Journal of Cancer Research and Clinical Oncology, 1991
We have proposed that cellular senescence is controlled by normal genes that are activated or who... more We have proposed that cellular senescence is controlled by normal genes that are activated or whose functions become manifest at the end of the life span of a cell. Defects in these genes allow cells to escape senescence and become immortal. Senescence genes have ...
Journal of Cancer Research and Clinical Oncology, 1991
We have proposed that cellular senescence is controlled by normal genes that are activated or who... more We have proposed that cellular senescence is controlled by normal genes that are activated or whose functions become manifest at the end of the life span of a cell. Defects in these genes allow cells to escape senescence and become immortal. Senescence genes have ...
Phosgene, a toxic gas widely used as an industrial chemical intermediate, is known to cause life-... more Phosgene, a toxic gas widely used as an industrial chemical intermediate, is known to cause life-threatening latent noncardiogenic pulmonary edema. Mechanisms related to its toxicity appear to involve lipoxygenase mediators of arachidonic acid (AA) and can be inhibited by pretreatment with drugs that increase adenosine 3′,5′-cyclic monophosphate (cAMP). In the present study, we used the isolated buffer-perfused rabbit lung model to investigate the mechanisms by which cAMP protects against phosgene-induced lung injury. Posttreatment with dibutyryl cAMP (DBcAMP) was given 60-85 min after exposure by an intravascular or intratracheal route. Lung weight gain (LWG) was measured continuously. AA metabolites leukotriene (LT) C4, LTD4, and LTE4 and 6-ketoprostaglandin F1 alpha were measured in the perfusate at 70, 90, 110, 130, and 150 min after exposure. Tissue malondialdehyde and reduced and oxidized glutathione were analyzed 150 min postexposure. Compared with measurements in the lungs o...
Advancements in the quality and availability of highly sensitive analytical instrumentation and m... more Advancements in the quality and availability of highly sensitive analytical instrumentation and methodologies have led to increased interest in the use of microsamples. Among microsamples, dried blood spots (DBS) are the most well-known. Although there have been a variety of review papers published on DBS, there has been no attempt at describing the full range of analytes measurable in DBS, or any systematic approach published for characterizing the strengths and weaknesses associated with adoption of DBS analyses. A scoping review of reviews methodology was used for characterizing the state of the science in DBS. We identified 2018 analytes measured in DBS and found every common analytic method applied to traditional liquid samples had been applied to DBS samples. Analytes covered a broad range of biomarkers that included genes, transcripts, proteins, and metabolites. Strengths of DBS enable its application in most clinical and laboratory settings, and the removal of phlebotomy and...
Clinics in Occupational and Environmental Medicine
... Baltimore, MD 21205, USA. email address ,; Rex C Yung, MD: Affiliations. Department of Medici... more ... Baltimore, MD 21205, USA. email address ,; Rex C Yung, MD: Affiliations. Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. ,; Paul Strickland, PhD: Affiliations. Departments of Epidemiology and ...
Most smoke-free legislation to reduce secondhand smoke (SHS) exposure exempts waterpipe (hookah) ... more Most smoke-free legislation to reduce secondhand smoke (SHS) exposure exempts waterpipe (hookah) smoking venues. Few studies have examined SHS exposure in waterpipe venues and their employees. We surveyed 276 employees of 46 waterpipe tobacco venues in Istanbul, Moscow, and Cairo. We interviewed venue managers and employees and collected biological samples from employees to measure exhaled carbon monoxide (CO), hair nicotine, saliva cotinine, urine cotinine, urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and urine 1-hydroxypyrene glucuronide (1-OHPG). We estimated adjusted geometric mean ratios (GMR) of each SHS biomarker by employee characteristics and indoor air SHS measures. There were 73 non-smoking employees and 203 current smokers of cigarettes or waterpipe. In non-smokers, the median (interquartile) range concentrations of SHS biomarkers were 1.1 (0.2, 40.9) µg/g creatinine urine cotinine, 5.5 (2, 15) ng/mL saliva cotinine, 0.95 (0.36, 5.02) ng/mg hair nicotine, 1.48 (0.98, 3.97) pg/mg creatinine urine NNAL, 0.54 (0.25, 0.97) pmol/mg creatinine urine 1-OHPG, and 1.67 (1.33, 2.33) ppm exhaled CO. An 8-hour increase in work hours was associated with higher urine cotinine (GMR: 1.68, 95% CI: 1.20, 2.37) and hair nicotine (GMR: 1.22, 95% CI: 1.05, 1.43). Lighting waterpipes was associated with higher saliva cotinine (GMR: 2.83, 95% CI: 1.05, 7.62). Non-smoking employees of waterpipe tobacco venues were exposed to high levels of SHS, including measurable levels of carcinogenic biomarkers (tobacco-specific nitrosamines and PAHs). Smoke-free regulation should be extended to waterpipe venues to protect non-smoking employees and patrons from the adverse health effects of SHS.
