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Biomedical subjects

J M Samet

Publications and source records attributed to J M Samet.

At least 91 records · Page 5Linked to original sources
PubMed1997

Non-heme (Fe3+) in the lung increases with age in both humans and rats.

Increasing non-heme iron concentrations in host tissues are potentially significant, because they can be associated with an increased risk of injury including infections, fibrosis, and neoplasms. We tested the hypothesis that non-heme (Fe3+) in the lung increases with age in both humans and rats. Human tissue was collected at autopsy before fixation occurred. The total number of specimens was 131 with 78 nonsmokers and 53 smokers. Tissue was hydrolyzed in 3 N hydrochloric acid and 10% trichloroacetic acid. Supernatant (Fe3+) was measured with a thiocyanate assay. Non-heme (Fe3+) increased with age in nonsmokers. The correlation coefficient between lung (Fe3+) and age in the nonsmokers was 0.58 (p < 0.0001). Iron stains were negative, whereas those for ferritin demonstrated increased uptake with aging. Smokers had significantly greater non-heme (Fe3+) relative to nonsmokers (101.1 and 46.0 micromol/L respectively; T = 11.44, p < 0.0001). Lung non-heme (Fe3+) in smokers also increased with age (r = 0.75; p < 0.0001). Iron stains demonstrated uptake in the proximity of retained pigmented material. Ferritin stains demonstrated intense uptake in both the macrophages and the airway and alveolar epithelium of smokers. An animal model was also analyzed for an effect of aging on lung non-heme (Fe3+). At specified times between 30 and 186 days of age, rats (n = 48) were anesthetized and exsanguinated, and the lungs were excised. In rats, similar to humans, a positive correlation was seen between lung non-heme (Fe3+) and age (r = 0.73; p = 0.007). Stains for iron in rat lung were uniformly negative, whereas those for ferritin demonstrated increased uptake by airway and alveolar epithelium in older rats. We conclude that non-heme (Fe3+) in lung tissue increases with age in both humans and rats. Elevations in lung non-heme (Fe3+) could contribute to an increased incidence of pneumonias, pulmonary fibrosis, and bronchogenic carcinoma observed among older individuals.

Adolescent↗
PubMed1997

Disruption of protein tyrosine phosphate homeostasis in bronchial epithelial cells exposed to oil fly ash.

Residual oil fly ash (ROFA) is a toxic air pollutant that we have previously shown induces inflammatory mediator expression in human bronchial epithelial cells. To identify intracellular signaling mechanisms activated by ROFA, we studied its effect on protein tyrosine phosphate metabolism in the human bronchial epithelial cell line BEAS. Noncytotoxic levels of ROFA induced significant dose- and time-dependent increases in protein tyrosine phosphate levels in BEAS cells. ROFA-induced increases in protein phosphotyrosines were associated with its soluble fraction and were mimicked by vanadyl [V(IV)]- and vanadate [V(V)]-containing solutions. Ferrous, ferric, and nickel (II) ion solutions failed to increase phosphotyrosine levels. Tyrosine phosphatase activity, which was known to be inhibited by vanadium ions, was markedly diminished after ROFA treatment. Tyrosine kinase activity was unaffected. We conclude that ROFA exposure induces vanadium ion-mediated inhibition of tyrosine phosphatase activity, leading to accumulation of protein phosphotyrosines in BEAS cells. These findings demonstrate that ROFA exposure disrupts protein tyrosine phosphate homeostasis in BEAS cells and suggest a possible mechanism that leads to increased synthesis of proinflammatory proteins in airway epithelial cells exposed to PM10.

Air Pollutants↗
PubMed1997

Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis.

