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W Lutz

Publications and source records attributed to W Lutz.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Metallothioneins as stressor proteins modulating the immune response].

Matallothioneins are a group of cellular proteins whose synthesis increases considerably in conditions of stressful reactions to harmful environmental factors, especially to heavy metals. They are considered to be proteins of intracellular activity whose specific effect on the metal-dependent enzymes is revealed within the cells, as well as proteins which regulate the transcription process. Metallothioneins released from cells to extracellular fluids, for example due to the damage of membrane, may disclose non-specific effect which usually does not occur. In such conditions, metallothioneins may also affect other cells of tissues and organs placed far away from targets of heavy metal. They also play an important role in the regulation of normal vital functions of the cells in the immune system. In numerous cases, because of their unique chemical structure and biological properties, metallothioneins perform the function of immunomodulators. In the majority of cases, the modulatory effect is favourable for the body as a whole. However, in some cases, this effect is negative, for example it hinders the removal of potentially neoplastic cells from the body.

Adjuvants, Immunologic↗
PubMed1999

Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation.

PURPOSE/OBJECTIVE: This study evaluates the dosimetric benefits and feasibility of a deep inspiration breath-hold (DIBH) technique in the treatment of lung tumors. The technique has two distinct features--deep inspiration, which reduces lung density, and breath-hold, which immobilizes lung tumors, thereby allowing for reduced margins. Both of these properties can potentially reduce the amount of normal lung tissue in the high-dose region, thus reducing morbidity and improving the possibility of dose escalation. METHODS AND MATERIALS: Five patients treated for non-small cell lung carcinoma (Stage IIA-IIIB) received computed tomography (CT) scans under 4 respiration conditions: free-breathing, DIBH, shallow inspiration breath-hold, and shallow expiration breath-hold. The free-breathing and DIBH scans were used to generate 3-dimensional conformal treatment plans for comparison, while the shallow inspiration and expiration scans determined the extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry, and for DIBH, modified slow vital capacity maneuvers. Planning target volumes (PTVs) for free-breathing plans included a margin for setup error (0.75 cm) plus a margin equal to the extent of tumor motion due to respiration (1-2 cm). Planning target volumes for DIBH plans included the same margin for setup error, with a reduced margin for residual uncertainty in tumor position (0.2-0.5 cm) as determined from repeat fluoroscopic movies. To simulate the effects of respiration-gated treatments and estimate the role of target immobilization alone (i.e., without the benefit of reduced lung density), a third plan is generated from the free-breathing scan using a PTV with the same margins as for DIBH plans. RESULTS: The treatment plan comparison suggests that, on average, the DIBH technique can reduce the volume of lung receiving more than 25 Gy by 30% compared to free-breathing plans, while respiration gating can reduce the volume by 18%. The DIBH maneuver was found to be highly reproducible, with intra breath-hold reproducibility of 1.0 (+/- 0.9) mm and inter breath-hold reproducibility of 2.5 (+/- 1.6) mm, as determined from diaphragm position. Patients were able to perform 10-13 breath-holds in one session, with a comfortable breath-hold duration of 12-16 s. CONCLUSION: Patients tolerate DIBH maneuvers well and can perform them in a highly reproducible fashion. Compared to conventional free-breathing treatment, the DIBH technique benefits from reduced margins, as a result of the suppressed target motion, as well as a decreased lung density; both contribute to moving normal lung tissue out of the high-dose region. Because less normal lung tissue is irradiated to high dose, the possibility for dose escalation is significantly improved.

Aged↗
PubMed1999

MycN sensitizes neuroblastoma cells for drug-induced apoptosis.