Journal of exposure science & environmental epidemiology, 2017
Polycyclic aromatic hydrocarbons (PAHs), the by-products of incomplete combustion of organic mate... more Polycyclic aromatic hydrocarbons (PAHs), the by-products of incomplete combustion of organic materials, are commonly found on particulate matter (PM) and have been associated with the development of asthma and asthma exacerbation in urban populations. We examined time spent in the home and outdoors as predictors of exposures to airborne PAHs and measured urinary 1-hydroxypyrene-glucuronide (1-OHPG) as internal dose of PAHs in 118 children aged 5-12 years from Baltimore, MD. During weeklong periods (Saturday-Saturday) in each of four seasons: daily activities were assessed using questionnaires, indoor air nicotine and PM concentrations were monitored, and urine specimens were collected on Tuesday (day 3) and Saturday (day 7) for measurement of 1-OHPG. Time spent in non-smoking homes was associated with significantly decreased 1-OHPG concentration in urine (β=-0.045, 95% CI (-0.076, -0.013)), and secondhand smoke (SHS) exposures modified these associations, with higher urinary 1-OHPG ...
Http Dx Doi Org 10 1080 15287390252808028, Jan 7, 2011
The association between urinary 1-hydroxypyrene glucuronide (1-OHPG) levels, as an internal measu... more The association between urinary 1-hydroxypyrene glucuronide (1-OHPG) levels, as an internal measure of polycyclic aromatic hydrocarbon (PAH) exposure, and glycophorin A (GPA) mutation frequency, as an early biologic effect indicator, was determined to establish whether genetic polymorphisms of glutathione S-transferase (GST) isoforms GSTM1 and GSTT1 play a role. Eighty-one workers including 38 employees directly involved in incinerating industry wastes were recruited from a company located in South Korea. Urinary 1-OHPG levels were measured by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11. Erythrocyte GPA variant frequency (NN or NO) was assessed in MN heterozygotes with a flow cytometric assay. The GSTM1 and GSTT1 genotypes were assessed by a multiplex polymerase chain reaction (PCR) method. Urinary 1-OHPG levels were higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs. An increase was seen in GPA variant frequency levels with increase in urinary 1-OHPG levels. When this association was evaluated by GSTM1 genotype status, the association between GPA mutation and urinary 1-OHPG levels was stronger in individuals with GSTM1 genotype. These results suggest that the association between urinary 1-OHPG and GPA mutation might be modulated by the GSTM1 genotype.
Journal of Occupational and Environmental Medicine, Oct 1, 1998
5-Aminolevulinic acid (ALA) is the first intermediate substrate in the heme synthetic pathway and... more 5-Aminolevulinic acid (ALA) is the first intermediate substrate in the heme synthetic pathway and is the substrate of aminolevulinic acid dehydratase (ALAD, porphobilinogen synthase). Because lead effectively inhibits ALAD activity, resulting in accumulation of ALA in urine and blood, urinary ALA (ALAU) has been used as a biomarker for lead exposure or early biologic effect of lead. Intraindividual variation in urinary excretion of ALA requires the use of 24-hour urine samples or adjustment of single urine samples by other normalizing variables, such as urinary creatinine concentration. Previous studies of ALAU concentration have used various adjustment methods; however, few have compared creatinine-adjusted ALAU concentration with ALA concentration in plasma (ALAP) from subjects with low (< 30 micrograms/dL) to moderate (< 60 micrograms/dL) levels of blood lead. To determine if creatinine-adjusted ALAU is associated with ALAP, we measured ALAU, ALAP, and urinary creatinine in 65 Korean lead workers with blood lead concentrations in the range of 14-60 micrograms/dL. ALAU, ALAU/creatinine, or ALAU/log creatinine all correlated with ALAP. However, ALAU/creatinine correlated more closely with ALAP based on Spearman's r (rs = 0.40, P, = 0.0009), supporting the use of ALA/creatinine in single urine samples as a surrogate for ALAP.
