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PubMed2000

Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important for establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis was analyzed by gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry. PhIP-SA and Gb adducts increased linearly with the dose. Studies on 35 volunteers with different dietary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP-SA adducts were significantly higher in meat consumers than in vegetarians (6.7 +/- 1.6 and 0.7 +/- 0.3 fmol/mg SA; respectively, mean +/- SE; p = 0.04, Mann-Whitney U test). The Gb adduct pattern was quantitatively lower but paralleled SA (3 +/- 0.8 in meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different in smokers and in non-smokers. The results show for the first time that PhIP-blood protein adducts are present in humans not given the synthetic compound. Both biomarkers appear to be suitable for assessing dietary exposure and internal PhIP dose and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases.

Animals↗
PubMed2006

Axonal damage markers in the cerebrospinal fluid of patients with clinically isolated syndrome improve predicting conversion to definite multiple sclerosis.

Clinically isolated syndrome (CIS) represents the earliest phase of multiple sclerosis (MS). This study tested whether biomarkers for axonal degeneration can improve upon sensitivity and specificity of magnetic resonance imaging (MRI) parameters in predicting conversion from CIS to MS. Patients with CIS (n = 52), relapsing-remitting MS (RRMS, n = 38) and age-matched controls (n = 25) were included. Cerebrospinal fluid (CSF) levels of tau and neurofilaments (NfHSMI35) were measured using ELISA. The MRI T2-lesion load and the Expanded Disability Status Scale (EDSS) were recorded. CSF tau and NfHSMI35 were elevated in CIS compared to controls (P<0.05). RRMS patients with acute relapse had higher NfHSMI35 levels than stable patients. Tau and NfHSMI35 levels correlated with EDSS in CIS and RRMS. In RRMS, the number of T2-lesions correlated with tau levels (R = 0.53, P = 0.01). The sensitivity predicting the conversion from CIS to MS was higher for the combination of CSF markers (either tau or NfHSMI35 elevated) than for MRI (40 versus 34%), but could be further increased to 60% if CSF and MRI criteria were combined. Similarly, the combination of tau and NfHSMI35 showed higher specificity (94%) than MRI (82%). Tau and NfHSMI35 are valuable biomarkers for axonal damage in the CIS patients. Predicting conversion from CIS to MS can be improved if CSF markers are combined with MRI.

Adolescent↗
PubMed2003

Biological markers in alcoholism.

Alcohol biomarkers include tests indicative of acute or chronic alcohol consumption (state markers), and markers of a genetic predisposition to develop alcohol dependence after chronic exposure (trait markers). While a comprehensive trait marker for alcohol dependence has not been identified, a number of successful state markers for monitoring drinking status are used clinically. These tests provide direct or indirect ways to estimate the amounts of alcohol consumed and the duration of ingestion, and to detect any harmful effects on body functions resulting from long-term misuse. The most obvious method to prove recent drinking is by demonstrating the presence of ethanol in body fluids or breath, but, because ethanol is cleared fairly rapidly from the body, this method is limited to detect only very recent drinking. Measurement of urinary 5-hydroxytryptophol or ethyl glucuronide provide more sensitive methods to disclose recent drinking, because their washout constants are much longer than for ethanol. The liver functions test (GGT, AST and ALT in serum) and the mean corpuscular volume of erythrocytes (MCV) are among the standard diagnostic tools used to identify chronic alcohol exposure. The main disadvantage with these measures is that they have low sensitivity for recent excessive intake, and that raised levels may result from several causes besides heavy drinking, implying a low specificity for alcohol. Carbohydrate-deficient transferrin (CDT), which refers to changes in the carbohydrate composition of serum transferrin, is a more specific marker for identifying excessive alcohol consumption and monitoring abstinence during outpatient treatment. The alcohol biomarkers improves knowledge of drinking patterns in both individuals and populations, and they are also valuable tools for the objective evaluation of treatment efforts. Alcohol markers have, for example, found uses in early identification of at-risk and harmful drinking, and they help to monitor abstinence and relapse in response to outpatient treatment.

