Biomedical subjects

C Schindler

Publications and source records attributed to C Schindler.

At least 19 recordsLinked to original sources

PubMed2001

Respiratory symptoms in Swiss farmers: an epidemiological study of risk factors.

BACKGROUND: The study was undertaken to assess the prevalence and risk factors of self-reported asthma, symptoms of chronic bronchitis, hay fever, and work-related respiratory symptoms in Swiss farmers as well as to compare the prevalence rates of respiratory symptoms with the Swiss population (SAPALDIA-Study). METHODS: An epidemiological study was performed with a representative sample of 1,542 Swiss farmers using a self-administered questionnaire. To investigate the effect of the type of farming on reported symptoms, the farmers were subdivided into seven groups according to the time farmers spent in different animal confinement buildings. A multivariate analysis was performed by the methods of binary and multivariate logistic regression adjusted for age and smoking habits. RESULTS: In farmers the prevalence rate was 16.0% for chronic bronchitis, 15.4% for asthma symptoms, and 42.0% for reporting at least one work-related symptom. Using logistic regression analysis, it was established that poultry farming and pig/cattle farming was a risk factor for reporting nasal irritation at work [OR 5.33, (1.57-18.0), OR 3.37 (1.04-10.87)]. Poultry farmers experienced the highest symptom rates. In crop farmers, the prevalence for chronic bronchitis was increased [OR 2.32 (1.03-5.23)]. Over 4 hr spent per day in animal confinement buildings more than doubled the risk for reporting chronic bronchitis [OR 2.61 (1.01-6.76)] and phlegm [OR 2.3 (0.99-5.4)] independent of the type of farming. The comparison of Swiss farmers with the Swiss population showed a twofold elevated risk of reporting chronic bronchitis [OR 1.89 (1.32-2.95)] and a 4.5-fold elevated risk for bringing up phlegm regularly [OR 4.5 (3.25-6.69)] in farmers. In contrast, the risk of farmers to report nasal allergies was less than half as high [OR 0.40 (0.29-0.56)] as that of the general population. CONCLUSIONS: This study shows that agricultural work in Switzerland is associated with an elevated risk for reporting symptoms of chronic bronchitis and chronic phlegm compared with the general Swiss population. These main results most likely indicate occupational disorders as the exposure-response relationship (hours spent in animal confinements) was particularly obvious for these symptoms.

Adolescent↗

PubMed2001

Low incidence of SV40-like sequences in ependymal tumours.

Between 1955 and 1963, millions of children and adults were exposed to SV40-contaminated poliovirus vaccines. The oncogenic potential of this polyomavirus was revealed when intracerebral inoculation of SV40 into newborn hamsters resulted in the development of ependymomas and choroid plexus papillomas. Subsequently, SV40-like sequences were repeatedly detected in human ependymomas with broadly ranging incidence rates of 7-90%. Most epidemiological studies, however, have not described an increased occurrence of ependymomas. To gain more data on this controversial issue, this study examined 62 archived ependymal tumours from 31 children and 31 adults who underwent surgery between 1990 and 1999. Only three (5%) of the tumours--including 24 classical, 20 anaplastic, and 12 myxopapillary ependymomas; one subependymoma; and five ependymoblastomas--revealed subgenomic SV40 sequences. None of the ependymomas in patients born between 1920 and 1960 demonstrated SV40-like sequences. The positive tumours represent 7% of grade II and III ependymomas (two paediatric and one adult tumour). DNA sequencing of the PCR product revealed identical sequences of SV40 in the positive ependymal tumours. Compared with the results from other countries, this incidence rate is relatively low. Therefore, it seems likely that significant differences between individual countries exist regarding the prevalence of SV40-positive ependymomas. These differences may reflect different degrees of exposure to SV40-contaminated polio vaccine.

Adolescent↗

PubMed2001

Influence of selenium supplements on the post-traumatic alterations of the thyroid axis: a placebo-controlled trial.