Cancer Epidemiology Biomarkers Prevention a Publication of the American Association For Cancer Research Cosponsored By the American Society of Preventive Oncology, Jun 1, 1999
Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis, Aug 17, 2005
Cross-sectional biomarker studies can provide a snapshot of the frequency and characteristics of ... more Cross-sectional biomarker studies can provide a snapshot of the frequency and characteristics of exposure/disease in a population at a particular point in time and, as a result, valuable insights for delineating the multi-step association between exposure and disease occurrence. Three major issues should be considered when designing biomarker studies: selection of appropriate biomarkers, the assay (laboratory validity), and the population validity of the selected biomarkers. Factors related to biomarker selection include biological relevance, specificity, sensitivity, biological half-life, stability, and so on. The assay attributes include limit of detection, reproducibility/reliability, inter-laboratory variation, specificity, time, and cost. Factors related to the population validity include the frequency or prevalence of markers, greater inter-individual variation than intra-individual variation, intra-class correlation coefficients (ICC), association with potential confounders, invasiveness of specimen collection, and subject selection. Three studies are selected to demonstrate different features of cross-sectional biomarker studies: (1) characterizing the determinants of the biomarkers (study I: urinary PAH metabolites and environmental particulate exposure), (2) relationship of multiple biomarkers of exposure and effect (study II: relationship between urinary PAH metabolites and oxidative stress), and (3) evaluating gene-environmental interaction (study III: effect of genetic polymorphisms of GSTM1 on the association of green tea consumption and urinary 1-OHPG levels in shipbuilding workers).
Journal of Cancer Research and Clinical Oncology, 1991
We have proposed that cellular senescence is controlled by normal genes that are activated or who... more We have proposed that cellular senescence is controlled by normal genes that are activated or whose functions become manifest at the end of the life span of a cell. Defects in these genes allow cells to escape senescence and become immortal. Senescence genes have ...
Journal of Cancer Research and Clinical Oncology, 1991
We have proposed that cellular senescence is controlled by normal genes that are activated or who... more We have proposed that cellular senescence is controlled by normal genes that are activated or whose functions become manifest at the end of the life span of a cell. Defects in these genes allow cells to escape senescence and become immortal. Senescence genes have ...
Phosgene, a toxic gas widely used as an industrial chemical intermediate, is known to cause life-... more Phosgene, a toxic gas widely used as an industrial chemical intermediate, is known to cause life-threatening latent noncardiogenic pulmonary edema. Mechanisms related to its toxicity appear to involve lipoxygenase mediators of arachidonic acid (AA) and can be inhibited by pretreatment with drugs that increase adenosine 3′,5′-cyclic monophosphate (cAMP). In the present study, we used the isolated buffer-perfused rabbit lung model to investigate the mechanisms by which cAMP protects against phosgene-induced lung injury. Posttreatment with dibutyryl cAMP (DBcAMP) was given 60-85 min after exposure by an intravascular or intratracheal route. Lung weight gain (LWG) was measured continuously. AA metabolites leukotriene (LT) C4, LTD4, and LTE4 and 6-ketoprostaglandin F1 alpha were measured in the perfusate at 70, 90, 110, 130, and 150 min after exposure. Tissue malondialdehyde and reduced and oxidized glutathione were analyzed 150 min postexposure. Compared with measurements in the lungs o...
