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W Lutz

Publications and source records attributed to W Lutz.

At least 55 records · Page 3Linked to original sources
PubMed1997

In vivo regulation of single copy and amplified N-myc in human neuroblastoma cells.

Amplification with subsequent overexpression of N-myc is a recurrent genomic alteration of neuroblastoma cells. DMS-in-vivo-footprinting of the basal promoter of the human N-myc gene (positions -221 to +21) revealed three changes in promoter architecture that are clustered in a 50 bp region and included (1) protein binding to two overlapping E2F-sites, (2) extreme hypersensitivity of guanine - 159, and (3) a short stretch of single stranded DNA with a single protected guanine. While in transient assays the basal promoter activated gene expression in all cell lines analysed, the changes at the endogenous promoter were restricted to neuroblastoma cells with strong N-myc expression. The hypersensitivity of guanine -159 could result from protein binding to a flanking, evolutionary conserved 5'-CCTCCC-3'-element, referred to as CT-box, that was bound in vitro in a Zn2+-requiring manner by a protein from nuclear extracts of neuroblastoma cells. Four copies of the CT-box in front of an N-myc minimal promoter (-60 to + 18) activated expression of a reporter gene in transient transfections whereas four copies of the mutant element did not. Our data add N-myc to a growing list of mammalian genes with CT-boxes that bind proteins in a Zn2+-dependent manner. Moreover, the data suggest that a common mechanism controls N-myc expression in neuroblastomas irrespective of N-myc copy number, and that in cell lines with amplification all gene copies contribute to N-myc expression.

Animals↗
PubMed1997

Doubling of world population unlikely.

Most national and international agencies producing population projections avoid addressing explicitly the issue of uncertainty. Typically, they provide either a single projection or a set of low, medium and high variants, and only very rarely do they give these projections a probabilistic interpretation. Probabilistic population projections have been developed for specific industrialized countries, mostly the United States, and are based largely on time-series analysis. On a global level, time-series analysis is not applicable because there is a lack of appropriate data, and for conceptual reasons such as the structural discontinuity caused by the demographic transition. Here we report on a new probabilistic approach that makes use of expert opinion on trends in fertility, mortality and migration, and on the 90 per cent uncertainty range of those trends in different parts of the world. We have used simulation techniques to derive probability distributions of population sizes and age structures for 13 regions of the world up to the year 2100. Among other things, we find that there is a probability of two-thirds that the world's population will not double in the twenty-first century.

Age Distribution↗
PubMed1997

[Biomarkers of hepatotoxic effects: their usefulness in occupational medicine].

Medical screening and the resultant monitoring of health effects induced by hepatotoxins present in workplaces become of still greater importance in the assessment of occupational health and safety. Health effects of occupational and nonoccupational hepatotoxic factors may be acute, subacute or chronic. Laboratory tests (biomarkers) used in screening for detection of asymptomatic damages of the liver should satisfy the following three criteria: 1. they should provide positive or negative predictive information, namely the information about possible development of clinically evident hepatopathy; 2. they should be very sensitive and specific in order to ensure a correct identification of the developing disease; and 3. they should provide information which of clinical biomarkers should be applied subsequently in order to confirm and facilitate the diagnosis of hepatopathy related to exposure to occupational hepatotoxins or to eliminate such a relationship. It should be also remembered that for assessing disorders in hepatic functions those biomarkers should be selected which are most effective in identifying both persons with hepatopathy induced by environmental hepatotoxins and those who are free from the liver damages. It should be stressed that to date none of the existing biomarkers is sensitive and specific enough to assess alone all the functional systems of the liver.

Air Pollutants, Occupational↗
PubMed1997

[Biomarkers in diagnosis of kidney diseases caused by chemical toxins].