OBJECTIVE: To investigate whether early selenium (Se) supplementation can modify the post-traumatic alterations of thyroid hormone metabolism, since the first week after trauma is characterised by low plasma Se and negative Se balances. DESIGN: Prospective, placebo-controlled randomised supplementation trial. SETTING: Surgical ICU in a tertiary university hospital. PATIENTS: Thirty-one critically ill trauma patients aged 42 +/- 16 years (mean +/- SD), with severe multiple injury (Injury Severity Score 30 +/- 7). INTERVENTION: Supplementation during the first 5 days after injury with either Se or placebo. The selenium group was further randomised to receive daily 500 microg Se, with or without 150 mg alpha-tocopherol (AT) and 13 mg zinc supplements. The placebo group received the vehicle. Circulating Se, AT, zinc, and thyroid hormones were determined on D0 (= day 0, admission), D1, D2, D5, D10, and D20. RESULTS: Plasma Se, low on D0, normalised from D1 in the selenium group; total T4 and T3 increased more and faster after D2 (P = 0.04 and 0.08), reverse T3 rising less between D0 and D2 (P = 0.05). CONCLUSIONS: Selenium supplements increased the circulating Se levels. Supplementation was associated with modest changes in thyroid hormones, with an earlier normalisation of T4 and reverse T3 plasma levels. The addition of AT and zinc did not produce any additional change.

Adult↗

PubMed2001

Comparison of the heparin coated vs the uncoated Jostent--no influence on restenosis or clinical outcome.

AIMS: Heparin coating of stents is thought to reduce stent thrombosis and restenosis rates. However, clinical data comparing coated and uncoated stents of the same model are lacking. We compared the heparin coated (C) and the uncoated (U) version of the Jostent stent with regard to the clinical and angiographic outcome after 6 months. METHODS AND RESULTS: Provisional stenting was done in 277 patients and 306 lesions; only 40 were Benestent-II like lesions. Delivery success rate was 98.4%. Both groups (C/U: n=156/150 lesions) were comparable in clinical and procedural data. Post stenting, reference diameter (C/U: 2.68+/-0.56/2.66+/-0.53 mm) and minimal lumen diameter did not differ (C/U: 2.48+/-0.47/2.48+/-0.52 mm). During follow-up the rate of subacute stent thrombosis (C/U: 1.9%/1.3%) and myocardial infarction did not differ. Angiography at the 6-month follow-up (79.4%) revealed no difference in restenosis rate (C/U: 33.1%/30.3%). Risk factors for restenosis were a type B2/C lesion (P<0.02), a stented segment longer than 16 mm (P<0.006) and a stent inflation pressure <14 bar (P<0.0063). CONCLUSION: Corline heparin coating of the Jostent has no impact on the in-hospital complication rate, stent thrombosis or restenosis. The Jostent design gives a high procedural success rate and satisfying result at 6 months in an everyday patient population undergoing provisional stenting.

Anticoagulants↗

PubMed2001

Visual and motor evoked potentials in the course of multiple sclerosis.

While evoked potentials are sensitive tools for diagnosing multiple sclerosis, little is known about their prognostic value and their role in determining the course of the disease. To validate the visual and motor evoked potentials (VEP and MEP) as measures for the course of multiple sclerosis, we examined prospectively 30 patients with relapsing-remitting or secondary progressive multiple sclerosis. The Expanded Disability Status Scale (EDSS), VEP and MEP were measured at entry and after 6, 12 and 24 months. The Spearman rank correlation was used for statistical analysis. Applying multiple regression in 15 randomized patients allowed derivation of a formula for predicting changes in EDSS score based on changes in MEP and VEP. Validation was done by comparing the predicted with the real changes in EDSS in the other 15 patients. The number of pathological VEP and MEP results correlated at all four measurement points with the EDSS (rho > or = 0.6, P < or = 0.01). When the latencies of VEP and MEP were combined using the sum of their Z scores, correlation with the EDSS was even more significant (rho > or = 0.6, P < 0.001). Changes over time of electrophysiological data and EDSS were also correlated (rho = 0.43, P < 0.05). Moreover, VEP and MEP at baseline correlated with the EDSS after 2 years (rho = 0.43,P = 0.03). Reliable prediction of the course of multiple sclerosis for individual patients is not possible from VEP and MEP data. However, we conclude that, for groups of patients with secondary progressive or relapsing-remitting multiple sclerosis the combined testing of VEP and MEP yields numerical data that allow objective estimation of the course and prognosis of the disease.

Adult↗

PubMed2001

Low-potassium and glucose-free dialysis maintains urea but enhances potassium removal.

