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Biomedical subjects

M S Tockman

Publications and source records attributed to M S Tockman.

At least 19 recordsLinked to original sources
PubMed1992

Considerations in bringing a cancer biomarker to clinical application.

Specific challenges face our application of emerging biomarkers to early lung cancer detection. These challenges might be considered frontiers to be bridged between established biomedical disciplines, requiring expertise often beyond the range of individual investigators. Cross-disciplinary research already has led to new appreciation of the mechanisms which underlie the phenotypic expression of the transformed cell and places within our grasp the tools which might lead to successful early lung cancer detection. Prior to the successful application of newly described markers, further cross-disciplinary research must (a) refine the selection of biologically appropriate markers, (b) validate such markers against acknowledged disease end points, (c) establish quantitative criteria for marker presence/absence, and (d) confirm marker predictive value in prospective population trials.

Biomarkers, Tumor↗
PubMed1992

Rational targets for the early detection of lung cancer.

The fact that routinely effective treatments for disseminated lung cancer are not available has prompted the search for effective early detection systems. It is important to identify lung cancer while it is still confined to the bronchial epithelium and is potentially curable with local modalities. We have previously reported on an immunologically based assay to identify antigens expressed on shed bronchial epithelial cells. This assay resulted in a statistically significant correlation of immunostaining with the eventual development of lung cancer 2-4 years prior to routine clinical detection. Attempts to further improve this approach require an understanding of the basis for its success. Based on the work of Hakomori and coworkers, this difucosylated Lewis X structure would be a likely marker of carcinogenic transformation of the bronchial epithelium. In fact, an antibody to this structure was useful for sputum immunocytochemistry analysis for early lung cancer detection. Other carbohydrate structures would also be reasonable markers to evaluate for early detection application, based on the known pattern of expression of these structures in fetal, dysplastic, and neoplastic lung tissue. Another antibody used for sputum immunostaining recognizes a 31-kd protein structure; the antibody is not a known member of a likely class of early detection targets. The reported cases of lung cancer missed by the immunostaining approach included principally adenocarcinoma of the lung, suggesting that the addition of a marker(s) of that type of morphologic differentiation should be considered. Markers to dissect the various forms of lung adenocarcinoma are being characterized and are available for evaluation in early detection applications.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗
PubMed1991

Pulmonary function and respiratory symptoms in wildland firefighters.

We studied cross-seasonal changes in pulmonary function and respiratory symptoms in 52 wildland firefighters in Northern California. The mean cross-seasonal change in forced expiratory volume in 1 second (FEV1) was -1.2% (95% confidence interval [CI] -0.5%, -2.0%) with a corresponding mean change in forced expiratory volume (FVC) of -0.3% (95% CI 0.4%, -1.0%). Decreases in FEV1 and FVC were most strongly associated with hours of recent fire-fighting activity (P = .002 and .01, respectively). When the study group was divided into three categories based on recent fire-fighting activity, firefighters in the high activity category (mean +/- SE, 73 +/- 7 hours of fire-fighting in previous week) had a -2.9% (130 mL) change in FEV1 and a -1.9% (102 mL) change in forced vital capacity (FVC). There was a significant cross-seasonal increase in most respiratory symptoms evaluated. Several symptoms (eye irritation, nose irritation, and wheezing) were associated with recent fire-fighting. These findings suggest that wildland firefighters experience a small cross-seasonal decline in pulmonary function and an increase in several respiratory symptoms. Research is under way to identify the fire conditions and specific components of exposure that produce pulmonary irritants, and to examine the potential reversibility of acute pulmonary change.

Adolescent↗
PubMed1990

Serum retinol and airway obstruction.

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.

Aged↗
PubMed1989

Biological monitoring of fire fighters: sister chromatid exchange and polycyclic aromatic hydrocarbon-DNA adducts in peripheral blood cells.