Alcoholism↗
PubMed2026

MULTIPREVENT: Integrated screening for smoking-related multimorbidity using low-dose chest computed tomography.

OBJECTIVES: Tobacco consumption, combined with individual genetic predispositions, contributes to an age-dependent risk not only for lung cancer but also for other non-communicable diseases (NCDs) such as cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), osteoporosis, and diabetes. The MULTIPREVENT project aims to validate whether low-dose computed tomography (LDCT) of the chest, combined with simple biomarkers, functional tests, and genomic profiling, can serve as an effective tool for comprehensive health assessment and risk prediction of multimorbidity in adults. STUDY DESIGN: The study is based on a prospective epidemiological design involving 3000 participants from the MOLTEST-BIS lung cancer screening cohort (2016-2018). These participants, aged 50-79 years (during MOLTEST-BIS) and with a smoking history of at least 30 pack-years, will undergo two follow-up assessments in 2025-2027 and 2030-2032. METHODS: Each follow-up includes LDCT, spirometry, standardized blood pressure measurement, anthropometric evaluation, biomarker assessment (lipid profile, lipoprotein(a), glycated haemoglobin), and health-related questionnaires. Genetic profiling will be performed using the Illumina Infinium Global Screening Arrays approach to identify inherited predispositions to major NCDs. All data, clinical, imaging (including radiomics), molecular, and genetic, will be integrated through machine learning algorithms to develop AI-based risk prediction models. RESULTS: The MULTIPREVENT study is expected to generate a wide range of scientific, clinical, and infrastructural results that will serve as a foundation for future public health initiatives in integrated prevention. CONCLUSIONS: By linking imaging and biochemical markers, genetic susceptibility, and clinical parameters within a longitudinal design, MULTIPREVENT will establish data-driven, AI-supported prevention strategies aimed at reducing morbidity and mortality among adults exposed to tobacco. The project will also serve as a model for population-based multimorbidity prevention programs.

Humans↗
PubMed2002

The prognostic molecular markers in hepatocellular carcinoma.

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.

Apoptosis↗
PubMed2002

Respiratory hypersensitivity to trimellitic anhydride in Brown Norway rats: evidence for different activation pattern of immune cells following topical and respiratory induction.

The elicitation of respiratory allergy in animal models is exquisitely complex and interpretation of results from different laboratories cannot readily be compared due to variability in testing protocols, biomarkers and techniques used to identify 'positive' responses. On the one hand, guinea-pigs have been proposed as a good model with which to study allergic and irritant bronchial hyperresponsiveness. On the other hand, considerable efforts have been made to develop animal models that take the immunological mechanisms into account to reduce the complexity as well as duration of the guinea-pig assays. In principle, local skin reactions can easily be determined by the local lymph node assay (LLNA) introduced by Kimber and Weisenberger. In contrast to lung sensitization there are already simplified and reliable models available to test for and discriminate contact sensitizers from skin irritants, i.e. the modified local lymph node assay IMDS (integrated model for the differentiation of skin reactions). Modifications of this assay verified that methods other than radioactive labelling may be comparably sensitive, and that it is possible to eliminate 'false positive' results induced by irritants (IMDS). Thus, we asked whether there could be a similar simplified model like the modified LLNA or IMDS for investigations of respiratory allergens. Therefore, we analysed immune reactions induced by the dermal and respiratory route, respectively. Analyses of the draining lymph nodes of the lung and the ear were carried out before and after challenge via the pulmonary tract. The results clearly support that (1) the reactions in the lung draining lymph nodes could be used as early indicators of respiratory sensitization, and (2) the specificity of the immune competent cells seem to be dependent of the route of administration during induction.

Administration, Inhalation↗
PubMed2005

Sport-related differences in biomarkers of bone resorption and cartilage degradation in endurance athletes.

