[Breathing: Ambient Air Pollution and Health - Part III]. / Atmen: Luftschadstoffe und Gesundheit ­ Teil III.

The third part of the DGP statement introduces the current body of knowledge on less studied health outcomes associated with exposure to ambient air pollution: the negative impact on metabolism leading to impaired glucose tolerance and diabetes as well as contribution to the development of neurodegenerative disorders and delayed cognitive function in children. Furthermore, prenatal exposure and adverse effects on mother and child are addressed. Finally, the currently discussed biological mechanisms underlying various health effects associated with exposure to air pollution are described.Differing, but often complementary biological mechanisms create the basis for the diverse health outcomes caused by air pollution. Oxidative stress and a subclinical inflammatory response in the lungs and on a systemic level ("low-grade systemic inflammation") are considered to be key mechanisms. They promote secondary alterations in the body, such as vascular or metabolic processes, and may also result in the currently studied epigenetic phenomena or neuroinflammation. In this context, the health significance of soluble particulate matter and the role of ultrafine particles translocated across biological membranes into blood vessel and transported via the circulation to secondary target organs, such as liver, brain or the fetus, are intensively discussed.Diabetes is one of the leading chronic diseases worldwide, with a prevalence of almost 14 % in Germany. Although lifestyle factors are the main causes, current evidence suggests that long-term exposure to air pollution may additionally increase the risk for type 2 diabetes. Supporting evidence for a causal role of air pollution is provided by studies addressing the regulation of the blood glucose levels in metabolically healthy participants, insulin sensitivity, or pregnancy-related diabetes. Experimental studies provide further support for plausible biological mechanisms. However, prospective studies are needed to gain more evidence, taking multiple lifestyle and environmental factors, such as green space and noise, and an improved individual exposure assessment into account.The aging population has an increased risk of neurodegenerative diseases. First studies point towards a contribution of chronic exposure to air pollution, specifically by particulate matter. Several studies report its association with decreased neurocognitive capacity or an increased prevalence of dementia or Alzheimer's disease in adults. However, the studies are inhomogeneous regarding design, exposure and outcome, leading to inconsistent results. With respect to the influence on neurocognitive development of children, first studies suggest an association between the level of air pollution, e. g. at school, and delayed cognitive development.Even though the evidence for the different biological endpoints during pregnancy is still heterogeneous, the studies generally point towards an adverse impact of air pollution on the maternal and fetal organisms. The strongest evidence exists for low birth weight, with small effect sizes of only some grams, and for a higher incidence of reduced birth weight (< 2500 g). An increased risk for gestational hypertension and preeclampsia underscores the possible impact of exposure to air pollution on the maternal organism. However, the current body of evidence does not yet allow a final conclusion on the influence of intrauterine exposure to air pollution regarding early childhood lung function and development of allergies, particularly in light of the fact that it is hard to distinguish in epidemiological studies between the effects of pre- and postnatal exposure.

[Breathing: Ambient Air Pollution and Health - Part II]. / Atmen: Luftschadstoffe und Gesundheit ­ Teil II.

The second part of the DGP-statement on adverse health effects of ambient air pollution provides an overview of the current ambient air quality in Germany and its development in the past 20 years. Further, effects of air pollution on the cardiovascular system und underlying pathophysiological mechanisms are introduced. Air pollutants form a highly complex and dynamic system of thousands of organic and inorganic components from natural and anthropogenic sources. The pollutants are produced locally or introduced by long-range transport over hundreds of kilometers and are additionally subjected to local meteorological conditions. According to air quality regulations ambient air quality is monitored under uniform standards including immission of particulate matter, up to 2.5 µm (PM2.5) or 10 µm (PM10) in aerodynamic diameter, and of nitrogen dioxide (NO2) or ozone (O3). The clean air measures of recent years led to a continuous decline of air pollution in the past 20 years in Germany. Accordingly, the focus is nowadays directed at population-related health hazards caused by low concentrations of air pollution. Exceeded limits for sulfur dioxide, carbon monoxide, benzene and lead are not detected anymore. Also the number of days with increased ozone concentration declined, although the annual mean concentration is unaltered. Decreasing concentrations of particulate matter and NO2 have been observed, however, about 40 % of the monitoring stations at urban traffic sites still measure values exceeding current limits for NO2. Moreover, the stricter, solely health-based WHO-standards for PM2.5, PM10 and NO2 are still not met so that an optimal protection from air pollution-related health hazards is currently not given for the German population. In recent years, the findings of numerous cross-sectional and longitudinal studies underscored adverse effects of air pollution on the cardiovascular system, especially for particulate matter, although the level of evidence still varies for the different health outcomes. Further, the studies show that cardiovascular health hazards on the population level are of higher relevance than those for the respiratory system. The existing evidence for cardiovascular mortality, hospitalization, ischemic heart diseases, myocardial infarction and stroke can be regarded as strong, while that for heart failure is rather moderate. While the evidence for air pollution-related short-term alteration of the cardiac autonomic balance can be considered as sufficient, long-term effects are still unclear. Likewise, the heterogeneous findings on air pollution-related arrhythmia do currently not allow a distinct conclusion in this regard. A large number of studies support the observation that both, short- and long-term air pollution exposure contribute to increased blood pressure, may impair vascular homeostasis, induce endothelial dysfunction and promote the progression of atherosclerotic lesions. These effects provide reasonable biological explanation for the fatal events associated with exposure to air pollution. Short-term exposure may not pose a significant risk on healthy individuals but may be considered as precursor for fatal events in susceptible populations, while repetitive or long-term exposure may contribute to the development of cardiovascular diseases even in healthy subjects.

