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Biomedical subjects

D Nowak

Publications and source records attributed to D Nowak.

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

Sensitization and lung function in workers occupationally exposed to natural thickening products.

BACKGROUND: Three workers engaged in the manufacture of natural thickener products (Cassia spp., guar, and tamarind flour) were occupationally sensitized to Cassia spp. Therefore, a cross-sectional study on the prevalence of sensitization among and respiratory health of the employees of this plant was conducted. METHODS AND RESULTS: Sixty-two workers (36 with high, 26 with low exposure) participated in the survey. Skin prick tests and specific IgE tests with extracts of these components revealed that 11.3% were sensitized to Cassia spp. and 9.7% to at least one species of storage mites, with a significantly higher portion of atopic subjects in the sensitized group. Overall, 55% of the subjects reported work-related symptoms (upper and lower airways, eyes, or skin). FVC % pred. was significantly lower in highly exposed workers, while RV % pred. and RV%TLC % pred. were significantly higher in this group. In the multivariate model, sensitization was not a risk factor for impairment of lung function. CONCLUSIONS: Dust exposure to flours may not only cause allergic sensitization but also induce chronic changes in lung function.

Adolescent↗
PubMed2000

The economic impact of smoking in Germany.

Smoking is a high-risk behaviour affecting health and economic welfare of society. Thus it is important to quantify the economic burden smoking places on social institutions in Germany. Approximately 33.4% of the male and 20.4% of the female population are current smokers. This study investigates the health care costs of smoking based on 1996 figures, focusing on the seven most frequent diseases associated with the inhalation of tobacco smoke: chronic obstructive pulmonary disease (COPD, international classification of diseases (ICD) 490-491); lung cancer (ICD 162); stroke (ICD 434-438); coronary artery disease (ICD 410-414); cancer of the mouth and larynx (ICD 140-149, 161) and artherosclerotic occlusive disease (ICD 440). A data search was carried out on MEDLINE, the German Institute for Medical Documentation and Information, and the Internet as well as in databases of health insurance companies and the German Federal institute of statistics. Direct and indirect costs were calculated separately. The results estimate the total smoking related health care costs (attributable fraction due to smoking) for COPD to be 5.471 billion EURO (73%), for lung cancer 2.593 billion EURO (89%), for cancer of the mouth and larynx 0.996 billion EURO (65%), for stroke 1.774 billion EURO (28%), for coronary artery disease 4.963 billion EURO (35%) and for atherosclerotic occlusive disease 0.761 billion EURO (28%). The economic burden of smoking related health care costs for Germany is 16.6 billion EURO. Smoking is therefore responsible for 47% of the overall costs of these diseases (35.2 billion EURO). In the view of the high costs for smoking, of which almost 50% are due to respiratory disease, pneumologists should enhance their effort in primary, secondary and tertiary prevention.

Arteriosclerosis↗
PubMed2000

Exposure to endotoxin or other bacterial components might protect against the development of atopy.

BACKGROUND: Several recent studies have shown that growing up on a farm confers significant protection against the development of atopy. These findings point particularly towards the importance of exposure to stable dust and farm animals. It has furthermore been reported that endotoxin, an intrinsic part of the outer membrane of gram negative bacteria, is abundant in environments where livestock and poultry is kept. The aim of this study was therefore to measure the level of environmental endotoxin exposure in homes of farmers' children, children with regular contact to livestock and control children with no contact to farm animals. METHODS: Eighty-four farming and nonfarming families were identified in rural areas in Southern Germany and Switzerland. Samples of settled and airborne dust were collected in stables, and of settled dust indoors from kitchen floors and the children's mattresses. Endotoxin concentrations were determined by a kinetic Limulus assay. RESULTS: Endotoxin concentrations were highest in stables of farming families, but were also significantly higher indoors in dust from kitchen floors (143 EU/mg vs 39 EU/mg, P < 0.001) and children's mattresses (49479 EU/m2 vs 9383 EU/m2, P < 0.001) as compared to control children from nonfarming families. In addition, endotoxin levels were also significantly higher in mattresses and dust from kitchen floors in households where children had regular contact to farm animals (38.6 EU/mg and 23340 EU/m2, respectively) as compared to control subjects. CONCLUSION: We propose that the level of environmental exposure to endotoxin and other bacterial wall components is an important protective determinant for the development of atopic diseases in childhood.