We conducted a multicenter case-control study of clinically and histologically diagnosed idiopathic pulmonary fibrosis (IPF), a chronic diffuse interstitial lung disease of unknown cause. The study included 248 cases, and 491 control subjects identified through random-digit dialing, matched to cases in sex, age, and geographic region. Telephone interviews were conducted with both cases and controls to collect information on potential risk factors for IPF, including smoking and household, occupational, and environmental exposures. Pulmonary function tests, X-rays, computed tomographic (CT) scans of the chest, and lung biopsy reports were submitted by referring centers to support the diagnoses. An a priori hypothesis that smoking is associated with IPF was examined with conditional logistic regression analyses. More cases (72%) than control subjects (63%) had a history of ever smoking. The odds ratio (OR) for ever smoking was 1.6 (95% CI: 1.1 to 2.4). Risk was significantly elevated for former smokers (OR = 1.9; 95% CI: 1.3 to 2.9) and for smokers with 21 to 40 pack-yr (OR = 2.3; 95% CI: 1.3 to 3.8). A history of smoking is associated with an increased risk for the development of IPF. Although there was no clear exposure-response pattern with cumulative consumption of cigarettes, there was a trend for time since cessation of smoking, with the highest risk for those who had most recently quit.

Adult↗
PubMed1997

Ferritin expression after in vitro exposures of human alveolar macrophages to silica is iron-dependent.

The increased availability of catalytically active iron after silica exposure can present an oxidative injury to a living system. Sequestration of reactive iron would, therefore, confer a protective effect. The intracellular storage of iron by ferritin within macrophages can limit the potential for radical generation and cellular injury resulting from exposure to a metal chelate. We tested the hypothesis that in vitro exposure of human alveolar macrophages to silica increases the expression of ferritin through a posttranscriptional mechanism. Exposure of 1.0 x 10(6) macrophages to 100 microg/ml silica for 4 h increased light-subunit (L)-ferritin protein concentrations in both cell supernatants and lysates. Inclusion of 1.0 mM deferoxamine in the reaction mixtures inhibited increases in ferritin after silica. To test for a posttranscriptional regulation of ferritin protein expression, cells were incubated with acid-washed particles, silica with complexed zinc cation, and silica with complexed iron cation. L-ferritin protein concentrations were increased in both cell supernatants and lysates after 4 h of exposure to silica with complexed iron cation. There were no increases in L-ferritin after incubations with acid-washed particles or silica with complexed zinc cation. There were no significant differences in levels of L-ferritin cDNA between any of the exposures, suggesting a posttranscriptional control of ferritin expression.

Cells, Cultured↗
PubMed1997

Epidemiologic studies of ionizing radiation and cancer: past successes and future challenges.

The health effects of radiation have been a focus for research since early in the 20th century. As the century ends, extensive experimental and epidemiologic evidence has been accumulated that addresses the adverse consequences of radiation exposure; epidemiologic studies of radiation-exposed groups from the general population and specific occupational groups provide quantitative estimates of the cancer risks associated with exposure. This report provides a perspective on the extensive epidemiologic evidence on the health effects of ionizing radiation and on likely needs for further epidemiologic research on radiation and health. Epidemiologic studies have proved informative on the quantitative risks of radiation-caused cancer but we now face the challenges of more precisely characterizing risks at lower levels of exposure and also of assessing modifiers of the risks, including dose rate, genetic susceptibility, and other environmental exposures. This report considers investigative approaches, such as pooled analysis of multiple data sets, that can be used to address these complex questions and the limitations of these approaches for addressing societal concerns about the risks of radiation exposure.

Dose-Response Relationship, Radiation↗
PubMed1997

Estimating lung cancer mortality from residential radon using data for low exposures of miners.

Some recent estimates of lung cancer risk from exposure to radon progeny in homes have been based on models developed from a pooled analysis of 11 cohorts of underground miners exposed to radon. While some miners were exposed to over 10,000 working level months (WLM), mean exposure among exposed miners was 162 WLM, about 10 times the exposure from lifetime residence in an average house and about three times the exposure from lifetime residence at the "action level" suggested by the U.S. Environmental Protection Agency. The extrapolation of lung cancer risk from the higher exposures in the miners to the generally lower exposures in the home is a substantial source of uncertainty in the assessment of the risk of indoor radon. Using the pooled data for the miners, analyses of lung cancer risk were carried out on data restricted to lower exposures, either <50 WLM or <100 WLM. In the pooled data, there were 115 lung cancer cases among workers with no occupational WLM exposure and 2,674 among exposed miners, with 353 and 562 lung cancer cases in miners with <50 WLM and <100 WLM, respectively. Relative risks (RRs) for categories of WLM based on deciles exhibited a statistically significant increasing trend with exposure in each of the restricted data sets. In the restricted data, there was little evidence of departures from a linear excess relative risk model in cumulative exposure, although power to assess alternative exposure-response trends was limited. The general patterns of declining excess RR per WLM with attained age, time since exposure and exposure rate seen in the unrestricted data were similar to the patterns found in the restricted data. Risk models based on the unrestricted data for miners provided an excellent fit to the restricted data, suggesting substantial internal validity in the projection of risk from miners with high exposures to those with low exposures. Estimates of attributable risk for lung cancer (10-14%) in the U.S. from residential radon based on models from the unrestricted data were similar to estimates based on the data for miners receiving low exposures.