Advancements in the quality and availability of highly sensitive analytical instrumentation and m... more Advancements in the quality and availability of highly sensitive analytical instrumentation and methodologies have led to increased interest in the use of microsamples. Among microsamples, dried blood spots (DBS) are the most well-known. Although there have been a variety of review papers published on DBS, there has been no attempt at describing the full range of analytes measurable in DBS, or any systematic approach published for characterizing the strengths and weaknesses associated with adoption of DBS analyses. A scoping review of reviews methodology was used for characterizing the state of the science in DBS. We identified 2018 analytes measured in DBS and found every common analytic method applied to traditional liquid samples had been applied to DBS samples. Analytes covered a broad range of biomarkers that included genes, transcripts, proteins, and metabolites. Strengths of DBS enable its application in most clinical and laboratory settings, and the removal of phlebotomy and...
Clinics in Occupational and Environmental Medicine
... Baltimore, MD 21205, USA. email address ,; Rex C Yung, MD: Affiliations. Department of Medici... more ... Baltimore, MD 21205, USA. email address ,; Rex C Yung, MD: Affiliations. Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. ,; Paul Strickland, PhD: Affiliations. Departments of Epidemiology and ...
Most smoke-free legislation to reduce secondhand smoke (SHS) exposure exempts waterpipe (hookah) ... more Most smoke-free legislation to reduce secondhand smoke (SHS) exposure exempts waterpipe (hookah) smoking venues. Few studies have examined SHS exposure in waterpipe venues and their employees. We surveyed 276 employees of 46 waterpipe tobacco venues in Istanbul, Moscow, and Cairo. We interviewed venue managers and employees and collected biological samples from employees to measure exhaled carbon monoxide (CO), hair nicotine, saliva cotinine, urine cotinine, urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and urine 1-hydroxypyrene glucuronide (1-OHPG). We estimated adjusted geometric mean ratios (GMR) of each SHS biomarker by employee characteristics and indoor air SHS measures. There were 73 non-smoking employees and 203 current smokers of cigarettes or waterpipe. In non-smokers, the median (interquartile) range concentrations of SHS biomarkers were 1.1 (0.2, 40.9) µg/g creatinine urine cotinine, 5.5 (2, 15) ng/mL saliva cotinine, 0.95 (0.36, 5.02) ng/mg hair nicotine, 1.48 (0.98, 3.97) pg/mg creatinine urine NNAL, 0.54 (0.25, 0.97) pmol/mg creatinine urine 1-OHPG, and 1.67 (1.33, 2.33) ppm exhaled CO. An 8-hour increase in work hours was associated with higher urine cotinine (GMR: 1.68, 95% CI: 1.20, 2.37) and hair nicotine (GMR: 1.22, 95% CI: 1.05, 1.43). Lighting waterpipes was associated with higher saliva cotinine (GMR: 2.83, 95% CI: 1.05, 7.62). Non-smoking employees of waterpipe tobacco venues were exposed to high levels of SHS, including measurable levels of carcinogenic biomarkers (tobacco-specific nitrosamines and PAHs). Smoke-free regulation should be extended to waterpipe venues to protect non-smoking employees and patrons from the adverse health effects of SHS.
Journal of exposure science & environmental epidemiology, 2017
Polycyclic aromatic hydrocarbons (PAHs), the by-products of incomplete combustion of organic mate... more Polycyclic aromatic hydrocarbons (PAHs), the by-products of incomplete combustion of organic materials, are commonly found on particulate matter (PM) and have been associated with the development of asthma and asthma exacerbation in urban populations. We examined time spent in the home and outdoors as predictors of exposures to airborne PAHs and measured urinary 1-hydroxypyrene-glucuronide (1-OHPG) as internal dose of PAHs in 118 children aged 5-12 years from Baltimore, MD. During weeklong periods (Saturday-Saturday) in each of four seasons: daily activities were assessed using questionnaires, indoor air nicotine and PM concentrations were monitored, and urine specimens were collected on Tuesday (day 3) and Saturday (day 7) for measurement of 1-OHPG. Time spent in non-smoking homes was associated with significantly decreased 1-OHPG concentration in urine (β=-0.045, 95% CI (-0.076, -0.013)), and secondhand smoke (SHS) exposures modified these associations, with higher urinary 1-OHPG ...