Adolescent↗
PubMed2000

Inhaled glucocorticosteroids decrease hydrogen peroxide level in expired air condensate in asthmatic patients.

H2O2 is elevated in the exhaled air condensate in several inflammatory disorders of the lung, including bronchial asthma, and thus may reflect inflammatory processes in the airways. Exhaled H2O2 may be used to guide the anti-inflammatory treatment of patients with asthma. Therefore in this study we analysed the effect of inhaled glucocorticosteroid beclomethasone for 4 weeks on H2O2 level in the exhaled air condensate. Seventeen asthmatics and 10 healthy subjects were included to the study. Eleven patients were given inhaled beclomethasone and six were given placebo (3M Health Care). In all patients pulmonary function tests were performed. H2O2 in the expired air condensate was measured spectrofluorimetically (homovanillic acid method). Inhaled beclomethasone significantly decreased H2O2 in the expired air condensate in the active-treatment group, with a fall from baseline on day 1 which remained on day 43 (follow-up) (P<0.05). Exhaled H2O2 in the active-treatment group was significantly lower than that in placebo group (P<0.05). A negative correlation between H2O2 and forced expiratory volume in 1 sec (FEV1) on day 29 was observed. The decrease in exhaled H2O2 in the active-treatment group was accompanied by an improvement in pulmonary function tests results. Inhaled glucocorticoids reduce the level of H2O2 in the expired air condensate of asthmatic patients over a 4-week period and this may reflect their anti-inflammatory activity in lung diseases.

Administration, Inhalation↗
PubMed2000

Comparison of hydrogen peroxide generation and the content of lipid peroxidation products in lung cancer tissue and pulmonary parenchyma.

Lipid peroxidation, as a well-known index of reactive oxygen species activity, not only in lung biochemistry, is an oxidative process associated with membrane lipid destruction. Also, the oxidative modification of nucleic acids by reactive oxygen species is of remarkable biological importance as it may contribute to malignant conversion, but its exact role in lung cancer biology is still not clear. Our study aimed to investigate the level of lipid peroxidation ex vivo in tumour tissue and lung parenchyma obtained from patients with lung cancer. Forty-two patients with lung cancer were enrolled into the study. During a surgical resection, tumour tissue and lung parenchyma were obtained and concentration of lipid peroxidation products, thiobarbituric acid-reactive substances and Schiff bases, and spontaneous generation of hydrogen peroxide, were measured. The concentration of thiobarbituric acid-reactive substances (P<0.001) in the tumour tissue was higher than that in lung parenchyma. In small cell lung cancer as well as in squamous cell carcinoma patients, a positive correlation between spontaneous generation of hydrogen peroxide in tumour tissue and clinical stage (r = 0.43; r = 0.46; respectively) was found. Our results prove enhanced lipid peroxidation in cancer tissue as compared with matched-lung parenchyma. In small cell lung cancer and squamous cell carcinoma patients, the high level of oxidative stress, expressed as a spontaneous generation of hydrogen peroxide in tumour tissue, was associated with clinical progression of tumour's stage.

Aged↗
PubMed2000

Lung function and work-related exposure in pig farmers with respiratory symptoms.

The present study was conducted to evaluate characteristics of pig houses that are associated with the development of respiratory morbidity in 100 swine producers with work-related respiratory symptoms. A standardized questionnaire for farm characteristics was used, and lung function was assessed immediately before and after feeding the pigs. Exposure to dust and endotoxin was determined by personal sampling. Among these farmers, baseline lung function results were shown to be negatively associated with duration of employment, number of pigs on the farm, manual feeding, and ventilation. The decrease in forced vital capacity and forced expiratory volume in 1 second over the feeding period was negatively correlated with air velocity, whereas respirable dust concentrations were shown to be significant predictors of maximal midexpiratory flow (MMEF25/75) decline. In conclusion, among symptomatic pig farmers, those with higher numbers of pigs and longer duration of employment are at highest risk for developing functional impairment.

Adult↗
PubMed2000

Lung function, biological monitoring, and biological effect monitoring of gemstone cutters exposed to beryls.

