Maximum inspiratory pressure (MIP), an indicator of inspiratory muscle strength, is reported on 13,005 African-American and white participants from the Atherosclerosis Risk in Communities Study. Sex-specific associations between MIP and... more
Maximum inspiratory pressure (MIP), an indicator of inspiratory muscle strength, is reported on 13,005 African-American and white participants from the Atherosclerosis Risk in Communities Study. Sex-specific associations between MIP and age, anthropometric measures, physical activity, health status, smoking status, and education level are presented. In this cohort of subjects 47 to 68 yr of age, MIP decreased 0.93 cm H2O (p </= 0.0001) in women and 1.2 cm H2O (p </= 0.0001) in men for each 1-yr increase in age. In both sexes, after adjusting for age, the associations between MIP and current body weight, weight at 25 yr of age, waist girth, body mass index, and calf girth were statistically significant and nonlinear (convex quadratic). MIP was positively associated with standing height in both sexes after controlling for age (p </= 0.03). The age-adjusted association between MIP and sitting height was nonlinear in men and linear in women. MIP was also associated (positively) with education level, health status, physical activity, and (negatively) cigarette smoking. The study was not designed to evaluate associations with race, but data patterns suggest the absence of a race effect on MIP.
Research Interests: Anthropometry, Prospective studies, Humans, United States, Female, and 15 moreMale, Follow-up studies, American, Incidence, Risk factors, Aged, Pressure, Middle Aged, Respiratory Muscles, Spirometry, Risk Factors, Cross Sectional Studies, Inspiratory capacity, Medical and Health Sciences, and Population surveillance
If the inflammatory response to inhalation of cigarette smoke causes chronic obstructive pulmonary disease (COPD), suppression of that natural response might be beneficial. We hypothesized that a... more
If the inflammatory response to inhalation of cigarette smoke causes chronic obstructive pulmonary disease (COPD), suppression of that natural response might be beneficial. We hypothesized that a smoker's risk of developing COPD is inversely related to physiologic levels of two fatty acids that have antiinflammatory properties: eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6). The proportion of each fatty acid in plasma lipids was measured in 2,349 current or former smokers. COPD was identified and defined by clinical symptoms and/or spirometry. After adjustment for smoking exposure and other possible confounders, the prevalence odds of COPD were inversely related to the DHA (but not to the EPA) content of plasma lipid components in most of the models. For example, as compared with the first quartile of the DHA distribution, the prevalence odds ratios (ORs) for chronic bronchitis were 0.98, 0.88, and 0.69 for the second, third, and fourth quartiles, respectively (p for linear trend = 0.09). The corresponding ORs for COPD as defined spirometrically, were 0.65, 0.51, and 0.48 (p < 0. 001). Among 543 current heavy smokers, adjusted mean values of FEV1 (lowest to highest DHA quartile) were 2,706, 2,785, 2,801, and 2,854 ml. DHA may have a role in preventing or treating COPD and other chronic inflammatory conditions of the lung. Pilot testing of that hypothesis in experimental models seems warranted.
Research Interests: Humans, Human Body, Chronic Disease, Female, Male, and 15 moreAmerican, Fish consumption, Middle Aged, Odds ratio, Bronchitis, Fatty Acid, Chronic obstructive pulmonary disease, Eicosapentaenoic Acid, Docosahexaenoic Acid, Chronic Bronchitis, Experimental Model, Inflammatory response, Cell Membrane, Dietary intake, and Medical and Health Sciences
Research Interests: Biochemistry, Genetics, Pediatrics, Cancer, Magnetic Resonance Imaging, and 15 moreRisk, Technology Assessment, Preventive medicine, Public Health, Adaptive Systems, Interactions, Clinical Medicine, Medical Research, Awareness, Accuracy, Molecules, Genetic Mapping, Bandwidth, Antigens, and Cellular Communications
To present a set of novel computerized analysis algorithms to construct a computer-aided cytologic diagnosis (CACD) system to differentiate lung cancer biomarkers and identify cancer cells in the tissue-based specimen images. Molecular... more
To present a set of novel computerized analysis algorithms to construct a computer-aided cytologic diagnosis (CACD) system to differentiate lung cancer biomarkers and identify cancer cells in the tissue-based specimen images. Molecular methods, including application of cancer-specific markers, may prove to be complementary to cytology diagnosis, especially when they are combined with CACD system for biomarker assessment. We trained a novel CACD system to recognize expression of the cancer biomarkers histone H2AX in lung cancer cells and then tested the accuracy of this system to distinguish resected lung cancer from preneoplastic and normal tissues. The major characteristics of CACD algorithms is to adapt detection parameters according to cellular image contents. Our newly developed wavelet transform is able to adaptively select different resolution and orientation features based on image content requirements. Visual, statistical and quantitative results as CACD performance evaluation are presented in this paper. The presented algorithms and CACD system for cellular feature enhancement, segmentation and classification are very important in distinguishing benign and malignant lesions.