Amplification of the MYCN gene is found in a large proportion of neuroblastoma and considered as an adverse prognostic factor. To investigate the effect of ectopic MycN expression on the susceptibility of neuroblastoma cells to cytotoxic drugs we used a human neuroblastoma cell line harboring tetracycline-controlled expression of MycN. Neither conditional expression of MycN alone nor low drug concentrations triggered apoptosis. However, when acting in concert, MycN and cytotoxic drugs efficiently induced cell death. Apoptosis depended on mitochondrial permeability transition and activation of caspases, since the mitochondrion-specific inhibitor bongkrekic acid and the caspase inhibitor zVAD-fmk almost completely abrogated apoptosis. Loss of mitochondrial transmembrane potential and release of cytochrome c from mitochondria preceded activation of caspase-8 and caspase-3 and cleavage of PARP. CD95 expression was upregulated by treatment with cytotoxic drugs, while MycN cooperated with cytotoxic drugs to increase sensitivity to CD95-induced apoptosis and enhancing CD95-L expression. MycN overexpression and cytotoxic drugs also synergized to induce p53 and Bax protein expression, while Bcl-2 and Bcl-X(L) protein levels remained unchanged. Since amplification of MYCN is usually associated with a poor prognosis, these findings suggest that dysfunctions in apoptosis pathways may be a mechanism by which MycN-induced apoptosis of neuroblastoma cells is inhibited.

Apoptosis↗
PubMed1999

Patient profiling: an application of random coefficient regression models to depicting the response of a patient to outpatient psychotherapy.

Adaptive treatment planning is a dynamic process that is dependent on valid, systematic assessments. The dosage and phase models provide theoretical bases for the development of such "patient-focused" information. Given an underlying mathematical regularity to the recovery process, growth modeling techniques can be used to determine an expected treatment response for every patient. By mapping the patient's actual status against such an expected change trajectory, it is possible to address the most clinically relevant question, "Is this treatment working?"

Adult↗
PubMed1999

Predicting patients' responses to psychotherapy: are some more predictable than others?

Patient profiling predicts improvement across psychotherapy sessions on the basis of intake clinical characteristics. Patients completed questionnaires before their 1st session and at other points during treatment. After using hierarchical linear modeling to calculate expected courses of improvement, 1/2 of the sample was divided into 1 of 2 groups: those whose treatment responses across sessions matched or exceeded their expected courses (75% of the sample) and those whose responses failed to match expectations. A discriminant function analysis indicated that the groups could be differentiated on the basis of intake characteristics; that is, patients with higher discriminant scores were more likely than those with low discriminant scores to have responded to psychotherapy as predicted. Successful cross-validation of the predictor weights was performed with the other 1/2 of the sample.

Adult↗
PubMed1999

Down-regulation of endothelial cell growth inhibitors by enhanced MYCN oncogene expression in human neuroblastoma cells.

Recent evidence indicates that the genetic alterations of the multistage process of malignant transformation appear to activate tumor neovascularization by altering the balance between stimulators and inhibitors of angiogenesis. In the present study, we have attempted to define the effect of enhanced MYCN oncogene expression on the profile of endothelial cell growth modulators in neuroblastoma cells. We report here that conditioned medium of human neuroblastoma cells with normal MYCN expression contains three inhibitors of endothelial cell proliferation, which appear to be novel proteins as judged by their physicochemical, immunological and biological properties. All three inhibitors are diminished or become undetectable upon experimental increase of MYCN expression. Our results suggest that enhanced MYCN expression in human neuroblastoma cells alters the angiogenic balance by down-regulating endothelial cell growth inhibitors but leaving the expression of the stimulators unaffected. These data shed light on the molecular mechanisms linking the genetic changes of malignant transformation with initiation of tumor angiogenesis. Moreover, our observations might explain the poor prognosis of human neuroblastomas following MYCN oncogene amplification through initiation of angiogenesis and subsequent tumor growth and spread.

Cell Division↗
PubMed1999

Transcranial Doppler sonography guided by magnetic resonance angiography for improved monitoring of intracranial arteries.