Http Dx Doi Org 10 1080 15287390252808028, Jan 7, 2011
The association between urinary 1-hydroxypyrene glucuronide (1-OHPG) levels, as an internal measu... more The association between urinary 1-hydroxypyrene glucuronide (1-OHPG) levels, as an internal measure of polycyclic aromatic hydrocarbon (PAH) exposure, and glycophorin A (GPA) mutation frequency, as an early biologic effect indicator, was determined to establish whether genetic polymorphisms of glutathione S-transferase (GST) isoforms GSTM1 and GSTT1 play a role. Eighty-one workers including 38 employees directly involved in incinerating industry wastes were recruited from a company located in South Korea. Urinary 1-OHPG levels were measured by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11. Erythrocyte GPA variant frequency (NN or NO) was assessed in MN heterozygotes with a flow cytometric assay. The GSTM1 and GSTT1 genotypes were assessed by a multiplex polymerase chain reaction (PCR) method. Urinary 1-OHPG levels were higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs. An increase was seen in GPA variant frequency levels with increase in urinary 1-OHPG levels. When this association was evaluated by GSTM1 genotype status, the association between GPA mutation and urinary 1-OHPG levels was stronger in individuals with GSTM1 genotype. These results suggest that the association between urinary 1-OHPG and GPA mutation might be modulated by the GSTM1 genotype.
Journal of Occupational and Environmental Medicine, Oct 1, 1998
5-Aminolevulinic acid (ALA) is the first intermediate substrate in the heme synthetic pathway and... more 5-Aminolevulinic acid (ALA) is the first intermediate substrate in the heme synthetic pathway and is the substrate of aminolevulinic acid dehydratase (ALAD, porphobilinogen synthase). Because lead effectively inhibits ALAD activity, resulting in accumulation of ALA in urine and blood, urinary ALA (ALAU) has been used as a biomarker for lead exposure or early biologic effect of lead. Intraindividual variation in urinary excretion of ALA requires the use of 24-hour urine samples or adjustment of single urine samples by other normalizing variables, such as urinary creatinine concentration. Previous studies of ALAU concentration have used various adjustment methods; however, few have compared creatinine-adjusted ALAU concentration with ALA concentration in plasma (ALAP) from subjects with low (< 30 micrograms/dL) to moderate (< 60 micrograms/dL) levels of blood lead. To determine if creatinine-adjusted ALAU is associated with ALAP, we measured ALAU, ALAP, and urinary creatinine in 65 Korean lead workers with blood lead concentrations in the range of 14-60 micrograms/dL. ALAU, ALAU/creatinine, or ALAU/log creatinine all correlated with ALAP. However, ALAU/creatinine correlated more closely with ALAP based on Spearman's r (rs = 0.40, P, = 0.0009), supporting the use of ALA/creatinine in single urine samples as a surrogate for ALAP.
Cancer Epidemiology Biomarkers Prevention a Publication of the American Association For Cancer Research Cosponsored By the American Society of Preventive Oncology, Jun 1, 1999
Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis, Aug 17, 2005
Cross-sectional biomarker studies can provide a snapshot of the frequency and characteristics of ... more Cross-sectional biomarker studies can provide a snapshot of the frequency and characteristics of exposure/disease in a population at a particular point in time and, as a result, valuable insights for delineating the multi-step association between exposure and disease occurrence. Three major issues should be considered when designing biomarker studies: selection of appropriate biomarkers, the assay (laboratory validity), and the population validity of the selected biomarkers. Factors related to biomarker selection include biological relevance, specificity, sensitivity, biological half-life, stability, and so on. The assay attributes include limit of detection, reproducibility/reliability, inter-laboratory variation, specificity, time, and cost. Factors related to the population validity include the frequency or prevalence of markers, greater inter-individual variation than intra-individual variation, intra-class correlation coefficients (ICC), association with potential confounders, invasiveness of specimen collection, and subject selection. Three studies are selected to demonstrate different features of cross-sectional biomarker studies: (1) characterizing the determinants of the biomarkers (study I: urinary PAH metabolites and environmental particulate exposure), (2) relationship of multiple biomarkers of exposure and effect (study II: relationship between urinary PAH metabolites and oxidative stress), and (3) evaluating gene-environmental interaction (study III: effect of genetic polymorphisms of GSTM1 on the association of green tea consumption and urinary 1-OHPG levels in shipbuilding workers).
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