Carbon Monoxide Association Research Articles

Association of household air pollution exposure and anemia among pregnant women: Analysis of baseline data from ’Household Air Pollution Intervention Network (HAPIN)’ trial

BackgroundAnemia is common in low- and middle-income countries (LMICs), causing significant health issues and social burdens. Exposure to household air pollution from using biomass fuels for cooking and heating has been associated with anemia, but the exposure–response association has not been studied. ObjectivesWe evaluated the associations between personal exposure to air pollution and both hemoglobin levels and anemia prevalence among pregnant women in a multi-country randomized controlled trial. MethodsWe studied 3,163 pregnant women aged 18–35 years with 9–20 weeks of gestation, recruited as part of the Household Air Pollution Intervention Network (HAPIN) randomized controlled trial in Guatemala, India, Peru, and Rwanda. We assessed 24-hour personal exposures to fine particulate matter (PM2.5), black carbon (BC), and carbon monoxide (CO), and measured hemoglobin levels at baseline (15 ± 3 weeks gestation). Linear and logistic regression models were used to examine the associations of measured pollutants with hemoglobin levels and anemia prevalence, adjusting for confounding. ResultsSingle-pollutant models showed associations of CO with higher hemoglobin levels and lower anemia prevalence. Bipollutant models involving CO and PM2.5 also revealed that an interquartile range (IQR) increase in CO concentrations (2.26 ppm) was associated with higher hemoglobin levels [β = 0.04; 95 % confidence interval (CI): 0.01, 0.07], and a lower odds of anemia prevalence [odds ratios (OR) = 0.90; 95 % CI: 0.83, 0.98]. PM2.5 was inversely related to hemoglobin and positively associated with anemia, but results were not statistically significant at the 0.05 alpha level. County-specific results showed that 3 of 4 countries showed a similar association between CO and hemoglobin. We found no association of BC levels with hemoglobin levels or with anemia prevalence. ConclusionOur findings suggest that exposure to CO is associated with higher hemoglobin and lower anemia prevalence among pregnant women, whereas PM2.5 showed the opposite associations.

Associations of long-term exposure to ambient sulfur dioxide, carbon monoxide, ozone, and benzene with risk of incident chronic kidney disease in the UK

Limited studies have examined associations of gaseous air pollutants exposure with chronic kidney disease (CKD) in Europe. This study aimed to calculate the relationships between long-term exposure to ambient sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), and benzene and CKD in the UK. We included 502 369 participants from the UK biobank cohort. Associations of SO2, CO, O3, and benzene with CKD were estimated using Cox proportional hazards model. The shape of the exposure-response association between each air pollutant and CKD was then depicted using the shape constrained health impact function. We finally estimated the incidence of CKD attributable to each air pollutant by linking the constructed exposure-response association to the 2019 Global Burden of Disease data. Our results suggested SO2, high O3 days (daily max 8 hr O3 concentration > 120 µg m−3), CO, and benzene were positively associated with the risk of incident CKD. The hazard ratios (HRs) of CKD for SO2, CO, and benzene were 1.058 (95% CI: 1.039–1.078), 1.003 (95% CI: 1.001–1.005), and 1.619 (1.433–1.829) for every 1 μg m−3 increase in the concentration, respectively. For high O3 days, the HR of CKD was 1.044 (95% CI: 1.032–1.056) for every 1 d increase, but correlation to O3 concentration did not reach the statistical significance in the time-varying model. The risk of CKD increased non-linearly with increasing SO2, high O3 days, and CO, and linearly with increasing benzene. We estimated that 7.9%, 16.0%, 8.0% of incident CKD cases in the UK in 2021 could be attributed to exposure to SO2, O3, and benzene, respectively. We concluded that exposure to SO2, CO, O3, and benzene were all positively associated with increased CKD risk. Our findings highlight the importance of considering air pollution while making strategies targeting on CKD management.

Air Pollution and Influenza: A Systematic Review and Meta-Analysis.

Influenza is the first infectious disease that implements global monitoring and is one of the major public health issues in the world. Air pollutants have become an important global public health issue, in recent years, and much epidemiological and clinical evidence has shown that air pollutants are associated with respiratory diseases. We comprehensively searched articles published up to 15 November 2022 in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Database of Chinese sci-tech periodicals, and Wanfang Database. The search strategies were based on keyword combinations related to influenza and air pollutants. The air pollutants included particulate matter (PM2.5, PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3). Meta-analysis was performed using the R programming language (R4.2.1). A total of 2926 records were identified and 1220 duplicates were excluded. Finally, 19 studies were included in the meta-analysis according to inclusion and exclusion criteria. We observed a significant association between partial air pollutants (PM2.5, NO2, PM10 and SO2) and the incidence risk of influenza. The RRs were 1.0221 (95% CI: 1.0093~1.0352), 1.0395 (95% CI: 1.0131~1.0666), 1.007 (95% CI: 1.0009~1.0132), and 1.0352 (95% CI. 1.0076~1.0635), respectively. However, there was no significant relationship between CO and O3 exposure and influenza, and the RRs were 1.2272 (95% CI: 0.9253~1.6275) and 1.0045 (95% CI: 0.9930~1.0160), respectively. Exposure to PM2.5, NO2, PM10, and SO2 was significantly associated with influenza, which may be risk factors for influenza. The association of CO and O3 with influenza needs further investigation.