As yet there has been no evidence produced that nephrotoxic chemicals damage nephron in sites, characteristic of a given toxin. A number of nephrotoxic effects result rather from changes induced by these substances mostly in the peripheral circulatory system than from a direct effect of chemical toxin on the kidneys. In many cases the morbid process in the kidneys does not emerge until a considerable number of nephrons is already damaged. Therefore, it is essential that doctors, attending patients exposed to nephrotoxins, have at their disposal, during periodical examinations, appropriate laboratory tests (biomarkers) able to detect subclinical forms of chemical damage of the kidneys. These biomarkers should also help to identify which of the functional parts of the kidneys have been damaged. It seems that determination of protein excreted with urine is one of the best biomarkers most frequently used to detect the dysfunction of renal glomerulus. It is recommended that the relationship between urine concentration of total protein and urine concentration of creatinine be determined. In the group of biomarkers of tubule dysfunction the measurement of substances usually reabsorbed from glomal filtrate (low-molecular protein) in proximal tubule or determination of enzymes' activity in urine (e.g. N-acetylo-glucosoaminidase) and those cellular components which are not excreted with normal urine are recommended. In the assessment of distal renal tubule dysfunction it is advised to examine urine osmolarity and/or determination of Thamm-Horsfall glycoprotein.

Biomarkers↗
PubMed1997

Determination of tissue polypeptide antigens (TPA) and carcinoembryonic antigen (CEA) in serum: its value in the preliminary cancer risk assessment in asbestos exposed workers.

Seeking the changes at the cellular level or at the level of cellular metabolism products, present in the biological fluids, in order to detect early stages of the carcinogenic process is an essential step in preventing cancer development among asbestos exposed workers. Carcinogenic biomarkers such as tissue polypeptide antigens (TPA) and carcinoembryonic antigen (CEA) were found very useful in this attempt. The objective of this work was to identify individuals at critical cancer risk in the population of workers exposed to asbestos and to evaluate the value of TPA and CEA determinations for this particular purpose. The study was carried out in the group of workers exposed to asbestos (n = 274). Age, exposure duration, smoking habits and the kind of job performed, were considered in the analysis of the results. To sum up, it should be concluded that in 22 persons exposed to asbestos TPA values exceeded the cut off concentrations, established on the basis of the studies performed in the control group, and CEA value accounted for 10 ng/lm. Statistically significant differences in the percentage of TPA increased values between two groups under study were indicated. Such a relationship did not apply to CEA. In the exposed group, an evident effect of the age and exposure duration on the number of persons with TPA concentrations above the cut off, was also revealed. These changes show a growing tendency and statistical significance for TPA only. Smoking had a great impact on the occurrence of TPA increased concentrations. Three kinds of jobs were considered: operation of the production line, white collar workers and miscellaneous'. The significant differences in TPA concentrations between the operators and miscellaneous, and between white collar workers and miscellaneous were found. Therefore, it may be concluded that a similar percentage of TPA increased values was observed in the group of operators and white collar workers. The study allowed to identify, among those exposed to asbestos, 22 persons who should be covered with target medical care. It also indicated that TPA determination was more useful than that of CEA in this kind of investigations.

Adult↗
PubMed1996

Conditional expression of N-myc in human neuroblastoma cells increases expression of alpha-prothymosin and ornithine decarboxylase and accelerates progression into S-phase early after mitogenic stimulation of quiescent cells.

To elucidate the contribution of the N-Myc protein to neuroblastomas we have used a synthetic inducible expression system on the basis of the tetracycline repressor of E coli to reversibly express N-myc in a human neuroblastoma cell line in which expression of endogenous N-myc is barely detectable. Like the c-Myc protein, N-Myc up-regulates the expression of both alpha-prothymosin and ornithine decarboxylase. Induction of N-myc increases both the rate of DNA-synthesis and the proliferation rate, and shortens the G1 phase of the cell cycle. A comparison of cell populations in which the presence of N-Myc protein was restricted to different parts of G(zero)/G1 revealed that N-Myc is rate-limiting for cell cycle progression during the first 5 h after serum stimulation of quiescent cells providing direct evidence that Myc-proteins act early after mitogenic stimulation of quiescent cells.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1996

Evaluation of psychotherapy. Efficacy, effectiveness, and patient progress.