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 BPDE-DNA antigenicity than white controls (odds ratio, 3.4; 95% confidence interval, 1.08-10.5 after adjustment). Consumption of charcoal-broiled food less than 3 times a month was associated with a smaller proportion of individuals exhibiting measurable (positive) BPDE-DNA antigenicity, while consumption of broiled food greater than 3 times a month did not affect the proportion of positive individuals. Daily alcohol consumption was associated with a larger proportion of individuals exhibiting positive BPDE-DNA antigenicity, (P = 0.07). Tobacco smoking and charcoal-broiled food consumption, but not fire fighting, were associated with increased levels of baseline SCE. Sensitivity to SCE induced by mitomycin C in cultured peripheral lymphocytes was similar in fire fighter and control groups. However, sensitivity of individual fire fighters to mitomycin C-induced SCE was correlated with number of fires fought in the previous 24 h.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1989

Respiratory risk factors and mortality: longitudinal studies in Washington County, Maryland.

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) mortality are significantly more often found among subjects with ventilatory impairment (independent of smoking status). Reasons for the association of ASHD mortality with impaired forced expiration are discussed. Thus, men at increased risk for three (ASHD, lung cancer, COPD) of the five leading causes of death (three of eight for women) may be identified by spirometry. Perhaps it is time that this test was more generally applied.

Adult↗
PubMed1988

Analysis of spirometric data from a national sample of healthy 6- to 24-year-olds (NHANES II).

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 until approximately 13 yr of age. Males tended to outperform females with the same anthropometric characteristics in all age groups, except in the height range of 130 to 160 cm, where female flows and volumes were superior. Percentile growth curves were also developed to track lung development in clinical practice.

Adolescent↗
PubMed1988

Sex and race differences in the development of lung function.

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.

Adolescent↗
PubMed1988

Sensitive and specific monoclonal antibody recognition of human lung cancer antigen on preserved sputum cells: a new approach to early lung cancer detection.

Murine monoclonal antibodies (Mabs) to a glycolipid antigen of small-cell (SCC) and a protein antigen of non-small-cell lung cancer (NSCC) were applied to preserved sputum specimens from individuals who participated in The Johns Hopkins Lung Project (JHLP). In that study, undertaken in 1973 to evaluate the efficacy of sputum cytology screening, half of the high-risk participants (5,226 men, greater than or equal to 45 years of age, currently smoking greater than or equal to 1 pack of cigarettes per day) were randomly assigned to produce specimens for cytopathological analysis. During regular screenings over the next 5 to 8 years, 626 (12%) showed moderate (or greater) atypia. Sixty-nine of these (26 who progressed to cancer, 43 who did not) were randomly selected for a blinded improved Mab immunostaining protocol in the present study. Satisfactory specimens with morphologic atypia immunostained positively in 14 of the 22 patients who eventually progressed to cancer (sensitivity 64%), and were nonreactive in 35 of the 40 patients who did not progress to lung cancer (specificity 88%). Review of the true positive specimens (14/22 atypias) showed that they were collected 24 months in advance of diagnosis. In contrast, the 8/22 false negative atypias (failure to stain) showed that they were collected for an average of 57 months preceding the diagnosis of cancer. Subsequent specimens (average, 26 months before cancer) from participants who were originally considered "false negative" did stain positively improving sensitivity to 91% among specimens collected for an average of 2 years in advance of the clinical appearance of lung cancer. Specificity remained at 88%. Recognition of neoplastic antigen expression 2 years in advance of clinical cancer may be a valuable intermediate end point in studies of lung cancer prevention, detection, and therapy.

Aged↗
PubMed1988

Smoking, leukocyte count, and ventilatory lung function in working men.

Results of a cross-sectional study of ventilatory lung function (VLF) in a group of 307 working men showed that the leukocyte count in peripheral blood is more closely associated with the relative position (percentile) of a person in the frequency distribution of VLF than is smoking intensity. Leukocyte count is significantly (and inversely) correlated with VLF in nonsmokers as well as in smokers. A multiple regression analysis indicated that, after accounting for the effect of height and age, white blood cell (WBC) count explains more of the VLF variance than many other health determinants. Moreover, WBC count is the only variable, apart from height and age, that contributes significantly to the regression. Current smokers with elevated leukocyte count in peripheral blood may constitute a defined high-risk group because they demonstrate more negative regression age coefficients when compared with smokers without elevated WBC or with nonsmokers. Mechanisms that may explain these findings are discussed.