[Telemonitoring in heart failure : Update on health-related and economic implications]. / Telemonitoring bei Herzinsuffizienz : Update zu gesundheitlichen und ökonomischen Implikationen.

BACKGROUND: Heart failure is one of the most common and cost-intensive chronic diseases worldwide. Telemonitoring offers the potential to improve care of heart failure treatment and reduce cost. Empirical findings of its efficacy are inconsistent up to now. This systematic review examines the current state of research regarding health-related and economic endpoints. METHODS: A systematic review was conducted in July 2016 using the PubMed database and randomised controlled trials for the years 2011-2016. Only clinical research trials with heart failure patients were considered where the intervention was performed using external monitoring devices which transmitted data via information and communication technology. In all, 10 clinical trials were included. RESULTS: There is no definite evidence regarding improvement in care based solely on the most recent literature. Hospitalisation for heart failure and health-related quality of life were most positively influenced. There was no correlation between mortality and hospitalisations for all causes regarding telemonitoring. The overall costs tended to be higher for telemonitoring. CONCLUSION: Further research is needed to examine the health-related and economic benefits of telemonitoring for heart failure. A particular challenge is the evidence of cause-effect relationships within complex technology-supported health-care settings. The latest studies support the previous state of research.

[The Role of Psychological and Technology-related Personality Traits and Knowledge Levels as Factors Influencing Adoption of Telemonitoring by Medical Professionals]. / Die Rolle psychologischer und technikbezogener Persönlichkeitsmerkmale sowie individueller Wissensbestände von Ärztinnen und Ärzten für die Adoption des Telemonitorings in der medizinischen Versorgung.

OBJECTIVES: Information and communication technologies are becoming increasingly important in health care. Randomized clinical trials have shown that telemonitoring in particular leads to improved quality of care as well as shortened hospital stays and reduced health care costs. For its long-term anchoring in medical care, user-oriented technology needs to be developed, taking into account the complex structures of technology acceptance METHODS:: Knowledge of and attitudes towards telemonitoring amongst medical professionals were investigated using an online-based approach with a random sample of n=614; the response rate was 21% (n=133). The emergence of positive attitude patterns towards telemonitoring was analyzed using the relationships between psychological and technology-related personality traits, and perceived knowledge was determined using a regression model. RESULTS: Positive attitudes towards telemonitoring are significantly influenced by the individual's knowledge and agreeableness, which is strongly characterized by altruistic traits and interpersonal trust. There is a strong association with an improvement in the quality of care, while there are differences in attitudes towards telemonitoring between health care sectors and gender. Overall, only 57% of the physicians surveyed feel sufficiently informed about the use of telemonitoring. CONCLUSION: Medical evidence is crucial for the further development of telemedicine in general and telemonitoring in particular. Improvements need to be made in knowledge transfer, the exchange of best practice solutions and the anchoring of telemedicine in education and training.

[Significance of microbial colonisation in materials for orthopaedic technology. New insights]. / Bedeutung der mikrobiellen Besiedlung orthopädietechnischer Materialien. Neue Erkenntnisse.