Treatment-focused research is concerned with the establishment of the comparative efficacy and effectiveness of clinical interventions, aggregated over groups of patients. The authors introduce and illustrate a new paradigm-patient-focused research-that is concerned with the monitoring of an individual's progress over the course of treatment and the feedback of this information to the practitioner, supervisor, or case manager.

Adult↗
PubMed1996

[Exposure to asbestos and levels of selected tumor biomarkers].

Occupational exposure to asbestos, a recognised carcinogen, poses a risk for such diseases as asbestosis, lung cancer and mesothelioma. It is thought that asbestos fibres may damage microphages which undergo neoplastic transformation as well as fibroblast, while partial phagocytosis may generate free oxygenic radicals which induce cellular peroxidase and damage macromolecules. A search for cellular changes or changes in cellular metabolism products, present in biological fluids, in order to detect early stages of a neoplastic process is an important factor in the prophylaxis of workers exposed to asbestos. Neoplastic biomarkers such as tissue polypeptide antigen (TPA) or carcinoembryonic antigen (CEA) are now used for this purpose. The aim of the work was to identify workers exposed to asbestos in the population, especially high risk groups neoplastic diseases and to evaluate the usefulness of TPA and CEA determinations. The study covered a group of asbestos exposed workers (n = 4000 and the control group of workers (n = 135) nonexposed to any toxic factor at work. Age, exposure time, smoking habits and workpost characteristics were taken into consideration in the analysis of the results. It was revealed that in 38 persons exposed to asbestos, TPA values were above the concentration limit set on the basis of studies carried out in the control group, and elevated CEA values applied to 13 persons. Significant differences between groups under study were found in the proportion of pathological TPA values. Such a relationship was not observed in regard to CEA values. In the exposed group the results also indicated an evident effect of age and exposure time on the number of persons with TPA values above concentration limit. There is a growing tendency in those changes but only in regard to TPA values. The effect of smoking on the frequency of pathological TPA values was also clear-cut in workers exposed to asbestos. Taking into account three types of employment: blue collar workers, white collar workers and other personnel, the analysis indicated significant differences in TPA values between blue collar workers and other personnel; and between white collar workers and other personnel. This means a similar percentage of pathological TPA values in the group of blue collar and white collar workers. The study carried out allowed to identify persons exposed to asbestos who should be covered with targeted medical care. They also proved that TPA biomarker is better than CEA one for this kind of studies.

Adult↗
PubMed1996

[Biomarkers of neurotoxic effects induced by environmental chemicals].

Biological monitoring of neurotoxic effects induced by environmental chemicals covers a very broad spectrum of measurements beginning with molecular, subcellular and cellular changes through neurophysiological and neurobehavioral ones. For many years epidemiological studies had employed almost entirely neurophysiological and neurobehavioural ones. For many years epidemiological studies had employed almost entirely neurophysiological and neurobehavioural tests in the assessment of the magnitude and effects of exposure to neurotoxins. Only in the recent past, due to paramount advances in experimental biochemical toxicology, the application of biochemical tests-biomarkers of exposure, health effects and susceptibility-in neuroepidemiological studies became realistic. That was also associated with the detection of molecular targets for neurotoxins and the explanation of mechanisms of their effect. Exposure biomarkers define an absorbed dose and provide a quantitative measurement of adducts produced by neurotoxin (or its metabolite) or products of interaction with endogenic substances, for example, with DNA or enzymatic proteins. Biomarkers of health effects provide information on changes in the nervous system which occurred in its different sections: organic, tissular, cellular, subcellular and molecular, due to exposure to neurotoxic agents. Biomarkers of susceptibility inform that in a given person or population adverse health effects may be expected in the nervous system in the case of lower or higher exposure to a neurotoxic agent. They may prove useful in assessing the probability of progress in the disease of the nervous system due to exposure to environmental neurotoxins. They are measurable indicators of the nervous system biological factors which occur prior to exposure and are genetically determined or acquired. The latter may result from past diseases of the nervous system or earlier exposure to neurotoxic agents. The fact that the targeted cell-the nervous tissue-cannot be explored directly is one of the most important obstacles which still hinders the monitoring of neurotoxic effects by means of biochemical tests. On account of this limitation, in order to identify and characterise neurotoxic features, it is necessary to use those biochemical parameters which exist in easily accessible peripheral tissues, and which correspond with the parameters of the nervous tissue. It has thus far been found that biochemical markers present in the morphotic elements of peripheral blood (plates, leucocytes, erythrocytes) can be used as measurable, substitutive indicators of damages, dysfunctions and interactions in the nervous system caused by environmental neurotoxins.