Transcranial Doppler (TCD) sonography combines the advantages of real-time hemodynamic information, cost-effectiveness, and bedside application. However, measurements can be difficult to reproduce because the spatial resolution and the determination of insonation angles are limited. The purpose of this study was to use the high anatomic resolution of three-dimensional (3D) magnetic resonance angiography (MRA) images for the stereotactic guidance of TCD in order to improve the accuracy and reproducibility of TCD examinations. The MRA examinations were performed on a 1.5 T scanner using a 3D flow compensated gradient-echo sequence. A noninvasive stereotactic mask was used for image registration. The MRA data were then transferred to a personal computer. An infrared tracking system registered the position of the head and the ultrasound probe during TCD. This enabled the authors to superimpose a virtual ultrasound beam onto the MRA projections of the intracranial arteries displayed on the monitor of the personal computer. This allows the examiner to easily identify the insonated intracranial artery and displays the insonation angle. In volunteer examinations (n = 10), the accuracy and reproducibility for the localization of specific vessel segments was 2.48 mm for the middle cerebral artery and 2.81 mm for all insonated intracranial arteries (middle cerebral artery, anterior cerebral artery, internal carotid artery, and posterior cerebral artery). Without navigation the reproducibility of vessel segment insonation dropped to 4.7 mm for the middle cerebral artery and to 4.84 mm for all vessels. The authors conclude that 3D MRA, acquired as an initial procedure in patients with intracranial vascular disorders, can be used to provide stereotactic guidance for repeated TCD examinations. This facilitates the reproducible insonation of specific vessel segments.

Adult↗
PubMed1999

[Transcranial Doppler ultrasonography: stereotactically guided examinations using magnetic resonance angiography].

The accurate localization of specific intracranial blood vessels is a major difficulty with transcranial Doppler sonography (TCD). It was the purpose of this study to develop a system enabling stereotactic navigation during a TCD examination on the basis of high-resolution three-dimensional magnetic resonance angiographic (MRA) data. During TCD, the examiner is provided--on a computer screen--with a projected view of the respective intracranial vessel anatomy. With the aid of an optoelectronic localization system, the spatial orientation and localization of the US probe is determined in real time, and correlated with the patient's MRA data using a dedicated stereotactic mask. Subsequently, the US beam and the points of insonation are displayed on the screen overlaid on the vessel anatomy. In this way the examiner gains real time control of the localization of the respective intracranial vessel insonated. Points of insonation can be stored and recalled for follow-up examinations. In addition to the successful verification of the system, it was shown that, in comparison with conventional TCD, stereotactic navigation distinctly improves the reproducibility of repeat TCD examinations.

Humans↗
PubMed1999

Ischaemic heart disease as an effect of obesity-related metabolic disturbances.

Obesity results from excessive accumulation of fats in adipose tissue and constitutes one of the essential sources of increased incidence of some diseases harassing the highly industrialized and urbanized societies. Obesity-related metabolic disorders may be associated with the risk of circulatory diseases. The mechanism causing that obesity enhances the incidence of the metabolic disorders have not been explained to the full extent. Hyperinsulinaemia is one of effects of obesity and of the associated presence of excessive blood fatty acid levels. Overloading of the organism with fatty acids changes the function pancreatic beta cells. Insulin resistance and hyperglycaemia caused by high peripheral fatty acid levels trigger increased insulin secretion. Hyperinsulinaemia affects hepatic metabolism so as to make it hyperanabolic. Liver increases triacylglycerol and cholesterol synthesis and raises the rate of very low density lipoproteins (VLDL) secretion to the blood. Increased VLDL concentration contributes to increased LDL and is associated with reduced HDL cholesterol concentrations. Atherogenic dyslipidemia in obese people results, to a large extent, from increased VLDL secretion. Data collected heretofore point to an undoubtedly essential role of the adipose tissue in the pathogenesis of metabolic disorders in obese people. There are many causes of disturbed adipose tissue function which result in high blood fatty acid levels, excessive fat accumulation in other tissues and organs, or both. Another factor which may aggravate the metabolic disorders is the diet. It is worth noting that genetic determinants may cause that some individuals reveal a specified set of factors increasing the risk of ischaemic heart disease.