Air Pollutants, Radioactive↗
PubMed1997

The Sleep Heart Health Study: design, rationale, and methods.

The Sleep Heart Health Study (SHHS) is a prospective cohort study designed to investigate obstructive sleep apnea (OSA) and other sleep-disordered breathing (SDB) as risk factors for the development of cardiovascular disease. The study is designed to enroll 6,600 adult participants aged 40 years and older who will undergo a home polysomnogram to assess the presence of OSA and other SDB. Participants in SHHS have been recruited from cohort studies in progress. Therefore, SHHS adds the assessment of OSA to the protocols of these studies and will use already collected data on the principal risk factors for cardiovascular disease as well as follow-up and outcome information pertaining to cardiovascular disease. Parent cohort studies and recruitment targets for these cohorts are the following: Atherosclerosis Risk in Communities Study (1,750 participants), Cardiovascular Health Study (1,350 participants), Framingham Heart Study (1,000 participants), Strong Heart Study (600 participants), New York Hypertension Cohorts (1,000 participants), and Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study (900 participants). As part of the parent study follow-up procedures, participants will be surveyed at periodic intervals for the incidence and recurrence of cardiovascular disease events. The study provides sufficient statistical power for assessing OSA and other SDB as risk factors for major cardiovascular events, including myocardial infarction and stroke.

Adult↗
PubMed1996

Longitudinal relation between smoking and white blood cells.

Higher white blood cell counts in smokers compared with nonsmokers have been well documented, but the longitudinal relation between changes in smoking and changes in white blood cells has not been well described. Since 1984, data have been collected semiannually by the Multicenter AIDS Cohort Study (MACS), a four-center prospective cohort study of acquired immunodeficiency syndrome (AIDS) in homosexual men. The study population includes 2,435 participants who were human immunodeficiency virus (HIV) seronegative as of September 1994 and who contributed 20,918 person-visits for this analysis. For individuals who modified their smoking behavior, changes in white blood cell counts occurred primarily during the first 6 months following changes in the amount of cigarettes smoked. Among former smokers who resumed smoking, the extent of the increase in white blood cell count depended on the number of cigarettes smoked. Specifically, increases of 241, 340, and 740 cells/microliter were observed for smokers who resumed smoking < 1, 1 to < 2, and > or = 2 packs/day, respectively. Conversely, smokers who quit smoking had a decrease of white blood cell count: -32, -629, and -1,122 cells/microliter for men who previously smoked < 1, 1 to < 2, and > or = 2 packs/day, respectively. Long-term ex-smokers, however, still had higher white blood cell counts than did never smokers. There was a high within-individual correlation of white blood cell count in persons who reported a consistent level of smoking (i.e., average correlations between two white blood cell counts 6 years apart were 0.51 for never smokers, 0.48 for ex-smokers, 0.56 for men who smoked < 1 pack/day, and 0.43 for men who smoked > or = 1 pack/day). These analyses indicate an acute effect of changes in smoking on changes in white blood cell count, a residual effect of having been a smoker, and high long-term tracking for white blood cell count.

Adult↗
PubMed1996

Determinants of survival in older cancer patients.