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Research Interests: Prospective studies, Humans, Female, Male, Polymerase Chain Reaction, and 15 moreConfidence intervals, Incidence, Risk factors, Aged, Middle Aged, Adult, Survival Rate, Risk Factors, Base Sequence, DNA binding proteins, Case Control Studies, Cohort Studies, Molecular Sequence Data, Medical and Health Sciences, and lung neoplasms
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Research Interests: Mass Spectrometry, Proteomics, Time-of-flight mass spectrometry, Lung Cancer, Humans, and 12 moreLaser Capture Microdissection, Clinical Sciences, Precancerous Conditions, Computerized tomography, Patient Participation, Mass Spectroscopy, Epithelial Cell Biology, Non small Cell Lung Cancer, Diagnostic Tool, High risk, mass Screening, and lung neoplasms
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ABSTRACT
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Research Interests: Cancer, Image segmentation, Features, Quantitative analysis, Lung Cancer, and 15 moreImage Classification, Linear Discriminant Analysis, Classification, Error Analysis, Feature Extraction, Cross Validation, Accuracy, Analytical Method, Biomarker, Chromosome segregation, Chromosomal Instability, Classification Accuracy, Non small Cell Lung Cancer, centrosome, and Linear discriminate analysis(Image Classification, Linear Discriminant Analysis, Classification, Error Analysis, Feature Extraction, Cross Validation, Accuracy, Analytical Method, Biomarker, Chromosome segregation, Chromosomal Instability, Classification Accuracy, Non small Cell Lung Cancer, centrosome, and Linear discriminate analysis)
(Image Classification, Linear Discriminant Analysis, Classification, Error Analysis, Feature Extraction, Cross Validation, Accuracy, Analytical Method, Biomarker, Chromosome segregation, Chromosomal Instability, Classification Accuracy, Non small Cell Lung Cancer, centrosome, and Linear discriminate analysis)
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The FEZ1/LZTS1 (FEZ1) gene, located on chromosome 8p22 (8p22), was identified recently as a candidate tumor suppressor gene. Because loss of heterozygosity at 8p21-22 is a frequent event in lung cancers, we studied FEZ1 alteration in... more
The FEZ1/LZTS1 (FEZ1) gene, located on chromosome 8p22 (8p22), was identified recently as a candidate tumor suppressor gene. Because loss of heterozygosity at 8p21-22 is a frequent event in lung cancers, we studied FEZ1 alteration in short-term cultures of resected lung cancer tumors and cell lines. We examined FEZ1 expression in 17 non-small cell lung cancer (NSCLC), 19 small cell lung cancer (SCLC) cell lines, and 6 pairs of short-term cultures of resected NSCLCs and accompanying nonmalignant bronchial cells (NBECs) by reverse transcription-PCR and Western blotting. To investigate the mechanism for silencing, cells were cultured with 5-aza-2'-deoxycytidine or trichostatin A. We screened for genomic mutations by PCR-single-strand conformational polymorphism. Thirteen of 17 NSCLC (76%) and 3 of 19 SCLC (16%) of cell lines showed absent expression (P = 0.001). Of the paired NSCLC-NBEC cultures, 3 of 6 showed loss of expression in tumor cell cultures. In the cell lines retaining e...