OBJECTIVES: Gemstone cutters are potentially exposed to various carcinogenic and fibrogenic metals such as chromium, nickel, aluminium, and beryllium, as well as to lead. Increased beryllium concentrations had been reported in the air of workplaces of beryl cutters in Idar-Oberstein, Germany. The aim of the survey was to study the excretion of beryllium in cutters and grinders with occupational exposure to beryls--for example, aquamarines and emeralds--to examine the prevalence of beryllium sensitisation with the beryllium lymphocyte transformation test (BeLT), to examine the prevalence of lung disease induced by beryllium, to describe the internal load of the respective metals relative to work process, and to screen for genotoxic effects in this particular profession. METHODS: In a cross sectional investigation, 57 out of 100 gemstone cutters working in 12 factories in Idar-Oberstein with occupational exposure to beryls underwent medical examinations, a chest radiograph, lung function testing (spirometry, airway resistance with the interrupter technique), and biological monitoring, including measurements of aluminium, chromium, and nickel in urine as well as lead in blood. Beryllium in urine was measured with a newly developed direct electrothermal atomic absorption spectroscopy technique with a measurement limit of 0.06 microgram/l. Also, cytogenetic tests (rates of micronuclei and sister chromatid exchange), and a BeLT were performed. Airborne concentrations of beryllium were measured in three factories. As no adequate local control group was available, the cutters were categorised into those with an exposure to beryls of > 4 hours/week (group A) and < or = 4 hours/week (group B). RESULTS: Clinical, radiological, or spirometric abnormalities indicating pneumoconiosis were detected in none of the gemstone cutters. Metal concentrations in biological material were far below the respective biological limit values, and beryllium in urine was only measurable in subjects of group A. Cytogenetic investigations showed normal values which were independent of the duration of beryllium exposure. In one subject, the BeLT was positive. Beryllium stimulation indices were significantly higher in subjects with detectable beryllium in the urine than in those with beryllium concentrations below the detection limit (p < 0.05). In one factory, two out of four measurements of airborne beryllium concentrations were well above the German threshold limit value of 2 micrograms/m3 (twofold and 10-fold), and all gemstone cutters working in this factory had measurable beryllium concentrations in urine. CONCLUSION: No adverse clinical health effects were found in this cross sectional investigation of gemstone cutters working with beryls. However, an improvement in workplace hygiene is recommended, accompanied by biological monitoring of beryllium in urine.

Adult↗
PubMed2000

Respiratory symptoms of obstructive lung disease in European crop farmers.

Crop farming as a risk factor for respiratory symptoms of obstructive lung disease was assessed. Random samples of crop farmers from four European countries were studied following a cross-sectional design. A questionnaire on respiratory symptoms and occupation was administered to determine prevalences, and the roles of the various crops as risk factors for respiratory symptoms were assessed through logistic regression modeling. The 4,793 crop farmers included in the study (response rate: 85.3%) reported the following respiratory symptoms: wheezing (14.9%), asthma (3.3%), nasal allergy (14.4%), chronic phlegm (12.4%), organic dust toxic syndrome (ODTS) (15.2%), and symptoms at work (22.0%). In the multivariate analysis, adjusting for age, sex, smoking, country, and exposure to other plants or livestock, flower growing was a risk factor for asthma (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.1-3.9) and cultivating oil plants was associated with ODTS (OR 1.5, 95% CI 1.3-1.9), symptoms at work (OR 1.4, 95% CI 1.2- 1.7), and chronic phlegm (OR 1.3, 95% CI 1.1-1.6). Working inside greenhouses was a marginal risk factor for asthma (OR 2.1, 95% CI 0.9-4.5). We conclude that flower and oil plant production is associated with increased risk of respiratory symptoms in European crop farmers.

Adult↗
PubMed2000

Methimazole protection against oxidative stress induced by hyperthyroidism in Graves disease.