Cholesterol, HDL↗
PubMed1999

The biomarkers detecting early changes in the human organism exposed to occupational carcinogens.

Epidemiological studies and clinical data confirm that occupational exposure to carcinogenic agents plays an important role in cancer etiology. Recent tremendous progress in understanding of the mechanisms of carcinogenesis, and also introduction of new tests to recognize changes occurring in the exposed organism have made it possible for the occupational medicine to detect the earliest cancer stages which occur during the latent phase of the disease. Detecting pre-neoplastic changes which precede an overt form of cancer and identification of measurable indicators of those changes has been one of the fundamental aims of molecular biology research. Biomarkers may serve as a research tool which makes it possible to achieve this aim. Suitably selected biomarker sets can provide information on the extent of the exposure to carcinogenic agents (biomarkers of exposure), detect early changes produced by the agents in the exposed organism (biomarkers of effects), and identify people with particularly high cancer risk (biomarkers of susceptibility). It will soon be possible to use molecular biomarkers, capable of detecting increased cancer risk at the molecular level of cell structure, in prophylactic action intended to reduce cancer incidence. Molecular biomarkers are capable of recording very early health effects of exposure to carcinogens, thus making it possible to determine cancer risk at a very early stage of cancer development.

Carcinogens, Environmental↗
PubMed1998

MycN and IFNgamma cooperate in apoptosis of human neuroblastoma cells.

Neuroblastomas undergo spontaneous regression at an unusually high rate. The mechanisms are not clear, but apoptosis may be involved. A large proportion of neuroblastomas is characterized by amplification of MYCN. Using human neuroblastoma cells harbouring tetracycline controlled expression of MYCN we have analysed the role of the MycN protein and IFNgamma in cell death decision. Neither conditional expression of MYCN nor treatment with IFNgamma alone was sufficient to trigger cell death. However, when acting in concert MycN and IFNgamma efficiently triggered cell death, which was accompanied by DNA fragmentation and required caspase activity, two hallmarks of apoptosis. MycN and IFNgamma may cooperate along at least two different pathways. First, IFNgamma increased the CD95 cell surface expression while MycN enhanced the cellular susceptibility for the CD95 mediated death signal. Second, IFNgamma treatment induced expression of BAK mRNA while MycN and IFNgamma in combination increased the amount of Bax protein, another activator of apoptosis, without a concomitant increase in BAX mRNA. MycN also increased cell death in response to TRAIL and TNFalpha, suggesting that enforced MYCN expression in general increases the susceptibility of neuroblastoma cells towards a variety of death stimuli.

Antigens, CD↗
PubMed1998

Exploring individual change.

In the analysis of the impact of clinical interventions, the received wisdom has been that posttreatment scores, with pretreatment scores equated by random assignment or statistically partialed out, should be used to evaluate treatment outcomes. However, posttreatment scores are not generally more reliable than, nor equivalent to, change scores, even with pretreatment scores partialed out of both. Moreover, there are data-analytic methods that indicate how individual patients change, in terms of response curves over time, rather than indicate only how much groups change on the average. These methods take researchers back to the individual data that they ought to use for choosing the specific models of change to be used. To maximize relevance for clinical practice, the results of treatment research should always be reported at this most disaggregated or individual change level, as well as, when appropriate, at more aggregated statistical levels.

Data Interpretation, Statistical↗
PubMed1998

Biological and molecular characteristics of interleukin-5 and its receptor.