Association of ambient carbon monoxide exposure with hospitalization risk for respiratory diseases: A time series study in Ganzhou, China.

Ambient carbon monoxide (CO) exposure is associated with increased mortality and hospitalization risk for total respiratory diseases. However, evidence on the risk of hospitalization for specific respiratory diseases from ambient CO exposure is limited. Data on daily hospitalizations for respiratory diseases, air pollutants, and meteorological factors from January 2016 to December 2020 were collected in Ganzhou, China. A generalized additive model with the quasi-Poisson link and lag structures was used to estimate the associations between ambient CO concentration and hospitalizations of total respiratory diseases, asthma, chronic obstructive pulmonary disease (COPD), upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), and influenza-pneumonia. Possible confounding co-pollutants and effect modification by gender, age, and season were considered. A total of 72,430 hospitalized cases of respiratory diseases were recorded. Significant positive exposure-response relationships were observed between ambient CO exposure and hospitalization risk from respiratory diseases. For each 1 mg/m3 increase in CO concentration (lag0-2), hospitalizations for total respiratory diseases, asthma, COPD, LRTI, and influenza-pneumonia increased by 13.56 (95% CI: 6.76%, 20.79%), 17.74 (95% CI: 1.34%, 36.8%), 12.45 (95% CI: 2.91%, 22.87%), 41.25 (95% CI: 18.19%, 68.81%), and 13.5% (95% CI: 3.41%, 24.56%), respectively. In addition, the associations of ambient CO with hospitalizations for total respiratory diseases and influenza-pneumonia were stronger during the warm season, while women were more susceptible to ambient CO exposure-associated hospitalizations for asthma and LRTI (all P < 0.05). In brief, significant positive exposure-response relationships were found between ambient CO exposure and hospitalization risk for total respiratory diseases, asthma, COPD, LRTI, and influenza-pneumonia. Effect modification by season and gender was found in ambient CO exposure-associated respiratory hospitalizations.

Annual exposure to PM10 is related to cerebral small vessel disease in general adult population

Ambient air pollution is one of the most important global health issues. Although several studies have been reported the associations between air pollution and brain function or structure, impact of the air pollution on cerebral small vessel disease (cSVD) have rarely been explored in Asian adult population. We evaluated the association between exposure to air pollutants and cSVD in Korean asymptomatic adults. This cross-sectional study included 3257 participants of a health screening program from January 2006 to December 2013. All participants performed brain magnetic resonance imaging. To assess the cSVD, we considered three features such as white matter hyperintensities (WMH), silent lacunar infarction (SLI), and cerebral microbleeds (CMBs). The annual average exposure to air pollutants [particulate matter ≤ 10 μm in aerodynamic diameter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO)] was generated. The mean [standard deviation (SD)] age of the total 3257 participants was 56.5 (9.5) years, and 54.0% of them were male. Among all the included participants, 273 (8.4%) had SLI and 135 (4.1%) had CMBs. The mean volume (± SD) of WMH was 2.72 ± 6.57 mL. In result of linear regression analysis, the volume of WMH was associated with various potential factors including age, height, weight, smoking and alcohol consumption status, blood pressure (BP), hypertension, and diabetes mellitus. SLI-positive group, compared to the SLI-negative group, was older, shorter, and had higher BP as well as higher frequency of hypertension and diabetes mellitus. After adjusting for covariates, the annual average concentration of PM10 was significantly associated with the volume of WMH [β (95% CI) for Model 1 = 0.082 (0.038- 0.125), p < 0.001; β (95% CI) for Model 2 = 0.060 (0.013, 0.107), p = 0.013]. CMBs were not associated with the annual average concentration of PM10. No significant associations of NO2, SO2, and CO with cSVD were observed. In conclusion, PM10 exposure is associated with significant increases in brain WMH’ volume and silent lacunar infarcts in asymptomatic adults.