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Screening for lung cancer using currently available techniques is not effective in reducing mortality from the disease. Archived sputum specimens and clinical data linking specimens to lung cancer outcomes from prior screening programs... more
Screening for lung cancer using currently available techniques is not effective in reducing mortality from the disease. Archived sputum specimens and clinical data linking specimens to lung cancer outcomes from prior screening programs have been reexamined to evaluate altered gene expressing, including specific oncogene activation and tumor suppressor gene deletion, as well as genomic instability and abnormal methylation. Several of these tests allow determination of a molecular diagnosis of cancer years before clinical presentation. These sputum tests provide an impetus to reconsider screening for lung cancer. Prospective trials are required to confirm test performance characteristics, and management and intervention strategies must be developed that are appropriate to the stage at which lung cancer is diagnosed.
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To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case-control study nested in an occupational cohort of tin miners. Male workers free of cancer enrolled in the cohort. During up to 6... more
To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case-control study nested in an occupational cohort of tin miners. Male workers free of cancer enrolled in the cohort. During up to 6 years of follow-up, 339 lung cancer cases were diagnosed and, among these cases, those who donated blood prospectively (n = 108) were eligible for this study. For each case, two controls alive and free of cancer at the time of case diagnosis were matched on age and date of blood collection. Overall, we observed no association between serum alpha-tocopherol, gamma-tocopherol or selenium levels and lung cancer risk. However, a significant gradient of decreasing lung cancer risk with increasing serum alpha-tocopherol was apparent for men less than 60 years old (odds ratio by tertile: 1.0, 0.9, 0.2; trend p = 0.002). Alpha-tocopherol was also protective in men who reported no alcohol drinking (OR by tertile: 1.0, 0.6, 0.3; trend p = 0.008). Although there w...
Research Interests: Nonparametric Statistics, Environmental Monitoring, China, Mining, Lung Cancer, and 15 moreHumans, Male, Incidence, Aged, Middle Aged, Longitudinal Studies, Adult, Public health systems and services research, Case Control Study, Occupational Diseases, Logistic Models, Case Control Studies, Cohort Studies, lung neoplasms, and Epidemiological monitoring
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Research Interests: Vitamin A, Humans, Smoking, Chronic diseases, Chronic Disease, and 7 moreAnimals, Milk, Cattle, Epithelium, Adult, Bronchitis, and Drinking
The second National Health and Nutrition Examination Survey (NHANES II) incorporated spirometric examinations for a nationwide sample of individuals 6 to 24 yr of age. We analyzed spirometric data on 1,963 healthy, nonsmoking black and... more
The second National Health and Nutrition Examination Survey (NHANES II) incorporated spirometric examinations for a nationwide sample of individuals 6 to 24 yr of age. We analyzed spirometric data on 1,963 healthy, nonsmoking black and white subjects to derive prediction equations for FVC, FEV1, FEV3, PEF, Vmax50, Vmax75, and MMEF. The population was divided into three groups: children (6 to 11 yr of age); teens (males 12 to 20, females 12 to 17 yr of age); and young adults (males 21 to 24, females 18 to 24 yr of age). Using regression analysis, standing height appeared to be the most important predictor of pulmonary function across the entire age group, with the importance of the age variable decreasing in older ages. Controlling for other variables, blacks exhibited consistently lower respiratory function for most measures. This difference increased with age. Male FVC exceeded female FVC after 8 to 9 yr of age; however, female MMEF and Vmax50 performance equaled or exceeded males ...
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Risk factors for temporal changes in chronic respiratory disease mortality were evaluated from two studies conducted in Washington County, Maryland. The first examined the mortality of a private census population (greater than 35,000... more
Risk factors for temporal changes in chronic respiratory disease mortality were evaluated from two studies conducted in Washington County, Maryland. The first examined the mortality of a private census population (greater than 35,000 whites) enumerated in 1963 over two subsequent time periods by age, sex, and initial smoking status. The second examined the 10-yr mortality of a subset of the 1963 census (884 men who had undergone spirometry). We observed a fall in age-adjusted mortality from all causes and from arteriosclerotic heart disease (ASHD), but an increase in COPD mortality. However, the increase in these chronic pulmonary deaths is essentially confined to persons who were smoking cigarettes at the beginning of the study period. Furthermore, while smokers showed an increased mortality risk for all causes, the excess mortality risk did not fall uniformly across cigarette smokers. It is a major observation of this study that all-cause and cardiovascular (as well as pulmonary) ...