BACKGROUND: The influence of potassium (K) removal on dialysis efficiency as measured by urea elimination is not clear. In this prospective, randomized, cross-over study we investigated the magnitude of K removal and its effect on urea (u) elimination during high-flux haemodialysis (HD). METHODS: Twelve stable, non-diabetic HD patients were investigated during three one-week standardized HD periods (1.8 m(2) high-flux polysulphone dialyser, treatment time 240 min, Qb = 300 ml/min, Qd = 500 ml/min, dialysate without glucose, bicarbonate 40 mmol/l), using dialysates containing 0 (0K), 1 (1K), and 2 (2K) mmol/l of K. Mass removal of K (M(K)) and u (M(U)) were measured during the mid-week treatment by partial dialysate collection. Urea reduction rate (URR) and Kt/V were determined. RESULTS: 0K, 1K and 2K treatments were perfectly comparable. Plasma K (PK) continuously declined reaching stable concentrations after 180 min. While 0K dialysate removed 117.1 mmol, 80.2 and 63.3 mmol (P < 0.001) were removed by 1K and 2K baths respectively. M(U) was not influenced by M(K) (r = 0.22) and amounted to 491.1 (0K), 508.6 (1K), and 506.2 (2K) mmol (NS) respectively. Accordingly, urea clearance, URR and Kt/V were constant during 0K, 1K and 2K treatments. CONCLUSIONS: Potassium-free dialysate significantly enhances potassium elimination. Potassium removal has no influence on urea elimination. High potassium removal, when needed, does not impair dialysis efficiency as measured by urea kinetics in high-flux, glucose-free, 40 mmol/l bicarbonate HD.

Adult↗

PubMed2001

Confounding and effect modification in the short-term effects of ambient particles on total mortality: results from 29 European cities within the APHEA2 project.

We present the results of the Air Pollution and Health: A European Approach 2 (APHEA2) project on short-term effects of ambient particles on mortality with emphasis on effect modification. We used daily measurements for particulate matter less than 10 microm in aerodynamic diameter (PM10) and/or black smoke from 29 European cities. We considered confounding from other pollutants as well as meteorologic and chronologic variables. We investigated several variables describing the cities' pollution, climate, population, and geography as potential effect modifiers. For the individual city analysis, generalized additive models extending Poisson regression, using a smoother to control for seasonal patterns, were applied. To provide quantitative summaries of the results and explain remaining heterogeneity, we applied second-stage regression models. The estimated increase in the daily number of deaths for all ages for a 10 microg/m3 increase in daily PM10 or black smoke concentrations was 0.6% [95% confidence interval (CI) = 0.4-0.8%], whereas for the elderly it was slightly higher. We found important effect modification for several of the variables studied. Thus, in a city with low average NO2, the estimated increase in daily mortality for an increase of 10 microg/m3 in PM10 was 0.19 (95% CI = 0.00-0.41), whereas in a city with high average NO2 it was 0.80% (95% CI = 0.67-0.93%); in a relatively cold climate the corresponding effect was 0.29% (95% CI = 0.16-0.42), whereas in a warm climate it was 0.82% (95% CI = 0.69-0.96); in a city with low standardized mortality rate it was 0.80% (95% CI = 0.65-0.95%), and in one with a high rate it was 0.43% (95% CI = 0.24-0.62). Our results confirm those previously reported on the effects of ambient particles on mortality. Furthermore, they show that the heterogeneity found in the effect parameters among cities reflects real effect modification, which is explained by specific city characteristics.

Aged↗

PubMed2001

Perceived environmental housing quality and wellbeing of movers.

STUDY OBJECTIVE: To examine whether changes in environmental housing quality influence the wellbeing of movers taking into account other dimensions of housing quality and sociodemographic factors. DESIGN: Cross sectional telephone survey. Associations between changes in satisfaction with 40 housing quality indicators (including environmental quality) and an improvement in self rated health (based on a standardised question) were analysed by multiple logistic regression adjusting for sociodemographic variables. Objective measures of wellbeing or environmental quality were not available. SETTING: North western region of Switzerland including the city of Basel. PARTICIPANTS: Random sample of 3870 subjects aged 18-70 who had moved in 1997, participation rate 55.7%. RESULTS: A gain in self rated health was most strongly predicted by an improved satisfaction with indicators related to the environmental housing quality measured as "location of building" (adjusted odds ratio (OR) =1.58, 95% confidence intervals (CI) =1.28, 1.96) and "perceived air quality" (OR=1.58, 95% CI=1.24, 2.01) and to the apartment itself, namely "suitability" (OR=1.77, 95% CI=1.41, 2.23), "relationship with neighbours" (OR=1.46, 95% CI=1.19, 1.80) and "noise from neighbours" (OR=1.32, 95% CI=1.07, 1.64). The destination of moving and the main reason to move modified some of the associations with environmental indicators. CONCLUSION: An improvement in perceived environmental housing quality was conducive to an increase in wellbeing of movers when other dimensions of housing quality and potential confounders were taken into account.