Biomarkers↗
PubMed1996

[Genetic examinations in health care].

Genes are one of the most important indicators of disease incidence. Almost each diseases results from incorrect function of one or more genes. The disclosure of disease genetically conditioned depends, in many cases, on the effect of a broad spectrum of different environmental factors. Screening tests for carries of defective genes play a key role in the detection of risk for genetically conditioned diseases. Screening tests carried out for many years yielded a very diversified results. Some of them, for example, the screening test for the gene responsible for Tay-Sachs disease, produced good results, whereas results of other tests, like the test for the gene responsible for crescent anaemia, proved to be unsatisfactory. Among genetically conditioned diseases, neoplastic diseases are the subject of particular interest. It is already known that these diseases may be attributed to the accumulation of genetic errors in a normal cell, and that this phenomena applies to certain categories of genes. An analysis of genetic material of persons from the families with higher cancer incidence revealed the relationship between cancer and inheritance of some defective genes. Nevertheless, it should be stressed that the development of cancer is not definitely foregone even if genetic features of cancer disease are detected in a given person. The presence of such features only indicates an inborn or acquired defect (as a result of mutation) that predisposes him/her to illness. A great progress in molecular oncology made during the last years and the development of genetic maps relevant to neoplastic diseases should contribute to the detection of such genetic markers which could facilitate the identification of persons with a higher risk for neoplastic diseases and allow to take relevant preventive measures in due time.

Chromosome Mapping↗
PubMed1996

[Oncoproteins and anti-oncoproteins in blood serum as biomarkers of early health effects induced by occupational and environmental carcinogens].

Over a whole life-span a genetic machinery of human cells is exposed to carcinogenic effect of various chemical, physical and biological factors leading to cellular changes in the genome like point mutation and translocation or amplification of genes. Together with growing an ageing of the human organism, the number and heterogeneity of mutated cells increase. Thus, the presence or absence of the neoplastic process may depend on the length of life, efficiency of the immunological system, cumulation of adverse affects of environmental factors or inherited susceptibility to a disease. There is no doubt that neoplasms which develop due to inheritance of different genetic defects or due to direct environmental effect progress in line with similar mutations, resulting finally in the genome destabilisation and disturbances in the balance between proliferation and differentiation processes. The knowledge as to how far environmental carcinogens affect cellular genome is still limited. Nevertheless, data collected to date help to understand the mechanisms by which environmental carcinogens may initiate the process of transforming normal cells into neoplastic ones. It is most likely that activation of some oncoproteins and deactivation of some suppressive genes and related qualitative and quantitative changes in oncoproteins and anti-oncoproteins participating in the growth control and cellular division, are the essential mechanisms which are involved in this process. The discovery that activation of oncoproteins and related emergence of oncoprotein in cells, increased in the number of changed, can be monitored in easily available biological fluids, such as blood or urine, has become of great importance for occupational medicine and environmental health. That has provided new diagnostic measures for evaluating carcinogenic effects of the working and living environments. The fact, that the emergence of oncoproteins in biological fluids may precede by many months or even years clinical manifestations of neoplastic disease should greatly contribute to undertaking more effective preventive measures.