A great problem in the treatment of diabetes are infections of diabetic feet. A likely reservoir of microorganisms are contaminated orthopaedic materials. Insoles from 70 patients were examined for potential microbial colonisation. Commonly employed materials were contaminated in vitro under standardised conditions using known microorganisms. After treating with an alcoholic skin disinfectant, the organisms were counted semiquantitatively. In addition to pathogens, the surfaces showed mainly microorganisms present in the normal skin flora. In all materials tested, disinfection reduced the number of organisms by 4-5 log orders. It could be shown that simple disinfection (wiping) reduces the microorganisms present on orthopaedic materials to an acceptable number. Further studies are needed to determine whether this also reduces the incidence of diabetic skin and soft tissue infection.

[The importance of MRSA in patient care. Epidemiology, prevention and therapy]. / Bedeutung von MRSA in der Patientenversorgung. Epidemiologie, Prophylaxe und Therapie.

Methicillin-resistant Staphylococcus aureus (MRSA) has for several years been increasingly spreading at inpatient and outpatient health care facilities. This constitutes a great epidemiological problem. Measures are needed for MRSA management, including screening, hygiene, containment, and sanitation as well as for a stricter control of antibiotic use. In order to be able to monitor and assess the MRSA problem in the future, there are surveillance systems which can provide approaches for continuously improving MRSA management and thus offer a long-term solution. In this context, regional networks for implementing MRSA prevention strategies are of particular importance. Their goal is reducing MRSA-caused infections in an area and stop circulation of MRSA between the various health care facilities. For the management of MRSA infections, interdisciplinary cooperation between the attending orthopedic specialist and the clinical microbiologist is very important for planning an effective treatment regimen to ensure a successful outcome, particularly in view of the growing shortage of resources in the healthcare system.

[Environment-related health disorders. Experience and perspectives in the care of patients with environment-related health disorders]. / Umweltbezogene Gesundheitsstörungen. Erfahrungen und Perspektiven umweltmedizinischer Patientenversorgung.

Environmental medicine outpatient clinics, counseling centers, and practicing physicians have observed environment-related health disorders in patient groups of mixed age as well as for groups consisting only of adults or children. Practicing physicians suspected correlations between environmental factors and health disorders in 36-45% of cases, environmental medicine outpatient clinics and counseling centers in 4-34% for mixed-age groups, 0-24% for adults, and 9-13% for children. A comparison of these data is difficult due to differences in data acquisition, evaluation methods, and descriptive statistics used. Furthermore, data on children are insufficient. Patient-oriented environmental medicine faces a number of problems regarding determination of exposure, effects, and susceptibility, including a lack of scientifically verified cause-and-effect models as well as incorrect diagnoses, attributions, and conclusions. In view of the scope and intensity of environment-related health disorders, the topic cannot be ignored. A functioning program of environmental medicine counseling and patient care is needed for practicing physicians, universities and/or the public sector to deliver effective primary medical care in this field. As always, the building blocks of environ-mental medicine counseling are medical history, physical examination, differential diagnosis, human biomonitoring, and on-site inspection with environmental monitoring while also taking gender differences into account. Uniform basic documentation procedures and health science analyses will help to optimize patient care in environ-mental medicine. The value of a diagnostic algorithm in the care of patients with environment-related health disorders is beyond dispute. Last but not least, quality assurance and control are a sine qua non of patient-oriented environmental medicine.

Are syndromes in environmental medicine variants of somatoform disorders?

To date, relatively little is known about the etiology, pathophysiology, diagnosis, therapy, prevention and prognosis of environment-related syndromes like multiple chemical sensitivity (MCS), idiopathic environmental intolerance (IEI), sick building syndrome (SBS), chronic fatigue syndrome (CFS), candida syndrome (CS) and burnout syndrome (BS). Part of the reason is that these syndromes have not been clearly defined and classified in scientific categories distinct from each other, and that they show clinical similarities to classified somatoform disorders. Furthermore, there are at least three possible explanations for the existence of these syndromes: (1) The syndromes may result from the interaction of environmental factors, individual susceptibility and psychological factors (i.e., how they are perceived and seen by the patient); (2) they may reflect socially and culturally accepted methods of expressing distress; and/or (3) they may be iatrogenic. Despite all the uncertainties in evaluation of environmental syndromes, physicians have the duty to take the affected person's problems seriously. A comprehensive systematic classification which better accounts for these complex clinical manifestations is long overdue. Until these syndromes are well defined, the terms used for them should definitely not be applied to connote a specific disease process.

[The MRSA patient in technical orthopaedics and rehabilitation]. / Das Problem der MRSA-Infektionen bei der Behandlung des Diabetischen Fusssyndroms. Teil 1: Charakterisierung eines Patientenkollektivs.