Adolescent↗

PubMed2001

Short-term variation in air pollution and in average lung function among never-smokers. The Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA).

The present analysis was directed at investigating associations between short-term variations in air pollutant levels (NO2, total suspended particulates [TSP], O3) and cross-sectional lung function (FVC, FEV1, and forced expiratory flow at 25% to 75% of FVC [FEF25-75]) within a random sample of 3,912 adult never-smokers from eight areas of Switzerland (i.e., participants in the Swiss Study on Air Pollution and Lung Diseases in Adults [SAPALDIA] cross-sectional study, 1991). Within each local data set, the logarithms of FVC, FEV1, and FEF25-75 were regressed against the 24-h-means of NO2 and TSP and the 8-h mean of O3 (10:00 A.M. to 6:00 P.M.) on the examination day, with control for subjects' sex, age, height and weight, seasonal fluctuations and weekly cycles and meteorologic factors. On average, a 10-microg/m3 increment in the daily level of NO2, TSP, and O3 was associated with decrements in FEV1 of 0.67% (95% confidence interval [CI]: 0.13% to 1.21%), 0.46% (95% CI: 0.14% to 0.78%), and 0.51% (95% CI: 0.13% to 0.88%), respectively. Moreover, 10-microg/m3 increments in NO2 and TSP were associated with decrements in FVC of 0.73% (95% CI: 0.22% to 1.23%) and 0.36% (95% CI: 0.06% to 0.66%), respectively, and a 10-microg/m3 increment in O(3) was associated with a decrement in FEF25-75 of 1.04% (95% CI: 0.22% to 1.85%). Our results suggest that FVC, FEV1, and FEF25-75 vary with the daily level of NO2, TSP, and O3, but that these measures of lung function do not allow separation of the effects of particulates from those of NO2.

Adolescent↗

PubMed2001

Lymphocytes are important in early atherosclerosis.

Lymphocytes represent a potentially important proinflammatory cell that localizes to atherosclerotic lesions. To determine whether they contribute to lesion development, atherosclerosis-prone (LDLR(-/-)) mice were crossed with lymphocyte-deficient (RAG1(-/-)) mice to generate double knockout progeny. After 8 weeks on a Western-type diet (WTD), lesion development was reduced by 54% in double knockout mice, as compared with matched LDLR(-/-) controls. However, these significant differences in lesion area gradually subsided as the WTD was continued for 12 and 16 weeks. Consistent with this observation, histological studies determined that lesion initiation and early progression were delayed in RAG1/LDL-R double knockout mice. Differences in lesion area did not correlate with any significant alterations in plasma lipid levels. These studies suggest that lymphocytes play an important role early in atherogenesis.

Animals↗

PubMed2001

Clinical diagnosis of current asthma: predictive value of respiratory symptoms in the SAPALDIA study. Swiss Study on Air Pollution and Lung Diseases in Adults.

Bronchial asthma is a very common disease which often remains underdiagnosed. The aim of this study was to determine the predictive value of the most common respiratory symptoms and to explore the best symptom combinations to predict diagnosis of asthma. A questionnaire comprising common respiratory symptoms was submitted to 9,651 subjects aged 18-60 yrs, randomly selected from the Swiss population, of whom 225 subjects (2.3%) had current asthma as confirmed by their general practitioner. Based on these data the authors calculated the predictive values of single symptoms and symptom combinations to diagnose asthma. Wheezing was the most sensitive single symptom (sensitivity 75%). Simple symptoms such as wheezing with dyspnoea, chronic phlegm or chronic cough had specificity greater than 95%. Wheezing with dyspnoea (WD) or nocturnal dyspnoea (ND) had the best positive predictive value (PPV) as isolated symptoms (24% and 21%, respectively). When combining symptoms, wheezing associated with daily dyspnoea at rest or nocturnal dyspnoea showed the best PPV (42% and 39%, respectively), almost double single symptoms such as WD or ND. Wheezing associated with at least two of the three nocturnal symptoms (nocturnal dyspnoea, nocturnal cough or nocturnal chest tightness) had a sensitivity of 80% to diagnose asthma. In conclusion, respiratory symptoms obtained by medical history are reliable predictors of asthma. The findings suggest that particular combinations of symptoms are clinically useful in the differential diagnosis of asthma.