OBJECTIVE: To examine the dynamics of oxidative stress in patients with hyperthyroidism before and during the treatment with methimazole using the measurement of conjugated dienes, malondialdehyde, and Schiff bases in blood serum. METHODS: In eight female patients with diagnosed Graves disease and 8 healthy control subjects (7 females and one male) several parameters of oxidative stress (the level of conjugated dienes [CD], malondialdehyde [MDA] and Schiff bases [SB]) were estimated before and during the treatment with methimazole (Metizol -POLFA) as well as by hormonal and immunological tests. In addition, serum levels of TSH, free thyroxine (FT4), free triiodothyronine (FT3), antibodies against thyroperoxidase (anti-TPO) and thyroglobulin (anti-Tg) and low density lipoprotein-cholesterol fraction (LDL-Ch) were estimated. RESULTS: We observed increased concentrations of free thyroxine (FT4) and free triiodothyronine (FT3), as well as of antithyroperoxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies. At the same time, TSH level was significantly suppressed. The concentrations of thyroid hormones and of TSH normalised after the methimazole treatment. The examined parameters, i.e., CD, MDA, and SB, were evaluated as proportions of each of them to the level of low density lipoproteins-cholesterol fraction (LDL-Ch). This fraction of cholesterol contains many polyunsaturated fatty acids, being a substrate for the peroxidation of lipids. Additionally, the CD/MDA ratio was calculated. CONCLUSIONS: The increase of the CD/LDL ratio in Graves hyperthyroidism and its normalisation in the course of the treatment with methimazole suggests that the drug can be protective against the oxidative stress induced by overproduction of thyroid hormones. The ratio of CD/MDA decreased in all the patients, as compared to the control group, showing a high speed of lipid peroxidation.

Antithyroid Agents↗
PubMed1999

Studies on the genotoxic effects of aminophenazines using two cellular models and three different methods.

This paper presents studies on the genotoxicity of two aminophenazines: 2,3-diaminophenazine (DAP) and 2-amino-3-hydroxyphenazine (AHP). The genotoxic activities of these compounds were evaluated with human lymphocytes using the alkaline single cell gel electrophoresis (SCGE) assay and two cytogenetic assays (chromosome aberrations (CA) and sister chromatid exchange (SCE) analysis). Results show that these chemicals elicited an increase in DNA and chromosomal damage under the studied ranges of concentration. Concentration-response curves were similar and there was a positive correlation between the damage observed at the DNA and chromosomal levels. DAP was more genotoxic than AHP and this agreed with the genotoxic potencies reported in bacterial systems.

Chromosome Aberrations↗
PubMed1999

Work-related respiratory disorders and farming characteristics among cattle farmers in Northern Germany.

BACKGROUND: The aim of this cross-sectional study was to investigate the prevalence of respiratory symptoms among Northern German farmers in relation to cattle farming characteristics. METHODS: 1735 farmers were visited on their farms and were interviewed using a standardized questionnaire on work-related respiratory symptoms and farming details. RESULTS: 84.6% of the farmers were cattle farmers. The prevalence of work-related respiratory symptoms was 40.3%. In a multiple logistic regression model adjusting for response rate, age, gender, and smoking habits, work-related respiratory symptoms were shown to be significantly associated with the ventilation of the cattle house (OR (ventilation via the wall): 0.57), feeding management (OR (feeding once daily): 0.53), and plant crop (OR: 0. 75). Farmers, living inland, showed a significant higher prevalence of work-related respiratory symptoms (OR: 1.34). CONCLUSIONS: The use of ventilation via the wall might be recommended for new cattle houses in regions with warm winters.

Age Factors↗
PubMed1999

N-acetylcysteine and ambroxol inhibit endotoxin-induced phagocyte accumulation in rat lungs.

UNLABELLED: We have investigated whether pretreatment with N-acetylcysteine (NAC) and/or ambroxol (Amb), drugs known as reactive oxygen species (ROS) scavengers, would minimize lipopolysaccharide (LPS)-induced leucocyte accumulation in rat lung microvasculature and protect lungs from damage and the effect of these drugs on chemotactic peptide (fMLP)-induced chemiluminescence of human polymorphonuclear leukocytes (PMNs). Animals were injected ip with NAC (27.6 mg/kg, n=8), ambroxol (70 mg/kg, n=8), combination NAC+ambroxol (n=8), or 1 ml buffer alone (n=8), once a day for 3 consecutive days. Then animals were injected with LPS (17 mg/kg), and killed 3 h later. In each of another four groups eight rats were used as a control, and received the same drug treatment but LPS was replaced with 0.9% NaCl. PMNs and macrophages (Ms) were counted in histologic slides of lung tissue. Using computer image analysis we measured the area of alveolar profiles. Luminol-enhanced chemiluminescence was measured in PMNs suspensions obtained from healthy volunteers. Chemiluminescence intensity was measured in resting and fMLP-stimulated cells, and compared between cells incubated with Amb, NAC or distilled water. We observed significant differences in the number of PMNs and Ms, alveolar profile area between control and LPS-treated animals (P<0.01). PMNs and Ms were numerous in lungs of LPS-administered animals (PMNs: Median (M)=137.5 per 6 high power fields range (r)=54.0; Ms: M=123.0 r=11.0), less numerous in ambroxol-treated group (PMNs: M=101.5 r=32.0 and Ms:53.5 r=36.0), not abundant in NAC (PMNs:M=56.0 r=28.0 and Ms:M=20.5 r=13.0) and in NAC+ambroxol treated rats (PMNs:M=53.5 r=21.0 and Ms:M=29.0 r=9.0), and rare in LPS+drugs-untreated control group (PMNs:M=40.5 r=19.0 and Ms:M=18.5 r=15.0). Chemiluminescence assay revealed that 100 micro;M ambroxol stimulated fMLP-induced PMNs chemiluminescence and NAC of the same concentration had no significant effect. CONCLUSION: In our experiment we showed that pretreatment with NAC and ambroxol may inhibit phagocyte influx to rat lung and may protect it from damage. We also revealed that NAC at dose 27.6 mg/kg has stronger protective properties than ambroxol at dose 70 mg/kg and this may result from enhancing effect of ambroxol on fMLP-provoked PMNs chemiluminescence.