BACKGROUND: We and others have previously described a number of characteristics that are associated with delays in diagnosis and increased risk for inadequate treatment of older women and men with cancer. These characteristics include poor social support, limited access to transportation, and impaired cognition. However, there is little information on how these factors influence survival of older cancer patients. PURPOSE: The purpose of the study was to determine which patient characteristics predicted survival up to 10 years after the diagnosis of cancer. METHODS: In 1984, we initiated a population-based study of men and women who were 65 years of age or older, living in a six-county area of New Mexico, and newly diagnosed with cancer. For 646 individuals with cancer of the breast (n = 188), prostate (n = 247), or colon or rectum (n = 211), we assessed patient baseline characteristics, disease stage at diagnosis, and adequacy of treatment (definitive or nondefinitive) as determinants of survival for up to 10 years following diagnosis. Multivariate survival models were used to analyze the data; all P values were two-sided. RESULTS: In multivariate analyses, we first included all patient characteristics, except the stage at diagnosis and the adequacy of treatment. In this initial analysis, the following were among variables that were significantly associated with patient survival: age, education, cancer knowledge, ethnic group, and cognitive status. When stage at diagnosis and adequacy of treatment were added to the model, both advanced stage at diagnosis (hazard ratio = 1.7 [95% confidence interval ¿CI¿ = 1.3-2.1] for diagnosis at regional stage versus local stage; hazard ratio = 3.0 [95% CI = 2.0-4.7] for distant stage versus local stage) and inadequate treatment (hazard ratio = 1.6 [95% CI = 1.1-2.3]) were associated with poor survival. However, adding stage at diagnosis and adequacy of treatment to the analysis had little influence on the magnitude of the effect of patient characteristics on survival. In separate analyses of patient data by cancer site, receipt of nondefinitive therapy was associated with increased mortality among patients with colon/rectal cancer (hazard ratio = 7.8 [95% CI = 2.8-21.4]) and breast cancer (hazard ratio = 2.2 [95% CI = 1.1-4.3]) but not among patients with prostate cancer (hazard ratio = 1.0 [95% CI = 0.6-1.9]). CONCLUSIONS: Advanced stage at diagnosis and inadequate treatment of older cancer patients are associated with poor survival. Impaired cognition and inadequate education in elderly patients are also associated with poor survival. This decreased survival does not appear to be a consequence of known barriers to health care that are responsible for delays in diagnosis and for inadequate treatment. IMPLICATIONS: Efforts to facilitate early diagnosis and receipt of definitive treatment for cancer in older individuals may improve their survival.

Age Factors↗
PubMed1996

Induction of prostaglandin H synthase 2 in human airway epithelial cells exposed to residual oil fly ash.

Exposure to ambient air containing respirable particulate matter at concentrations below the current National Ambient Air Quality Standard has been associated with increased rates of pulmonary-related morbidity and mortality. To identify mechanisms involved in pulmonary responses to such exposure, we studied the effects of the emission source particulate air pollutant residual oil fly ash (ROFA) on prostaglandin metabolism in cultured human airway epithelial cells. Epithelial cells exposed to ROFA for 24 hr secreted substantially increased amounts of the prostaglandin H synthase (PHS) products prostaglandins E2 and F2 alpha. The ROFA-induced increase in prostaglandin synthesis was correlated with a marked increase in PHS activity. Western blots showed that ROFA exposure induced dose-dependent increases in PHS2 protein levels. Reverse transcriptase-PCR analyses demonstrated accompanying increases in PHS2 mRNA which were evident by 2 hr of continuous exposure. In contrast, expression of PHS1 was not affected by ROFA treatment of airway epithelial cells. There were no alterations in arachidonic acid release, incorporation, or availability in ROFA-exposed cells. These data show that exposure to ROFA induces PHS2 expression, leading to increased prostaglandin synthesis in cultured airway epithelial cells. These findings suggest that prostaglandins may play a role in the toxicology of air pollution particle inhalation.

Air Pollutants↗
PubMed1996

Regional variation in survival following the diagnosis of cancer.