OBJECTIVE: By measuring urinary cross-linked N-telopeptide (NTx) as a bone resorption marker and urinary C-telopeptide of type II collagen (CTx-II) as a cartilage degradation marker, we asked whether differences in skeletal stresses in college athletes undergoing high-intensity training for diverse types of aerobic sports affect their skeletal metabolism and, if so, differentially or in unison. METHODS: The study was cross-sectional at a Division 1 college campus with 60 student athletes representing crew, cross-country running and swimming. Controls were 16 non-athlete undergraduates. Urine samples were collected for NTx and CTx-II analysis by enzyme-linked immunosorbent assay, normalizing results to creatinine. Two-way analysis of variance models and pair-wise comparisons were used to test whether biomarker levels differed by sport and the significance when adjusted for body mass index (BMI). RESULTS: NTx and CTx-II showed significant differences between groups before and after adjusting for BMI. NTx was highest in the rowers, and higher in rowers and runners than in swimmers or controls. CTx-II was significantly higher in runners than in crew, swimmers or controls, when unadjusted for BMI. After adjusting for BMI, these group differences remained significant except for runners over crew. CONCLUSION: Athletes in-training in the three sports show significant differences in these markers of bone resorption and cartilage collagen degradation. The results suggest that crew undergo the highest bone remodeling and runners the highest cartilage degradation. The results also show how these markers can vary physiologically between individuals, at extremes of skeletal exercise.

Adolescent↗
PubMed2006

PCBs exert an estrogenic effect through repression of the Wnt7a signaling pathway in the female reproductive tract.

Polychlorinated biphenyls (PCBs) have been proposed to have a weak estrogenic activity and therefore pose a risk as potential environmental endocrine disruptors to the perinatal development of the female reproductive tract. Perinatal exposure to high concentrations of the potent synthetic estrogen diethylstilbestrol (DES) induces abnormal development of the female reproductive tract via a mechanism that acts through the down-regulation of Wnt7a (wingless-type MMTV integration site family, member 7A). To test the hypothesis that PCBs act as weak estrogens, we injected neonatal mice with a commercial PCB mixture (Aroclor 1254) or with low levels of DES and measured effects of exposure on Wnt7a expression and uterine morphology. We report here that neonatal PCB or low-level DES exposure resulted in the down-regulation of Wnt7a expression. In addition, both PCB and low-level DES exposure induced changes in the uterine myometrium and gland formation. These data reveal that weak estrogens such as the PCBs act through a Wnt7a-dependent pathway and suggest that Wnt7a regulation is a sensitive biomarker for testing weak estrogenic candidate compounds. The morphologic changes that were elicited by PCBs and DES were different immediately after exposure, suggesting that Wnt7a-independent pathways are also activated by one or both of these compounds. Although Wnt7a down-regulation is transient after estrogenic exposure, subsequent morphologic changes became more pronounced during postnatal and adult life, suggesting that the female reproductive tract is permanently reprogrammed after exposure even to weak estrogenic compounds. In addition, Wnt7a heterozygous mice were more sensitive to PCB exposure, revealing an important genetic predisposition to risks of environmental endocrine disruptors.

Animals↗
PubMed2003

Induction of cytochrome P-450 activity in individual Chironomus riparius Meigen larvae exposed to xenobiotics.

Cytochrome P450 activity in individual Chironomus riparius larvae was measured using a microtiter plate adaptation of the ethoxyresorufin-O-deethylase (EROD) assay. The sensitivity of this biomarker was tested by exposing larvae to phenobarbital (0.5 and 1.0 mM) and permethrin (1 and 10 microg/g). Both chemicals induced EROD activity in C. riparius larvae by up to 1.58-fold with PB and 2.47-fold with permethrin. EROD induction was more pronounced after 48 h. The initially high EROD activity in the controls suggested that P450s are induced by stress. Feeding levels prior to exposure also had a significant effect on EROD activity. EROD activity compared to the control was highest when larvae were fed double the normal ration. These results indicate that EROD activity in individual C. riparius may be a useful biomarker to add to a suite of biomarkers for the detection of freshwater pollution.

Animals↗
PubMed2005

Effect of algal and bacterial diet on methyl mercury concentrations in zooplankton.