Interleukin-5 (IL5) is a T cell-derived cytokine involved in the pathogenesis of atopic diseases. It specifically controls the production, the activation and the localization of Eosinophils. The Eosinophils are the major cause of tissue damage resulting in the symptoms of asthma and related allergic disorders. T cells purified from bronchoalveolar lavage and peripheral blood of asthmatics secrete elevated amount of IL5. Therefore IL5 emerges to be an attractive target for the generation of new anti-allergic drugs. Agents which inhibit either the production or the activity of IL5 could be expected to ameliorate the pathological effects of the allergic response. A better understanding of the biology of IL5 and the regulation of its expression is, however, a prerequisite for the development of new therapeutic agents. This review covers the major biological, molecular and structural aspects of IL5 research since the identification of this cytokine ten years ago.

Eosinophils↗
PubMed1998

Determination of blood serum oncoprotein NEU and antioncoprotein p-53--molecular biomarkers in various types of occupational exposure.

Application of various diagnostic tests for occupational cancer risk monitoring is associated with the fact that gene mutations and changes in gene expression correspond to the earliest stages of carcinogenesis, namely early stages of the promotion process. The changes in protooncogenes and suppressor genes can be detected either at the genome level, at the level of transferring the genetic information from DNA to protein, or at the level of protein synthesis controlled by genes (oncogenes or antioncogenes). In the latter instance, as the concentrations of these proteins are considerably increased, their quantities in blood serum can be determined by the immunochemical methods. In our work, blood serum p-53 and NEU proteins were determined in 32 workers exposed to asbestos and in 57 workers exposed to PAHs. The proteins were also determined in 99 patients with overt cancer and in 47 controls. The data obtained in this work show positive values of oncoprotein NEU or antioncoprotein p-53 in 17.3% to 31.8% of workers exposed to PAHs or asbestos. The percentage of positive values for the examined proteins in the patients with overt cancer ranged from 12.5% to 42.5%. It should be noted that positive values of the oncoproteins detected in the biomaterial of the persons exposed do not mean that people must necessarily develop cancer, nevertheless the elevated values should be regarded as a warning and an implication for undertaking suitable preventive steps.

Adult↗
PubMed1998

[Use of hypoprothrombinemia provocation test for early diagnosis of liver disease caused by harmful environmental agents].

The aim of this work has been to assess the feasibility of using Prothrombin Time (PT) Assay before and after administration of Pelentan (Hypoprothrombinemia Provocation (HPP) Test) for early detection of subclinical toxic hepatic injuries. The proposed modification of PT Assay is based on the observation that people with slight hepatic injury receiving small doses of Pelentan (diethylcoumarol) display remarkably longer PT than healthy people receiving similar doses of the chemical. The test group comprised 37 people occupationally exposed to hepatotoxic agents, 85 males permanently abusing alcohol, while 24 clinically healthy people, not exposed occupationally to the toxic agents served as the control. In addition, 26 hepatitis B and/or C virus carriers were also examined. The results show that: 1. HPP test enables assessment of hepatic function in patients with suspected hepatic injury and in people permanently abusing alcohol; 2. low value of serum prothrombin index 24 h and 48 h after the administration of Pelentan is indicative of the positive result of the test; 3. HPP test provides more information on the functional condition of liver than single PT determination by the Quick assay.

Adult↗
PubMed1998

[Urinary cotinine as a biomarker of exposure to tobacco smoke].

Several markers are used to monitor active or passive exposure to tobacco smoke. They include measurements of carboxyhaemoglobin in the blood, carbon dioxide in the expired air, thiocyanates and nicotine in the saliva, plasma (serum) or urine. The determination of cotinine, the main nicotine metabolite, in biological fluids is a biomarker which finds still wider application. This metabolite can be determined in the urine and saliva and plasma. Cotinine, as a biomarker of exposure to tobacco smoke, is used in epidemiological studies aimed to find out to what extent the exposure to occupational harmful factors affects the workers' health. The application of this biomarker helped to classify workers more effectively into smokers and non-smokers, and to provide better conditions for finding out whether other non-occupational factors such as smoking do not confound the evaluation of health threats induced by work-related hazards.

Biomarkers↗