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The second National Health and Nutrition Examination Survey (1976 to 1980) provided spirometric examinations for a nationwide sample of individuals 6 to 24 yr of age. We analyzed spirometric data on 1,963 healthy, nonsmoking blacks and... more
The second National Health and Nutrition Examination Survey (1976 to 1980) provided spirometric examinations for a nationwide sample of individuals 6 to 24 yr of age. We analyzed spirometric data on 1,963 healthy, nonsmoking blacks and whites to examine sex and race differences in FVC, FEV1, FEV3, PEF, Vmax50, Vmax75, and mid-maximal expiratory flow (MMEF). The population was divided into three age groups: children (6 to 11), teens (males 12 to 20, females 12 to 17), and young adults (males 21 to 24, females 18 to 24). Controlling for sex, age, standing height, and body mass index, blacks had consistently lower levels of lung function for most measures. The inclusion of sitting height explained part of this reduction. Controlling for lung size using FVC as a surrogate, the performance of blacks on other spirometry measures was equal to whites in all age groups. Males tended to outperform females with the same anthropometric characteristics before the inclusion of FVC as a predictor variable. However, after controlling for lung size (FVC), female performance exceeded that of males. The higher female performance is particularly noticeable in the later flow measures. Both anatomic and physiologic factors may account for these findings.
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Fire fighters are exposed to potentially carcinogenic combustion and pyrolysis products during the course of their work. The present study was designed to test 43 fire fighters and matched controls for DNA damage which might be related to... more
Fire fighters are exposed to potentially carcinogenic combustion and pyrolysis products during the course of their work. The present study was designed to test 43 fire fighters and matched controls for DNA damage which might be related to occupational carcinogen exposures. Using peripheral blood lymphocytes, we examined (a) baseline sister chromatid exchange (SCE) frequency and (b) SCE induction by in vitro mutagenic challenge with mitomycin C. Using nucleated peripheral blood cells, we examined (c) polycyclic aromatic hydrocarbon-DNA adduct levels by assessing benzo(a)pyrene diol epoxide (BPDE)-DNA antigenicity. Exposures were determined from histories of fire-fighting activity. The presence of confounding factors (e.g., tobacco smoking, charcoal-broiled food consumption, etc.) was determined by questionnaire. Plasma cotinine levels were measured to assess recent exposures to tobacco smoke. White fire fighters exhibited a significantly higher risk for the presence of detectable BPD...
Research Interests: Cancer, Environmental Monitoring, DNA damage, DNA, Humans, and 15 moreFood Consumption, Cooking, Alcohol Drinking, Male, Alcohol Consumption, Peripheral blood lymphocyte, Adult, Biological Monitoring, Leukocytes, Cotinine, Confidence Interval, Control Group, Mitomycin, Mitomycin C, and Peripheral blood
The relation of serum retinol and carotenoids to airway obstruction was investigated in a population-based study. Respiratory symptoms and the pulmonary function of 83 white males were assessed in 1979 5 years after their blood had been... more
The relation of serum retinol and carotenoids to airway obstruction was investigated in a population-based study. Respiratory symptoms and the pulmonary function of 83 white males were assessed in 1979 5 years after their blood had been drawn. Airway obstruction in 1979, defined as a forced expiratory volume in 1 second which was equal to or less than 75% of the forced vital capacity, was associated with a decreased 1974 level of serum retinol.
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A retrospective study of the relationship of oral contraception to thrombosis was made in 104 idiopathic cases, 357 other thrombotic cases (exclusive of cerebrovascular thrombosis), and 1302 matched controls. The relative risk for... more
A retrospective study of the relationship of oral contraception to thrombosis was made in 104 idiopathic cases, 357 other thrombotic cases (exclusive of cerebrovascular thrombosis), and 1302 matched controls. The relative risk for idiopathic case users was 7.2 times that for non-users; for the whole series it was 1.9. The apparent low risk for non-idiopathic cases is considered to be due to selective prescription of this method of contraception. The risk for women using formulations containing 100 mug or more of estrogen was higher than that for users of lower doses. Among the controls, the risk of gallbladder surgery was twice as high for users as non-users. Several theoretical sources of bias were searched for and shown not to be present. Histories of oral contraceptive use were found to be accurate. A definite risk of thrombosis exists even with the low-estrogen dosage currently employed in oral contraceptive steroids.