Acetylcysteine↗
PubMed1999

Grip forces exerted against stationary held objects during gravity changes.

In the present study, grip forces exerted against a stationary held object were recorded during parabolic flights. Such flight maneuvers induce changes of gravity with two periods of hypergravity, associated with a doubling of normal terrestrial gravity, and a 20 s period of microgravity. Accordingly, the object's weight changed from being twice as heavy as normally experienced and weightless. Grip-force recordings demonstrated that force control was seriously disturbed only during the first experience of hyper- and microgravity, with the grip forces being exceedingly high and yielding irregular fluctuations. Thereafter, however, grip force traces were smooth, the force level was scaled to the object's weight under normal and high-G conditions, and the grip force changed in parallel with the weight during the transitions between hyper- and microgravity. In addition, during weightlessness, when virtually no force was necessary to stabilize the object, a low force was established, which obviously represented a reasonable safety margin for preventing possible perturbations. Thus, all relevant aspects of grip-force control observed under normal gravity conditions were preserved during gravity changes induced by parabolic flights. Hence, grip-force control mechanisms were able to cope with hyper- and microgravity, either by incorporating relevant receptor signals, such as those originating from cutaneous mechanoreceptors, or by adequately including perceived gravity signals into control programs. However, the adaptation to the uncommon gravity conditions was not complete following the first experience; finer tuning of the control system to both hyper- and microgravity continued over the measurement interval, presumably with a longer observation period being necessary before a stable performance can be reached.

Adult↗
PubMed1999

Respiratory health and fluoride exposure in different parts of the modern primary aluminum industry.

OBJECTIVE: The aim of this cross-sectional study was to investigate possible acute and long-term respiratory health effects of work at different working places in the primary aluminum industry. METHOD: A cross-sectional study was carried out on 78 potroom workers, 24 foundry workers, and 45 carbon-plant workers (n = 147, exposed group), and 56 control workers (watchmen, craftsmen, office workers, laboratory employees) of a modern German prebake aluminum plant. The survey consisted of pre- and postshift spirometric and urinary fluoride measurements. RESULTS: Potroom workers had significantly lower preshift results with regard to forced vital capacity (FVC, 99. 5% versus the 107.2% predicted; P < 0.05) and peak expiratory flow (PEF, 85.2% versus the 98.4% predicted; P < 0.01) as compared with controls. In a multiple regression model a small but significant negative correlation was found between postshift urinary fluoride concentrations and FVC, FEV(1), and PEF. Across-shift spirometric changes were observed only in FVC among carbon-plant workers (103.0 +/- 13.3% predicted preshift value versus 101.2 +/- 13.6% predicted postshift value; P < 0.05). CONCLUSIONS: The results suggest that lung function impairment in the modern primary aluminum industry may be only partly due to fluoride exposure and that working in aluminum carbon plants may cause acute lung function changes.

Adult↗
PubMed1999

Increased serum concentrations of conjugated diens and malondialdehyde in patients with pulmonary tuberculosis.