We studied the effect of zooplankton diet on MeHg accumulation in different zooplankton size-fractions from lakes of different trophic status. Using fatty acid biomarkers, we tested the hypotheses that (a) variations of MeHg concentrations are determined bythe taxonomic composition of zooplankton and (b) concentrations of dietary algal and bacterial compounds can predict MeHg concentrations of seston (10-64 microm), micro- (100-200 microm), meso- (200-500 microm), and macrozooplankton (>500 microm) in lakes on Vancouver Island, Canada. MeHg concentrations increased from seston (4-48 ng g dry weight(-1)) to macrozooplankton (94-240 ng g dry weight(-1)), indicating that MeHg accumulated as a function of plankton size. Results from linear regression analysis showed that MeHg concentrations were not significantly related to the taxonomic composition of zooplankton. However, using dietary lipid biomarkers, we demonstrated that bacterial diet (R2 = 0.50; p < 0.01) could better predict variations of MeHg concentrations in zooplankton than essential algal diet (R2 = 0.35; p < 0.01). Because MeHg accumulation within the planktonic food web was higher (20x) than the observed accumulation of total bacterial (6.5x) and algal (4.7x) diet biomarkers, zooplankton retained dietary MeHg more efficiently than bacterial and algal diet compounds. These results indicate that MeHg of macrozooplankton, the preferred prey size of planktivorous fish, is more efficiently transferred than essential diet compounds to organisms at higher trophic levels.

Animal Feed↗
PubMedDate not supplied

The potential of the three-spined stickleback (Gasterosteus aculeatus L.) as a combined biomarker for oestrogens and androgens in European waters.

The majority of endocrine disruption studies in Europe have been on non-indigenous species (some of them tropical!)--and none of which has traits that make them suitable for the detection of androgenic compounds. To overcome these problems, we have been developing the stickleback as a model biomarker for testing the effect of endocrine disrupters in European waters. Its advantages are: it is the only fish with a quantifiable in vivo androgen and anti-androgen endpoint (the production of the glue protein, spiggin, by the kidney); it is the only fish in which it will be possible to simultaneously test oestrogenic and androgenic properties of compound; it has a genetic sex marker; it is found in all EU countries; it survives and breeds in both seawater and freshwater; it is extremely robust and can be readily deployed in situ; it displays a variety of pronounced reproductive behaviours; it has a simple and short life cycle, low fecundity and high egg/fry survival rates.

Androgens↗
PubMed2001

The use of biomarkers in Daphnia magna toxicity testing V. In vivo alterations in the carbohydrate metabolism of Daphnia magna exposed to sublethal concentrations of mercury and lindane.

Aspects of the carbohydrate metabolism of Daphnia magna exposed for 48 and 96 h to sublethal concentrations of mercury and lindane were investigated. General as well as toxicant-specific perturbations in the intermediary metabolism were observed. Both model toxicants caused an increase in glycolytic and hexose-monophosphate shunt activity. Mercury exposure increased lactate dehydrogenase and isocitrate activity (only after 96 h), while lindane exposure, on the contrary, inhibited the cellular lactate formation and increased the Krebs' cycle activity (only after 48 h). Daphnids exposed to sublethal mercury concentrations clearly exhibited increased glycogenolytic activity, while in lindane-exposed organisms mainly glycogen phosphorylase inhibition was detected. The short-term enzyme-based effect levels (48--96 h LOEC and EC(10) values) were compared with the effects on the population dynamics. This evaluation for both model toxicants suggests that threshold levels (LOEC or EC(10) values) based on pyruvate kinase activity after 48 and 96 h of exposure could be potential early warning signals for long-term effects. A set of enzymatic endpoints, based on the intermediary metabolism, is suggested to characterize the metabolic state of the daphnids.

Animals↗
PubMed2004

[Controversies in the Bethesda System. To diagnose atypical squamous cells of undetermined significance (ASCUS) or not to diagnose?].