Adolescent↗

PubMed2000

A Stat3-interacting protein (StIP1) regulates cytokine signal transduction.

Genetic and biochemical studies have led to the identification of the Stat3-Interacting Protein StIP1. The preferential association of StIP1 with inactive (i.e., unphosphorylated) Stat3 suggests that it may contribute to the regulation of Stat3 activation. Consistent with this possibility, StIP1 also exhibits an affinity for members of the Janus kinase family. Overexpression of the Stat3-binding domain of StIP1 blocks Stat3 activation, nuclear translocation, and Stat3-dependent induction of a reporter gene. These studies indicate that StIP1 regulates the ligand-dependent activation of Stat3, potentially by serving as a scaffold protein that promotes the interaction between Janus kinases and their Stat3 substrate. The ability of StIP1 to associate with several additional members of the signal transducer and activator of transcription family suggests that StIP1 may serve a broader role in cytokine-signaling events.

3T3 Cells↗

PubMed2000

Myeloid differentiation of FdCP1 cells is dependent on Stat5 processing.

The IL-3 family of cytokines transduces signals through Stat5 and regulates myeloid development. Previous studies have determined that a carboxy terminally truncated isoform of Stat5 is activated in immature myeloid cells. This isoform, which lacks a transcriptional activation domain, is generated by a protein-processing event. To determine whether Stat5 cleavage plays an important role in the growth and maturation of myeloid progenitors, the FdCP1 model of myeloid maturation was evaluated. FdCP1 cells are IL-3-dependent myeloid progenitors that differentiate into monocytes when cultured in granulocyte macrophage-colony-stimulating factor (GM-CSF). Consistent with their immature phenotype, when FdCP1 cells are cultured in IL-3 they exhibit robust protease activity and signal through truncated Stat5 isoforms. In contrast, maturation leads to a loss of protease activity and a switch to the expression to full-length Stat5 isoforms. Introduction of a noncleavable, full-length Stat5 mutant into undifferentiated FdCP1 cells leads to a partially differentiated phenotype and prevents further differentiation in response to GM-CSF. These results support our hypothesis that Stat5 processing is important for myeloid maturation. (Blood. 2000;96:1358-1365)

Animals↗

PubMed2000

Percutaneous transluminal coronary angioplasty versus medical treatment for non-acute coronary heart disease: meta-analysis of randomised controlled trials.

OBJECTIVE: To determine whether percutaneous transluminal coronary angioplasty (angioplasty) is superior to medical treatment in non-acute coronary artery disease. DESIGN: Meta-analysis of randomised controlled trials. SETTING: Randomised controlled trials conducted worldwide and published between 1979 and 1998. PARTICIPANTS: 953 patients treated with angioplasty and 951 with medical treatment from six randomised controlled trials, three of which included patients with multivessel disease and pre-existing myocardial infarction. MAIN OUTCOME MEASURES: Angina, fatal and non-fatal myocardial infarction, death, repeated angioplasty, and coronary artery bypass grafting. RESULTS: In patients treated with angioplasty compared with medical treatment the risk ratios were 0. 70 (95% confidence interval 0.50 to 0.98; heterogeneity P<0.001) for angina; 1.42 (0.90 to 2.25) for fatal and non-fatal myocardial infarction, 1.32 (0.65 to 2.70) for death, 1.59 (1.09 to 2.32) for coronary artery bypass graft, and 1.29 (0.71 to 3.36; heterogeneity P<0.001) for repeated angioplasty. Differences in the methodological quality of the trials, in follow up, or in single versus multivessel disease did not explain the variability in study results in any analysis. CONCLUSIONS: Percutaneous transluminal coronary angioplasty may lead to a greater reduction in angina in patients with coronary heart disease than medical treatment but at the cost of more coronary artery bypass grafting. Trials have not included enough patients for informative estimates of the effect of angioplasty on myocardial infarction, death, or subsequent revascularisation, though trends so far do not favour angioplasty.

Angina Pectoris↗

PubMed2000

Validity of annoyance scores for estimation of long term air pollution exposure in epidemiologic studies: the Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA).