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A comparison between prescriber records and patient-reported oral contraceptive histories obtained during a case-control study of thromboembolism and oral contraceptive use served as the basis for evaluating the extent of agreement... more
A comparison between prescriber records and patient-reported oral contraceptive histories obtained during a case-control study of thromboembolism and oral contraceptive use served as the basis for evaluating the extent of agreement between these two sources of information. Agreement between oral contraceptive user and prescriber was highest on the name of the most recently-used product (89% agreement), and dropped to 62.5% on the name of the product taken before the more recent one. For total duration of oral contraceptive use (to within one month of hospital admission), agreement (defined as differences not exceeding one month) was 36%, while 39% showed the users reporting longer duration of use, and 25% showed users reporting shorter duration. Cases showed a higher rate of agreement with prescriber records than the controls on both the name of the product and the total duration of use. Disagreement from prescriber records in the direction of reporting longer duration of use was 45...
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To predict survival of resected stage I non-small cell lung cancer (NSCLC) patients through quantitative analysis and classification of centrosome features. Disordered centrosome amplification leads to the loss of regulated chromosome... more
To predict survival of resected stage I non-small cell lung cancer (NSCLC) patients through quantitative analysis and classification of centrosome features. Disordered centrosome amplification leads to the loss of regulated chromosome segregation, aneuploidy and chromosome instability and may be a biomarker of cancer prognosis. Resected, stage I NSCLC tissues from survivor and fatal cases were immunostained with gamma-tubulin and scanned by confocal microscopy. Regions of interest were selected to include 1 cell and at least 1 centrosome. Four hundred forty-six regions were imaged, including 903 centrosomes whose features were extracted and measured. After segmentation, 12 centrosome features were measured. After optimization, 6 non-redundant features were selected for statistical analysis and classification. Two statistical methods showed that for each feature, centrosomes from survivors differed significantly from centrosomes of fatalities. Centrosomes were classified into surviva...
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To present a set of novel computerized analysis algorithms to construct a computer-aided cytologic diagnosis (CACD) system to differentiate lung cancer biomarkers and identify cancer cells in the tissue-based specimen images. Molecular... more
To present a set of novel computerized analysis algorithms to construct a computer-aided cytologic diagnosis (CACD) system to differentiate lung cancer biomarkers and identify cancer cells in the tissue-based specimen images. Molecular methods, including application of cancer-specific markers, may prove to be complementary to cytology diagnosis, especially when they are combined with CACD system for biomarker assessment. We trained a novel CACD system to recognize expression of the cancer biomarkers histone H2AX in lung cancer cells and then tested the accuracy of this system to distinguish resected lung cancer from preneoplastic and normal tissues. The major characteristics of CACD algorithms is to adapt detection parameters according to cellular image contents. Our newly developed wavelet transform is able to adaptively select different resolution and orientation features based on image content requirements. Visual, statistical and quantitative results as CACD performance evaluati...
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Monitoring respiratory epithelial biology may reveal individuals with incipient lung cancer. The expression of neuroendocrine (NE) markers in pulmonary epithelium is thought to be central to lung development, repair of injury and may... more
Monitoring respiratory epithelial biology may reveal individuals with incipient lung cancer. The expression of neuroendocrine (NE) markers in pulmonary epithelium is thought to be central to lung development, repair of injury and may contribute to carcinogenesis. In this study, we evaluate several candidate NE markers to determine the feasibility of prospective analysis of clinical specimens. The potential NE markers include the enzyme L-DOPA decarboxylase (DDC), the neuropeptide gastrin releasing peptide (GRP), and peptidyl-glycine alpha-amidating monooxygenase (PAM), the bifunctional enzyme responsible for the final bioactivation step of many neuropeptides. A comparison of PAM activity and DDC levels in 30 lung cancer cell lines indicated that peptide amidating activity may be an indicator of NE status. Bronchoalveolar lavage (BAL) fluid from subjects at risk of developing second primary lung cancer and from volunteers was obtained. The activity of the first PAM enzyme, peptidylglycine alpha-hydroxylating monooxygenase (PHM), ranged from not detectable to 507 pmol/h/mg protein in 57 specimens. The second PAM enzyme, peptidylamidoglycolate lyase (PAL), ranged from not detectable to 414 pmol/h/mg protein in 56 specimens. Using cluster analysis by the average linkage method, a group of enzyme values with PHM greater than 230 pmol/h/mg protein was determined. Long-term follow-up of these patients for new second primary lung cancers may help to determine the potential predictive value of PAM detected in the BAL fluid.