Recent studies have documented substantial geographical variation in patterns of treatment of cancer and other diseases. Because cancer treatment is not uniform nationwide, survival following the diagnosis of cancer might also be expected to vary geographically. Survival data from the nine population-based registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program were analyzed for cancers of the stomach, colon, rectum, lung, breast, uterus, ovary, prostate, and bladder (n = 401,861). The patients included all non-Hispanic white patients diagnosed with cancer of one of the selected sites during 1983-1991. Regional variation in crude five-year survival rates across the nine SEER areas was most marked for cancers of the uterus and prostate. For uterine cancer, for example, five-year survival ranged from 73.2% in Connecticut to 84.0% in Hawaii. Less marked variation was observed for cancers of the colon, rectum, and breast. For cancers of the bladder, ovary, stomach, and lung, survival rates five years after diagnosis were relatively invariant across the SEER areas. Observed differences in survival rates, although statistically significant, were relatively modest from the standpoint of the practicing physician. Nonetheless, the general pattern of regional variation was unchanged after adjustment for sex, age, stage, and surgical treatment and when analysis was limited to patients younger than 70 years, who would be anticipated to have the least comorbidity.

Demography↗
PubMed1996

Alterations in arachidonic acid metabolism in mouse mast cells induced to undergo maturation in vitro in response to stem cell factor.

We studied arachidonic acid (AA) metabolism during the maturation of bone marrow-derived cultured mast cells (BMCMCs) into mast cells with phenotypic characteristics, which were more similar to those of connective tissue-type mast cells. BMCMCs were maintained in medium containing 100 ng/ml recombinant rat stem cell factor (SCF) for 1 to 6 weeks. After 3 to 4 weeks in SCF, BMCMCs acquired many phenotypic characteristics of maturation, including enlarged size, numerous electron-dense cytoplasmic granules, and a 50-fold elevation in histamine content. Maintenance in SCF for 6 weeks did not significantly alter the amounts or species of eicosanoids that were produced by BMCMCs stimulated with calcium ionophore A23187. However, SCF-treated mast cells released 2.6 +/- 0.13 times more free AA and accumulated 6.4 +/- 1.0 times higher levels of intracellular free AA than did immature BMCMCs not exposed to SCF. There was no increase in the mobilization of other fatty acids (e.g., linoleic or oleic acid), indicating specificity for AA. Moreover, there were no differences between the 5-lipoxygenase activities of SCF-treated or untreated cells, as assayed in cell homogenates prepared by nitrogen cavitation. Although the total AA content in SCF-treated cells was significantly elevated, the distribution of AA in phospholipid and neutral lipid classes was not altered by SCF treatment. Total phospholipase (PL)A2 activity increased 85% +/- 11.5% in SCF-treated cells. In homogenates of immature BMCMCs, 51.0% +/- 13.7% of the PLA2 activity was inhibited by 0.5 mmol/L dithiothreitol, whereas the same concentration of dithiothreitol caused only a 2.2% +/- 10.7% reduction in the PLA2 activity in homogenates of SCF-treated BMCMCs (p < or = 0.05, n = 4). These findings suggest that SCF treatment induces a dithiothreitol-resistant PLA2 and that this PLA2 may contribute to the mobilization of AA that is not further metabolized to eicosanoids.

Animals↗
PubMed1996

Temporal and regional variability in the surgical treatment of cancer among older people.

OBJECTIVES: Numerous studies have documented that older individuals with cancer have been treated less aggressively than younger individuals. We utilized data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program to assess geographic variation in the effects of age on the surgical treatment of cancer and to examine temporal trends in the treatment of older people between 1973 and 1991. DESIGN: Ecological analyses comparing time trends of treatment in nine regions over a 19-year period. SETTING: Population-based data for nine geographic areas of the United States. PARTICIPANTS: Persons with incident cancer of the breast, colon, rectum, lung, ovary, uterus, pancreas, and stomach residing in these regions during the selected years. RESULTS: After age 64, the percentage of patients treated surgically decreased with increasing age for every cancer site studied. Between 1973 and 1991, the likelihood of receiving surgery for cancers of the uterus, colon, rectum, ovary, and breast increased more rapidly among patients ages 65 years and older than among those under age 65. This relative increase occurred consistently across most geographic areas studied. For cancers of the lung, stomach, and pancreas, the effect of age on the likelihood of receiving surgery did not diminish through the period under study.: CONCLUSIONS: Although older people remain less likely to receive surgical therapy than younger persons, for some important cancer sites the gap between the treatment of older and younger individuals narrowed from 1973 through 1991.

Age Factors↗
PubMed1996

Detection of trisomy 7 in nonmalignant bronchial epithelium from lung cancer patients and individuals at risk for lung cancer.