In air pollution epidemiology, estimates of long term exposure are often based on measurements made at one fixed site monitor per area. This may lead to exposure misclassification. The present paper validates a questionnaire-based indicator of ambient air pollution levels and its applicability to assess their within-area variability. Within the framework of the SAPALDIA (Swiss Study on Air Pollution and Lung Diseases in Adults) cross-sectional study (1991), 9,651 participants reported their level of annoyance caused by air pollution on an 11-point scale. This subjective measure was compared with annual mean concentrations of particulate matter less than 10 microm in diameter (PM10) and nitrogen dioxide. The impact of individual factors on reported scores was evaluated. Nitrogen dioxide concentrations at home outdoors (measured in 1993), smoking, workplace dust exposure, and respiratory symptoms were found to be predictors of individual annoyance scores. Regression of population mean annoyance scores against annual mean PM10 and nitrogen dioxide concentrations (measured in 1993 and 1991, respectively) across areas showed a linear relation and strong correlations (r>0.85). Analysis within areas yielded consistent results. The observed associations between subjective and objective air pollution exposure estimates suggest that population mean scores, but not individual scores, may serve as a simple tool for grading air quality within areas. Reported annoyance due to air pollution should be considered an indicator for a complex environmental condition and thus might be used for evaluating the implementation of environmental policies.

Adolescent↗

PubMed2000

[SAPALDIA: past, present and future].

The cross-sectional part of SAPALDIA studied the associations between respiratory symptoms or functional abnormalities and chronic exposure to a polluted environment. The results showed an elevated risk of developing respiratory symptoms in regions with higher levels of particulate matters (PM10). The same was observed with passive smoking exposure. Decreased spirometric parameters (especially FVC) were measured in areas with the highest levels of PM10. While the functional alteration is clinically minimal in the individual, the effect is significant when one considers the prevalence of an abnormal functional parameter in a general population. Exposure to pollutants at the workplace increases bronchial reactivity to non-specific stimuli, with atopy acting as amplifier of this effect. The longitudinal part of SAPALDIA examined the associations between the dynamics of respiratory symptoms or functional abnormalities and average levels, as well as short-term fluctuations, of atmospheric pollutants. It was observed that symptomatic episodes tend to last longer in more polluted regions, whichever marker of pollution is used (PM10 or NO2). Passive smoking tends to prolong respiratory symptoms and shorten asymptomatic intervals. Short-term increases in outdoor pollutants are associated with an increase in incidence of peak flows below individual baseline values. Numerous questions remain regarding the relationship between respiratory health and environment. A SAPALDIA II study is under preparation which will follow the evolution of SAPALDIA I participants with regard to respiratory symptoms, pulmonary function, bronchial reactivity and markers of atopy.

Air Pollution↗

PubMed2000

Loss of PTEN facilitates HIF-1-mediated gene expression.

In glioblastoma-derived cell lines, PTEN does not significantly alter apoptotic sensitivity or cause complete inhibition of DNA synthesis. However, in these cell lines PTEN regulates hypoxia- and IGF-1-induced angiogenic gene expression by regulating Akt activation of HIF-1 activity. Restoration of wild-type PTEN to glioblastoma cell lines lacking functional PTEN ablates hypoxia and IGF-1 induction of HIF-1-regulated genes. In addition, Akt activation leads to HIF-1alpha stabilization, whereas PTEN attenuates hypoxia-mediated HIF-1alpha stabilization. We propose that loss of PTEN during malignant progression contributes to tumor expansion through the deregulation of Akt activity and HIF-1-regulated gene expression.

Apoptosis↗

PubMed2000

Candidate genes for the hypoxic tumor phenotype.

In this study, we have analyzed changes induced by hypoxia at the transcriptional level of genes that could be responsible for a more aggressive phenotype. Using a series of DNA array membranes, we identified a group of hypoxia-induced genes that included plasminogen activator inhibitor-1 (PAI-1), insulin-like growth factor-binding protein 3 (IGFBP-3), endothelin-2, low-density lipoprotein receptor-related protein (LRP), BCL2-interacting killer (BIK), migration-inhibitory factor (MIF), matrix metalloproteinase-13 (MMP-13), fibroblast growth factor-3 (FGF-3), GADD45, and vascular endothelial growth factor (VEGF). The induction of each gene was confirmed by Northern blot analysis in two different squamous cell carcinoma-derived cell lines. We also analyzed the kinetics of PAI-1 induction by hypoxia in more detail because it is a secreted protein that may serve as a useful molecular marker of hypoxia. On exposure to hypoxia, there was a gradual increase in PAI-1 mRNA between 2 and 24 h of hypoxia followed by a rapid decay after 2 h of reoxygenation. PAI-1 levels were also measured in the serum of a small group of head and neck cancer patients and were found to correlate with the degree of tumor hypoxia found in these patients.

Animals↗