The classification of pap smears according to the Bethesda System introduced to the cytologic diagnostics atypical squamous cells of undetermined significance (ASCUS). From the moment of the introduction this term arises many controversies because morphological criteria proposed for the determining ASCUS are very subjective. Even most experienced cytologists not always are able to correct diagnosis of ASCUS. There are also doubts in the clinical procedure connected with the recognition ASCUS. To diminish doubts to the minimum appeared several proposals categorization of ASCUS. The cytologic diagnosis of ASCUS is a serious dilemma both clinical and considerable economic problem. There are suggestions of the elimination from the Bethesda System recognition ASCUS. Many authors it maintains that there is no reason to qualify atypical cells as ASCUS because it can be an image of the occurrence cervical intraepithelial neoplasia (CIN). The hope is that the three-dimensional microscopy, HPV DNA testing, cellular biomarkers, involvement of the cytology to colposcopic research considerably will decrease the number of incorrect diagnoses of ASCUS with the advantage for the clinical procedure. In light of opinions introduced in this paper it appears that the diagnostics ASCUS is legitimate. It is necessary to perform precise microscopic analysis of morphology observed cellules. The recognition of ASCUS one ought to place only exceptionally remembering simultaneously about clinical consequences of such diagnosis.

Carcinoma, Squamous Cell↗
PubMed1995

Two-dimensional protein electrophoresis and multiple hypothesis testing to detect potential serum protein biomarkers in children with fetal alcohol syndrome.

Fetal alcohol syndrome (FAS) surveillance and intervention efforts are hampered by the lack of a specific biochemical test for diagnosis of the syndrome. Based on the hypothesis that abnormalities in growth and development (key features of FAS) involve altered protein metabolism, we analyzed serum proteins by two-dimensional gel electrophoresis and image analysis to search for potential protein biomarkers of FAS. Serum samples from 12 participants in whom FAS had been diagnosed and 8 sex- and age-matched participants whose mothers did not consume alcohol were analyzed in duplicate to determine whether the integrated intensities of matched proteins are significantly altered in children with FAS. Multiple hypothesis testing on 34 of the gels consisting of more than 1700 spots per gel revealed 21 proteins that we classified as potential protein biomarkers of FAS on the basis of significant t-test differences at p < 0.02. We classified 8 of the proteins as candidate biomarkers on the basis of significant concentration differences between case and control subjects at p < 0.01. One of the proteins is clearly an isoform of retinol binding protein; two appear in the area of the gel where alcohol dehydrogenase is expected to appear; one appears to be an isoform of alpha-1-antitrypsin; three appear to be isoforms of the beta-chain of haptoglobin; three may be forms of immunoglobulin light chains; and several others have not been associated with known proteins. No single protein differentiated all case subjects from control subjects, but stepwise canonical discriminant analyses revealed four groups of spots that distinguished between FAS case and control subjects with no misclassifications.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1998

Induction of apoptosis and down-regulation of bcl-6 in mutu I cells treated with ethanolic extracts of the Chinese herbal supplement PC-SPES.

PC-SPES, an HPLC-standardized 8-herb dietary supplement prepared by proprietary extraction/mixing technologies, appears to have a number of health benefits when given to cancer patients. These include reduction of serum PSA (prostate specific antigen) in individuals diagnosed with advanced prostate carcinoma, and overall improvement of morbidity and immune status in terminal cancer cases. Since the expression of bcl-6 in T and B lymphocytes has been reported to be significantly down regulated by mitogens, we reason that the immune boosting effects of PC-SPES could involve the modulation of bcl-6 expression. Such a hypothesis was tested in the bcl-6 abundant Mutu I cells. Specifically, we investigated the effects of PC-SPES in regulating cell growth, induction of apoptosis, effecting changes in the retinoblastoma gene RB and the modulation of expression of the bcl-6. Herein we report that proliferation of Mutu I cells was inhibited by a 3-7 day incubation with ethanolic extracts of PC-SPES, with concurrent induction of apoptosis. In addition, a dose-dependent reduction of bcl-6 was observed, with no concomitant change in either the phosphorylated or the unphosphorylated forms of RB. These data raise the possibility that PC-SPES may enhance immune functions in vivo by down-regulating bcl-6 expression. Alternatively, decrease in bcl-6 could serve as a biomarker for testing the efficaciousness of PC-SPES in vivo.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Chronic prenatal ethanol exposure and increased concentration of fatty acid ethyl esters in meconium of term fetal Guinea pig.