During pulmonary inflammation increased amounts of reactive oxygen species (ROS) and reactive nitrogen intermediates (RNI) are produced as a consequence of phagocyte respiratory burst. One of the manifestation of these free radical-mediated processes is lipid peroxidation (LP). The aim of our study was to assess the concentration of lipid peroxidation products (LPPs), conjugated diens (CD) and malondialdehyde (MDA), in patients with active TB. Forty-two patients were enrolled into the study. Half (group I) had advanced TB and were sputum smear-positive. The remainder (group II) had only small radiographical changes and were sputum smear-negative. Serum concentrations of CD and MDA were measured at days 0, 7, 14 and 28 in group I and day 0 in group II. We found that in all patients with active TB CCD (1.0 +/- 0.05A233) and CMDA (2.01 +/- 0.16 nmol dl-1) were significantly elevated compared to healthy controls (0.67 +/- 0.03A233 and 1.36 +/- 0.08 nmol dl-1, respectively) (P < 0.001). The highest levels of LPPs were in patients with advanced TB. These concentrations were stable during the first month of anti-tuberculous therapy. Our data indicated that, as in bacterial pneumonia, LPPs were enhanced in active TB. The levels of LPPs depended on the form of the disease as they were higher in subjects with advanced disease than in those with only small radiographical changes. Further studies are needed to assess the role of antioxidants as adjuvant therapy in patients with pulmonary TB.

Biomarkers↗
PubMed1999

Increased content of thiobarbituric acid-reactive substances and hydrogen peroxide in the expired breath condensate of patients with stable chronic obstructive pulmonary disease: no significant effect of cigarette smoking.

The imbalance between oxidants and antioxidants is known to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoking is the most frequent factor responsible for development of COPD by leading to oxidant overload in the lower airways, due to presence of its own oxidants and to recruitment and activation of pulmonary phagocytes. We aimed to determine whether (1) patients with stable COPD have higher thiobarbituric acid-reactive substances (TBARs, an end-product of lipid peroxidation) and H2O2 levels in expired breath condensate than healthy subjects who have never smoked; (2) COPD subjects who are current smokers exhale more TBARs and H2O2 than COPD ex-smokers and those who have never smoked; and (3) concentration of TBARs correlates with H2O2 levels in the breath condensate of COPD patients. The TBAR and H2O2 content in expired breath condensate of 17 healthy nonsmoking subjects and 44 patients (11 current smokers, 20 ex-smokers and 13 who had never smoked) with stable COPD [forced expiratory volume in 1 s (FEV1) 63.3 +/- 16.3% and FEV1 reversibility 5.2 +/- 4.3% predicted value] was measured spectrofluorimetrically by the thiobarbituric acid and homovanillic acid methods, respectively. The mean concentrations of TBARs and H2O2 in the expired breath condensate of COPD subjects were 12 (0.48-0.86 microM vs. 0.04 +/- 0.14 microM; P < 0.05) and 10 times (0.48 +/- 0.67 microM vs. 0.05 +/- 0.07 microM; P < 0.005) higher than in healthy controls. Current smokers with COPD did not exhale more H2O2 than COPD ex-smokers and those who had never smoked. TBARs levels shared only a tendency to be higher in the breath condensate of smoking COPD subjects than in that of ex-smokers (0.92 +/- 1.49 microM vs. 0.35 +/- 0.44 microM) and of COPD subjects who had never smoked (0.92 +/- 1.49 microM vs. 0.30 +/- 0.53 microM). No correlation was found between TBAR and H2O2 levels in the whole COPD group. These variables did not correlate with cigarette smoking status and the time from smoking cessation. Subjects with stable COPD exhibit increased lipid peroxidation and H2O2 generation in the airways. Current cigarette smoking does not distinguish COPD subjects with respect to TBARs and H2O2 exhalation.

Antioxidants↗
PubMed1999

Variations of p53 in cultured fibroblasts of patients with lung cancer who have a presumed genetic predisposition.

The authors studied cultured skin fibroblasts of 64 patients with lung cancer for constitutive mutations of the p53 tumor suppressor gene by using polymerase chain reaction and single-strand conformation polymorphism covering the entire coding region. The patients were considered to be genetically predisposed because lung cancer had developed in 25 of them before age 46 and because 42 of them had at least one first-degree relative with lung cancer. One mutation was detected at position 235 coding for serine instead of asparagine in the conserved DNA binding domain. The Pro/Pro genotype at codon 72 of p53, considered to harbor an increased risk for lung cancer, could not be detected with increased frequency in this study's patients. From these data, the authors conclude that constitutive variations of the p53 gene do not represent a major genetic determinant for lung cancer.

Adult↗