Antibodies, Neoplasm↗
PubMed1995

[Oxidative stress as a basic mechanism of the carcinogenic effect of man made mineral fibers on the human body].

Man made mineral fibres have been recently introduced into industry as asbestos exchangers due to their much less harmful effect on workers' health. However, in 1988 IARC classified such mineral fibres as glass wool, rock wool and slag wool as probably carcinogenic for a man. The mechanism how MMMF may induce the carcinogenic process remains still unclear. It is assumed that the involvement of these fibres in the production of free oxygenic radicals is one of the most important factors contributing to the initiation of this process by MMMF. In the condition where free oxygenic radicals are produced very fast, the cell is exposed to an oxidative stress. The DNA damage is an important consequence of the oxidative stress. New oxygenic radicals may modify DNA and lead to mutation and finally they may contribute to the occurrence of neoplastic cells. OH is an oxygenic radical which most often damages DNA. It was also indicated that MMMF contributes to the increase of the number and activity of neutrophilic granulocytes and macrophages. The appearance of MMMF fraction in granulocyte results in an increased production of free oxygenic radicals which may damage DNA of epithelial cells. Experimental studies indicate that the production of free oxygenic radicals by neutrophilic granulocytes and macrophages activated by MMMF increases under the influence of chemicals embodied in tobacco smoke. The fibres when combined with tobacco smoke enlarge the number of DNA damages. Notwithstanding the information on a possible induction of a carcinogenic process by MMMF, epidemiological studies indicate that MMMF shows much less carcinogenic hazard than asbestos fibres.

Carcinogens↗
PubMed1995

Biomarkers used for the assessment of health hazards in populations living in the vicinity of communal and industrial waste dump sites.

The measure of individual hazard from exposure to environmental toxicants are the biomarkers which are indices of abnormalities within different biological systems that may be induced by hazardous agents of various chemical or biological nature. The biomarkers make it possible to "monitor" the processes within the organism from the moment of toxic agent penetration to the development of clinical symptoms. Biomarkers offer the possibility of early detection of phenomena which tend to be arranged in the sequence of pathogenic changes, usually not detectable by the conventional methods. Depending on the type of processes which accompany the effect of a specified harmful environmental agent on the human organism it may be determined with the aid of the biomarkers, which are then classified as exposure, health effect, and individual susceptibility. By integrating such concepts as exposure, health effect, and individual susceptibility, enhanced analysis of the problem of health risk in people exposed to environmental toxic agents has become possible.

Biomarkers↗
PubMed1995

[Glutathione S-transferase as a metabolic biomarker for predisposition to lung neoplasms induced by chemical carcinogens].

In the case of lung cancer induced by chemical carcinogens, cellular processes of metabolic activation and deactivation of these substances play a particular role. The involvement of glutathione--S-transferase in the process of deactivation of active metabolites draws special attention. Cellular activity of these enzymes is a significant factor which can define individual susceptibility to carcinogenic effect of occupational and environmental carcinogens. Glutathione--S-transferase catalyses the reaction of binding glutathione with a great number of pharmacologically active substances, including also those with genotoxic properties. These reactions protect cells against toxic and genotoxic effect of exo- and endogenous substances. They prevent among others, from producing adducts by genotoxic substances with macromolecules. Some of glutathione--S-transferases (the so-called ligands) act as proteins which bind and transport organic ligands in cells (bilirubin, steroid metabolites, bile acids). To date studies have not confirmed uni-vocally that low activity of glutathione--S-transferases be one of the reasons for an increased incidence of lung cancer. Observations of persons with phenotype of a low activity of glutathione--S-transferase (GSTM1-0) have indicated that the incidence of lung cancer is significantly higher among them than in persons with phenotype of normal activity of this enzyme. These observations, however, have not been confirmed by an analysis of relationship between the incidence of lung cancer and the genotype of low and normal activity of glutathione--S-transferase.

Biomarkers, Tumor↗