Colonisation and infection of humans by methicillin-resistant Staphylococcus aureus (MRSA) was examined retrospectively at the Clinic of Technical Orthopedics and Rehabilitation of the University Clinic at Münster (Germany). The cohort consisted of 28 patients who over the period were microbiologically shown to harbour MRSA from January 1997 to June 2000. Out of these, only 16 patients were colonised and only 12 patients developed MRSA infection. The inpatient stay was longer for MRSA subjects than for non-MRSA subjects. All patients had chronic wound healing disorders of the lower extremities which were due to peripheral neuropathies, diabetes mellitus and/or obstructive disease of the arteries. All patients were at risk for colonisation with MRSA.

[The MRSA patient in technical orthopaedics and rehabilitation. Part 2: Hygiene management]. / Das Problem der MRSA-Infektionen bei der Behandlung des Diabetischen Fusssyndroms. Teil 2: Hygienemanagement.

One of the multiresistant pathogens is methicillin-resistant Staphylococcus aureus (MRSA),which was increasingly found in the 1980's. In the USA, the ratio of MRSA rose from 2% in 1975 to 29% in 1991. A similarly steep rise was seen in Germany, with the Paul Ehrlich Society for Chemotherapy reporting a rise from 1.7% in 1990 to 15.7% in 1998. In order to control MRSA, the Clinic and Polyclinic of Technical Orthopaedics and Rehabilitation at the University Clinic Münster, Germany,has set up a comprehensive hygiene management programme for early detection and treatment of nosocomial infections. In addition to addressing the usual problems of MRSA carriers (e.g., higher mortality, longer hospital stays, stigmatisation), these preventive measures are also aimed at combating MRSA-caused cost increases.

[Syndromes in environmental medicine: variants of somatoform disorders]. / Syndrome in der Umweltmedizin: Varianten von Somatisierungsstörungen?

Concerning the syndromes in environmental medicine, like Multiple Chemical Sensitivities (MCS), Idiopathic Environmental Intolerances (IEI), Sick Building Syndrome (SBS), Chronic Fatigue Syndrome (CFS), Candida Syndrome (CS), and Burnout Syndrome (BS), scientific knowledge in etiology, pathology, pathophysiology, diagnosis, therapy, prevention and prognosis is still lacking until now. A critical comparison shows that it is still impossible to find a scientifically satisfying delimitation. Syndromes in environmental medicine show clinical similarities to somatoform disorders. Furthermore, there are the following possible explanations for the existence of these syndromes: Firstly, they may be a complex interaction of environmental impacts, individual predispositions, psychological influences, as well as processes of mental perception and interpretation. Secondly, they may be an effect of distress influenced by culture and social structures and/or thirdly, they may be an latrogenic determination. A more comprehensive characterisation which better considers the complex clinical manifestations is overdue. Although there are neither scientifically validated procedures for diagnosis or therapy nor prophylactic measures, a hardly comprehensible number of partly unvalidated methods is in practical use. Until the syndromes are not finally defined the terms for the syndromes should not be applied to a certain disease. Despite all uncertainities in the evaluation of syndromes in environmental medicine, physicians have the duty to take the affected persons' problems seriously.

[Methicillin-resistant Staphylococcus aureus (MRSA). Current status and significance of preventing infection in technical orthopedics]. / Methicillin-resistenter Staphylococcus aureus (MRSA). Aktuelle Situation und Bedeutung der Infektionsprävention in der Technischen Orthopädie.

Many patients of the Clinic for Technical Orthopedics and Rehabilitation of the Munster University are facing several risk factors at the same time, which have to be considered for infection registration and therapy accordingly. The interaction of the known late consequences of diabetes mellitus creates the prerequisites which give way for infections of the soft parts and bones. Very often, patients are only being transferred to special university clinics after long-lasting pre-treatments as day-patients or inpatients. The integrity of patients physiological barriers is often broken through by the already existing morphological damages, and the function of the immune systems defence possibly is affected by already existing basic diseases. Parallel to the increasing importance of Staphylococcus aureus (S. aureus) being the pathogen for nosocomial infections, the resistance situation towards a lot of antibiotics has significantly and increasingly deteriorated. The methicillin resistance of S. aureus, i.e. the resistance of the pathogen towards so-called staphylococcus-effective penicillinase-resistant penicillins (isoxazolylpenicillins), is presently creating the especially for the clinical practice problematic resistance mechanisms. The methicillin (oxacillin)-resistant S. aureus (MRSA, ORSA) stems usually present the phenomenon of multiresistance, i.e. the resistance towards substances of several classes of antibiotics, and, therefore, are not only resistant to all beta-lactamantibiotics (penicillins, cephalosporins, carbapenems). Thus, MRSA infections become a significant risk factor for the respective patients. In many cases there are only a very few options left for an antibiotic therapy. The increasing and often unquestioned use of "reserve substances" is leading to a selection of pathogens creating resistances to the corresponding substances. This results in a resistance spiral which makes an antibiotic therapy more and more difficult.

