this drug might act in both cases by blocking the capping reaction. Such a mechanism indeed turned out to be a reality. We have shown that ribavirin triphosphate acts as a competitive inhibitor for the capping of mRNAs. We and others have shown that uncapped mRNAs are poorly translated. An interesting corollary confirmation of these findings is that encephalomyocarditis virus (EMC) and polio virus generate mRNAs which are not capped, and ribavirin is innocuous to these viruses. Another agent which acts as an inhibitor of mRNA methylation emerged from subsequent efforts. It is known from the work of Ian Kerr that extracts of interferon treated cells in the presence of double stranded RNA synthesize a unique 2'-5'-linked oligo (adenylic acid) 5'-triphosphate, a small trinucleotide of unusual structure, which inhibits protein synthesis. We have explored its effect on the methylation of mRNA and found it to be a potent inhibitor of methylation of the cap. Thus, two agents are known which inhibit methylation of mRNA and they may serve as prototypes for designing other such inhibitors, with a view to specific inhibition of mRNAs foreign to the host.

HeLa Cells↗