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Computed tomography (CT) screening of the chest has shown promise for early detection of lung cancer, but evidence for a reduction in lung cancer mortality by CT screening is not available. We reviewed 208 articles to synthesize available... more
Computed tomography (CT) screening of the chest has shown promise for early detection of lung cancer, but evidence for a reduction in lung cancer mortality by CT screening is not available. We reviewed 208 articles to synthesize available evidence for efficacy of CT screening in detecting potentially curative stages of lung cancer and for evidence in reducing lung cancer mortality. Other outcomes of interest included detection rate of cancer and of suspicious lesions, histology and stage of cancer at detection, screening-related morbidity, and the identification of populations uniquely suited for CT screening. We identified eight papers that reported the outcomes for CT of the chest in lung cancer screening. Since none of the studies utilized a control group, quantitative pooling was not done. In two studies, both CT and chest radiography (CXR) were used as screening tools in the same cohorts. A total of 19,107 subjects were screened using CT. The detected prevalence rate for lung c...
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Lung cancer remains the leading cause of cancer related mortality, accounting for almost one-third of cancer deaths in men and one-fourth of cancer deaths in women; 160,440 lung cancer deaths are expected in 2004. Survival from lung... more
Lung cancer remains the leading cause of cancer related mortality, accounting for almost one-third of cancer deaths in men and one-fourth of cancer deaths in women; 160,440 lung cancer deaths are expected in 2004. Survival from lung cancer depends mainly upon the stage at presentation. As localized tumors generally do not cause symptoms, the disease is usually diagnosed in symptomatic patients at advanced stages when the prognosis is poor. As a result, the overall 5-year lung cancer survival rate is only 15%. It is well known that epigenetic alterations such as DNA methylation of CpG dinucleotides located in CpG islands within the regulatory (promoter) regions of genes are associated with transcriptional silencing in cancer. Promoter hypermethylation of critical pathway genes could identify potential biomarkers for lung cancer risk. Our goal for this study is to identify novel hypermethylated genes in lung cancer. We have investigated the methylation profiles of DNA samples from 14 ...
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Although smoking is the major causal factor in the development of chronic obstructive pulmonary disease (COPD), only 10-20% of chronic heavy cigarette smokers develop symptomatic COPD, which suggests the presence of genetic... more
Although smoking is the major causal factor in the development of chronic obstructive pulmonary disease (COPD), only 10-20% of chronic heavy cigarette smokers develop symptomatic COPD, which suggests the presence of genetic susceptibility. The human microsomal epoxide hydrolase (EH) is a metabolizing enzyme which involves the process of numerous reactive epoxide intermediates and contains polymorphic alleles which are associated with altered EH activity and may be linked to increased risk for COPD. To determine whether the EH polymorphisms contributed to increased risk for COPD, prevalence of the EH codons 113 and 139 polymorphisms were compared between COPD patients and controls by a PCR-RFLP analysis using genomic DNA isolated from 131 COPD patients and 262 individually matched controls by age (+/-5 years) among Caucasians with 2:1 ratio. Significantly increased risk for COPD was observed for subjects with the EH(113His/His) genotypes (OR=2.4, 95% CI=1.1-5.1). These results were consistent with the fact that a significant trend towards increased risk was observed with predicted less protective EH codon 113 genotypes (p=0.03, trend test). A similar association was not observed for EH codon 139 polymorphism. As expected, a significant correlation between smoking dose and severity of COPD was observed (p<0.001). These results suggest that EH codon 113 polymorphism may modify risk for COPD.