Adult↗
PubMed1987

Airways obstruction and the risk for lung cancer.

The presence of airways obstruction identify in middle-aged male smokers at increased risk for lung cancer. This hypothesis was tested in a sample of patients with moderate to severe obstruction from the Intermittent Positive Pressure Breathing Trial and a sample of patients with no obstruction to moderate obstruction from the Johns Hopkins Lung Project, all of whom were followed for the development of lung cancer. On follow-up, the risk of developing lung cancer was found to be associated with entry values for age, smoking, and ventilatory status by linear, proportional hazard, and log-linear adjustment techniques. Among cigarette smokers, the presence of airways obstruction was more of an indicator for the subsequent development of lung cancer than was age or the level of smoking. The risk for lung cancer also increased in proportion to the degree of airways obstruction. These data suggest that smokers with ventilatory obstruction are at greater risk for lung cancer than are smokers without obstruction.

Age Factors↗
PubMed1986

Sputum cytopathology: use and potential in monitoring the workplace environment by screening for biological effects of exposure.

Sputum cytopathologic monitoring detects squamous cell lung cancers at an extremely early stage (x-ray negative). It holds further potential for preventing disease by detecting epithelial alterations which reflect environmental hazards. The addition of sputum cytology screening to screening by chest x-ray film does not significantly reduce mortality from all types of lung cancer, but preliminary analysis of Johns Hopkins Lung Project data suggests that mortality from squamous cell carcinoma is reduced. Quantitative automated cytopathology systems and biochemical/immunological cell markers enhance understanding of these precursors and offer great promise for increasing capacity, accuracy, and usefulness in cytopathology screening of workers. Cytological specimens collected over years of screening workers considered at risk may be important to eventually understanding development and prevention of major occupational diseases.

Carcinoma, Squamous Cell↗
PubMed1985

Familial aggregation in chronic obstructive pulmonary disease: use of the loglinear model to analyze intermediate environmental and genetic risk factors.

To examine the contribution of environmental and genetic risk factors to familial aggregation in chronic obstructive pulmonary disease (COPD), 325 first-degree (1d) relatives and 56 spouses of 150 COPD patients were compared with 222 1d relatives and 49 spouses of 107 nonpulmonary patient controls for the prevalence of two clinical outcomes: 1) airways obstruction (AO; 1-sec forced expiratory volume less than 68% of forced vital capacity) and 2) chronic bronchitis (CB; cough and sputum for 3+ months per year for 2+ years). The loglinear model was used to study direct and indirect (ie, those mediated by other risk factors) components of familial aggregation. Three risk factors were found to be independently associated with CB and/or AO: alpha 1-antitrypsin deficiency (PiZ allele), personal cigarette smoking, and parental cigarette smoking. Because 1d relatives of COPD patients were more likely to have a PiZ allele, be heavy smokers (1+ packs per day), and be exposed to parental smoking than 1d relatives of controls, these three factors also constitute indirect components of familial aggregation. However, after controlling for the three factors, 1d relatives of COPD patients were more likely to have AO and CB than 1d relatives of controls (direct component). This direct component might have a genetic basis, because no such association was found when spouses instead of 1d relatives were compared. Thus, both shared environmental factors (personal and passive smoking) and shared genetic factors (alpha 1-antitrypsin and a possible direct genetic component) contribute to familial aggregation in COPD. The loglinear model provides a useful tool for analyzing familial aggregation in diseases of multifactorial etiology.

Biometry↗
PubMed1985

Effects of pulmonary function on mortality.

Survivorship data from a 24 year longitudinal study of 874 male volunteers in the Baltimore Longitudinal Study of Aging were used to assess the role of pulmonary function on total mortality. Even when age and smoking were considered, the ratio of forced expiratory volume in 1 sec to its predicted value was significantly associated with mortality from all causes. Individuals with poorer pulmonary function showed greater mortality during the follow-up period of this study. This relationship was also seen among never smokers in this sample, further supporting the hypothesis that impaired pulmonary function is itself a predictor of total mortality and may contribute to a number of disease processes.

Adolescent↗