In humans, the occurrence of prenatal exposure to ethanol is difficult to validate objectively. Increased concentration of fatty acid ethyl esters (FAEE) in the meconium of the newborn may be a biomarker of prenatal ethanol exposure. The validity of this proposed biomarker was tested in pregnant guinea pigs that received chronic oral administration of 4 g ethanol/kg maternal body weight/day (n=8), isocaloric-sucrose/pair-feeding (n=8) or water (n=2) throughout gestation. At gestational day 65 (term, gestational day 66 to 69), each dam and her offspring were euthanized, and meconium was collected from the term fetal large intestine. Eight individual FAEE (lauric, myristic, palmitic, palmitoleic, stearic, oleic, linolenic and arachidonic AEE) were measured by gas chromatography--flame ionization detection and confirmed by gas chromatography--mass spectrometry. The chronic maternal ethanol regimen decreased fetal body weight and brain weight. There was virtually no measurable FAEE in the meconium for the water group (n=3 fetuses). For meconium of the ethanol offspring (n=25 fetuses) compared with the sucrose offspring (n=23 fetuses), the total FAEE concentration was 8-fold higher; and lauric, palmitic, stearic and oleic AEE concentrations were at least 5-fold higher for the ethanol group. The data indicate that fetal meconium FAEE constitute a biomarker of prenatal ethanol exposure for a maternal ethanol regimen that restricts fetal development, with an inverse relationship between meconium total FAEE concentration and both body weight and brain weight.

Animals↗
PubMed1997

Assessment of respiratory effect of air pollution: study design on general population samples.

The aim of this paper is to describe an epidemiological model to investigate the relationship between respiratory diseases and environmental air pollution. In the Po Delta prospective study, subjects were investigated before and after a large thermoelectric power plant began operating, in 1980 to 1982 and in 1988 to 1991, respectively. The Pisa prospective study was performed in 1986 to 1988 and in 1991 to 1993, before and after the construction of a new expressway that encircles the city from the North to the Southeast. In each survey, subjects completed the interviewer-administered standardized CNR questionnaire on respiratory symptoms/diseases and risk factors, and performed lung function tests. In the second survey of each study, skin prick tests, total serum IgE determination, methacholine challenge test and biomarkers (such as sister chromatide exchanges, micronuclei, chromosomal abnormalities, DNA and hemoglobin adducts) were also performed. Concentrations of total suspended particulate and SO2 in both surveys were higher in urban than in rural areas, as well as symptom/disease prevalences and bronchial reactivity. Subgroups of subjects from the two samples were enrolled to perform a specific study on the acute respiratory effects of indoor pollution; the daily presence of symptoms and measurements of peak expiratory flow (PEF), daily activity pattern, and assessment of the indoor air quality (particulates < 2.5 mu and NO2) were evaluated. Higher symptom prevalences and PEF variability level were observed in subjects with the highest levels of NO2 or particulates, especially asthmatics. In conclusion, these studies represent a basis for further analyses to better define the relationship between respiratory health and indoor/outdoor pollutant levels.

Adolescent↗
PubMed2005

Tumor-specific p53 sequences in blood and peritoneal fluid of women with epithelial ovarian cancer.

OBJECTIVE: Free tumor DNA in body fluids may be an important biomarker. We tested whether tumor-specific mutated p53 DNA can be detected in blood and peritoneal fluid from women with epithelial ovarian cancer. STUDY DESIGN: Sequencing of tumor DNA identified somatic p53 mutations. Free DNA from matched blood or peritoneal fluid was evaluated for the tumor-specific p53 mutation using a ligase detection reaction. RESULTS: Sixty-nine of 137 tumors (50%) had p53 mutations. Plasma or serum from 21 (30%) of the 69 informative cases contained the tumor-specific p53 mutation. Circulating tumor was an independent predictor of decreased survival in multivariate analysis (P=.02). We detected tumor DNA in peritoneal fluid in 28 of 30 (93%) cases, including all 6 cases with negative cytology. CONCLUSION: One third of women with ovarian cancer have circulating tumor DNA and an associated reduced survival. Free tumor DNA can be detected in the majority of peritoneal fluid samples.

Ascitic Fluid↗