Induction of sister chromatid exchanges (SCE) in human tracheal epithelial cells by the fractions PM-10 and PM-2.5 of airborne particulates.

Recent epidemiological studies in the United States and in Europe indicate, that the coarse fraction (PM-10) of airborne particulates, smaller than 10 microm and particularly the fine fraction (PM-2.5) smaller than 2.5 microm are responsible for adverse health effects, causing an increasing morbidity and mortality. Furthermore, an association was reported between air pollution, especially the levels of the fine respirable particles and death from lung cancer. The epithelium of the respiratory tract is the major target of airborne particulates and the location of the most common cancer in man, bronchogenic carcinoma. The genotoxic activity of the coarse (PM-10) and the fine fraction (PM-2.5) of airborne particulates leading to mutation and cancer can be analyzed using in vitro models of human bronchoepithelial cells. In our study collection of the coarse (PM-10) and the fine fraction (PM-2.5) of airborne particulates was conducted in the winter of 1996 in the highly industrialized Rhine-Ruhr region (Germany). For collection we selected an urban area (Düsseldorf), an industrialized area Duisburg and a rural area (Borken). Airborne particulates were collected with a Low Volume M-10 dichotomous sampler (Graseby-Andersen) equipped with glass fiber filters. Chemical substances were extracted from filters with di-chloromethane and quantitatively transferred to dimethylsulfoxide (DMSO). As target cells for testing the genotoxic activity we used cultures of the human bronchioepithelial cell line (BEAS-2B). As a sensitive cytogenetic endpoint for evaluation of the genotoxic activity of extracts of airborne particulates we utilized the induction of 'sister chromatid exchanges' (SCE). The coarse fraction PM-10 and especially the fine fraction PM-2.5 of airborne particulates from all three locations caused a strong dose-related induction of 'sister chromatid exchanges'. The fine fractions PM-2.5 from the three locations exerted a stronger genotoxic activity than the corresponding coarse fractions PM-10. While airborne particulates from Düsseldorf and Duisburg revealed a comparable genotoxic activity, the samples from Borken disclosed a lower genotoxicity. It is important that especially the fine fraction PM-2.5, exerted a strong genotoxicity equivalent to substances of airborne particulates from less than 0.5 m3 of air. Results of this study and earlier reports demonstrate that the human tracheobronchial epithelial cell line (BEAS-2B) in vitro offer a reliable and sensitive in vitro model for genotoxicity testing of airborne particulates, especially of the coarse (PM-10) and fine fraction (PM-2.5).

Malignant transformation of Syrian hamster kidney cells in vitro by interaction of airborne particulates and simian virus (SV-) 40.

Permanent inhalation of great variety of air pollutants raises serious problems concerning adverse effects on human health. Especially in airborne particulates more than 1000 inorganic and organic compounds have been detected, among them also carcinogens and mutagens, such as polycyclic aromatic hydrocarbons, polycyclic-aza-compounds, carbonic acids, phenols, ketons, heavy metals, etc. The role of airborne particulates in genesis of the most common cancer in man, the bronchogenic carcinoma, is still unresolved. Samples of airborne particulates were collected at locations of the highly industrialized Rhine-Ruhr region (Germany) employing a high volume sampler HVS-150 (Ströhlein Instruments) prepared with glass fibre filters. Samples were extracted in a Soxhlet-apparatus with dichloromethane. Using a rotating evaporator the solvent was evaporated and the residual substances dissolved in dimethylsulfoxide for cell culture experiments. Carcinogenic activity of extracts of airborne particulates was evaluated by the bioassay of 'enhancement' of malignant cell transformation in vitro. In this bioassay, exponentially growing cell cultures from kidneys of the Syrian golden hamster were treated with various concentrations of extracts of airborne particulates for 18 h. Thereafter, exposed and control cultures were infected with the papovavirus simian virus (SV-) 40 (Strain RH 911) at a multiplicity of infection (M.O.I.) of 300-500 ID50. A strong dose-dependent 'enhancement' of cell transformation frequency occurred in kidney cultures of the Syrian golden hamster pretreated with extracts of airborne particulates and thereafter infected with the simian virus 40. It has to be emphasized, that very low quantities of extractable substances corresponding to particulates collected from 0.5 m3 of air, induced a strong highly significant increase in cell transformation frequency. Inoculation of transformed cells into syngeneic animals produced in a high percentage malignant tumors, mostly sarcomas.