Early identification and subsequent intervention are needed to decrease the high mortality rate associated with lung cancer. The examination of bronchial epithelium for genetic changes could be a valuable approach to identify individuals at greatest risk. The purpose of this investigation was to assay cells recovered from nonmalignant bronchial epithelium by fluorescence in situ hybridization for trisomy of chromosome 7, an alteration common in non-small cell lung cancer. Bronchial epithelium was collected during bronchoscopy from 16 cigarette smokers undergoing clinical evaluation for possible lung cancer and from seven individuals with a prior history of underground uranium mining. Normal bronchial epithelium was obtained from individuals without a prior history of smoking (never smokers). Bronchial cells were collected from a segmental bronchus in up to four different lung lobes for cytology and tissue culture. Twelve of 16 smokers were diagnosed with lung cancer. Cytological changes found in bronchial epithelium included squamous metaplasia, hyperplasia, and atypical glandular cells. These changes were present in 33, 12, and 47% of sites from lung cancer patients, smokers, and former uranium miners, respectively. Less than 10% of cells recovered from the diagnostic brush had cytological changes, and in several cases, these changes were present within different lobes from the same patient. Background frequencies for trisomy 7 were 1.4 +/- 0.3% in bronchial epithelial cells from never smokers. Eighteen of 42 bronchial sites from lung cancer patients showed significantly elevated frequencies of trisomy 7 compared to never smoker controls. Six of the sites positive for trisomy 7 also contained cytological abnormalities. Trisomy 7 was found in six of seven patients diagnosed with squamous cell carcinoma, one of one patient with adenosquamous cell carcinoma, but in only one of four patients with adenocarcinoma. A significant increase in trisomy 7 frequency was detected in cytologically normal bronchial epithelium collected from four sites in one cancer-free smoker, whereas epithelium from the other smokers did not contain this chromosome abnormality. Finally, trisomy 7 was observed in almost half of the former uranium miners; three of seven sites positive for trisomy 7 also exhibited hyperplasia. Two of the former uranium miners who were positive for trisomy 7 developed squamous cell carcinoma 2 years after collection of bronchial cells. To determine whether the increased frequency of trisomy 7 reflects generalized aneuploidy or specific chromosomal duplication, a subgroup of samples was evaluated for trisomy of chromosome 2; the frequency was not elevated in any of the cases as compared with controls. The studies described in this report are the first to detect and quantify the presence of trisomy 7 in subjects at risk for lung cancer. These results also demonstrate the ability to detect genetic changes in cytologically normal cells, suggesting that molecular analyses may enhance the power for detecting premalignant changes in bronchial epithelium in high-risk individuals.

Aged↗
PubMed1996

Nitrogen dioxide and respiratory illness in children. Part IV: Effects of housing and meteorologic factors on indoor nitrogen dioxide concentrations.

In a prospective study of infants' exposure to nitrogen dioxide (NO2)* and respiratory illness, NO2 concentrations were measured in more than 1,400 homes in Albequerque, NM, From January 1988 through June 1991 (Health Effects Institute Research Report Number 58, Parts I, II and III). This report characterizes the variability in indoor NO2 concentrations across seasons and years, and identifies factors associated with variation in concentrations between homes and across seasons. In regression analyses of winter data, NO2 levels in the infants' bedrooms were predominately determined by the presence of gas cooking ranges with continuously burning pilot lights, the presence of wall or floor furnaces, the use of the stove for space heating, and the square footage of the living space. These findings are consistent with previously published analysis of data from homes in other U.S. cities. Relatively small differences in seasonal NO2 levels were observed across years. The correlation coefficient (r) of bedroom NO2 levels obtained in the same homes was 0.66 over two winters and 0.48 over two summers. For homes that had gas cooking ranges with continuously burning pilot lights, the NO2 bedroom concentrations differed, on average, less than 5 parts per billion (ppb) across winters. These differences were hypothesized to be caused by differences in the use of indoor NO2 sources, ventilation, and ambient (outdoor) NO2 levels. We were, however, unable to demonstrate an association between year-to-year differences in seasonal indoor NO2 concentrations and reported use of cooking range, furnace, or heater, or ambient NO2 levels, or temperature.

Air Pollution, Indoor↗