Comparative analysis of cyto- and genotoxic effects of airborne particulates on human and rodent respiratory cells in vitro.

In our highly industrialized world air pollution has become an important topic. Beside gaseous pollutants airborne particulates are of great medical concern, containing several hundred mostly organic substances. They are incriminated to cause an excess mortality. Airborne particulates were collected in the heavily industrialized Ruhr region utilizing a high volume sampler HVS 150 (Ströhlein Instruments) equipped with glass fibre fiiters. Chemical substances were extracted with dichloromethane and quantitatively transferred to dimethyl sulfoxide for tissue culture experiments. Cytotoxicity of extracts was determined by reduction of 'plating efficiency' of human cell line A-549 (pneumocyte type II). The induction of 'sister chromatid exchanges' was used as a sensitive bioassay for detection of genotoxic activity of airborne particulates. As target cells we utilized tracheal epithelial cells of the Syrian golden hamster and the rat, human bronchial epithelial cells of line BEAS-2B and human lymphocytes. Quantities of substances equivalent to airborne particulates from 4 and more m(3) air exerted cytotoxic effects, while quantities of substances from 0.5 m(3) of air were markedly genotoxic.

Sister chromatid exchanges in rodent tracheal epithelium exposed in vitro to environmental pollutants.

In our highly industrialized world, air pollution has become a major topic. The human respiratory tract is constantly exposed to air pollutants by inhalation. Besides gaseous pollutants airborne particulates are of great importance, containing a complex mixture of several hundred substances. The tracheobronchial epithelium is the major target site of airborne particulates as well as the origin of the most common cancer in man, the bronchogenic carcinoma. In our study we collected samples of airborne particulates in winter 1991 in the highly industrialized Rhine-Ruhr area (Germany) with a high-volume sampler on glass fiber filters. Airborne particulates were extracted with di-chloromethane and quantitatively transferred to dimethyl sulfoxide (DMSO) for tissue culture experiments. As target cells for genotoxicity testing we used cultures of rodent tracheal epithelial cells from the Syrian golden hamster and from the rat. Induction of "sister chromatid exchanges" (SCE) was utilized as a sensitive cytogenetic endpoint for evaluation of the genotoxic activity of extracts of airborne particulates. In presence of global extracts (GEX) we observed a dose-dependent, highly significant increase of SCE in tracheal epithelial cells of the Syrian golden hamster and of the rat. It is remarkable that even quantities of chemical substances equivalent to airborne particulates from less than 1 m3 of air were genotoxic. Results of this study and earlier reports demonstrate that rodent tracheal epithelial cells offer a reliable and sensitive in vitro model for genotoxicity testing of airborne particulates. Therefore, tracheal epithelial cells in vitro appear a meaningful alternative to other human and rodent cell culture systems which have been used for genotoxicity testing of air pollutants.

Rodent tracheal epithelial cells in vitro: a comparative study of normal cells, enhanced growth variants, SV-40 transformed cells and their interactions.

Tracheal epithelial cells of the golden Syrian hamster can be successfully cultivated in vitro and applied as a model system of respiratory tract epithelium. By morphology and growth characteristics of tracheal epithelial cells, "normal cells", "enhanced growth variants" and "transformed cells" were distinguished in vitro. Hamster tracheal epithelial cells, transformed by Simian virus (SV)-40 expressed in cell nuclei the specific tumor (T-) antigen and showed an accumulation of tumor suppressor protein p53 by immunofluorescence. Cocultivation of "enhanced growth variants" and of "transformed cells" on a "feeder layer" of normal hamster tracheal epithelial cells revealed remarkable differences in loss of "contact inhibition of growth". A "cytokine" released by NIH-3T3 cells stimulated cell proliferation and seems to be important for cell growth of hamster tracheal epithelial cells. Preliminary characterization of the "cytokine" disclosed a molecular weight of more than 30 kDa, a relative thermostability and a loss of activity by treatment with mercaptoethanol indicating disulfide bridges in a molecule.