Calcium-Dependent Changes in Cellular Redox Homeostasis and Heat Resistance of Wheat Plantlets under Influence of Hemin (Carbon Monoxide Donor)

Carbon monoxide (CO) is considered to be an important molecule-gasotransmitter involved in the regulation of the functional activity of plants, including in the processes of adaptation to stress factors. However, the associations of CO with other participants of signaling in the plant cells remain poorly studied. Using an inhibitory method, the role of different calcium pools in realization of the influence of hemin (carbon monoxide donor) on generation and neutralization of reactive oxygen species (ROS) in the root cells of wheat (Triticum aestivum L.) plantlets and their resistance to damaging heating (45°C, 10 min) was studied. The treatment of plantlets with 5 μM hemin caused a transient increase in the activity of extracellular peroxidase in roots and an increase in the generation of ROS with the maximum in 1.5–2 h after the beginning of treatment. The chelator of extracellular calcium EGTA and the inhibitor of inositol-1,4,5-phosphate formation neomycin, which reduces calcium influx into the cytosol from intracellular compartments, almost completely eliminated an increase in the activity of extracellular peroxidase caused by exogenous CO. At the same time, EGTA (completely) and neomycin (partially) leveled an increase in the content of hydrogen peroxide in the roots of plantlets occurring under the influence of CO donor. The treatment of plantlets with hemin also induced an increase in the activity of superoxide dismutase, catalase, and intracellular peroxidase in roots. Both calcium antagonists eliminated these effects. In the presence of EGTA and neomycin, there was also no positive effect of the treatment of hemin on the state of biomembranes and survival of plantlets after the damaging heating. It was concluded that both extracellular calcium and that deposited in intracellular compartments is involved in CO donor-induced increase in the formation of ROS, induction of the antioxidant system, and development of heat resistance of wheat plantlets.

Examining the relationship between ambient carbon monoxide, nitrogen dioxide, and mental health-related emergency department visits in California, USA

Growing evidence suggests air pollutants may harm the central nervous system, potentially impacting mental health. However, such impacts of air pollutants on mental health and the sub-populations most affected remain poorly understood, especially in California. We examined the relationship between short-term ambient carbon monoxide (CO), nitrogen dioxide (NO2), and mental health-related emergency department (ED) visits in California from 2005 to 2013. Daily mean concentrations of the pollutants were acquired from the U.S. Environmental Protection Agency Air Quality System Data Mart ground monitoring data. Moving averages of pollutant concentrations were linked to counts of ED visits obtained from the California Office of Statewide Health Planning and Development. Seven mental health outcomes, defined by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, were studied: all mental disorders, bipolar disorder, depression, schizophrenia, substance abuse, homicide/inflicted injury, and suicide/self-harm. Monitor-level associations were estimated with quasi-Poisson regression models and combined using random-effects meta-analysis. CO and NO2 were found to be positively associated with ED visits due to homicide/inflicted injury, with the warm season (May–October) driving the CO association. An interquartile range (IQR) (0.28 ppm) increase in two-day average CO during the warm season was associated with a 3.13% (95% confidence interval (CI): 1.43, 4.84) elevation in risk of an ED visit due to homicide/inflicted injury (n = 122,749 ED visits). An IQR (10.79 ppb) increase in two-day average NO2 was associated with a 2.60% (95% CI: 1.17, 4.05) elevation in risk of an ED visit due to homicide/inflicted injury (n = 206,919 ED visits). Subgroup analyses indicated children, Hispanics, and males were particularly vulnerable. Except for an inverse relationship between NO2 and substance abuse, neither pollutant was robustly associated with visits due to other mental health morbidities. Our results suggest short-term elevations in CO and NO2 may promote violent behavior. Further investigation in other populations and ranges of air pollution exposure is warranted.

Unexpected association between increased levels of ambient carbon monoxide and reduced daily outpatient visits for vaginitis: A hospital-based study

Carbon monoxide (CO) is a well-known “toxic gas”. It represents a toxic inhalation hazard at high concentration and is commonly found in polluted air. However, a series of recent studies have suggested that low concentration of CO can also produce protective functions. This study was performed to investigate the association between ambient CO exposure and vaginitis outpatient visits. Daily baseline outpatient data of vaginitis from January 1, 2013 to December 31, 2015 were obtained from Xi'an, a heavily-polluted metropolis in China. The over-dispersed Poisson generalized additive model was applied to discover the relations between short-term ambient CO exposure and the number of vaginitis outpatient visits by adjusting day of the week and weather conditions. A total of 16,825 outpatient hospital visits for vaginitis were recorded. The mean daily concentration of carbon monoxide (CO) was well below Chinese and WHO guidelines. During the study period, increased levels of ambient CO was associated with reduced outpatient-visits through concurrent to lag 5 days, and the most significant association was evidenced at lag 05. A 0.1 mg/m3 increase in daily average CO at lag 05 corresponded to −1.25% (95%CI: −1.85%, −0.65%) change in outpatient-visits for vaginitis. Moreover, the association was more significant in those women aged 20–29 years. After adjustment for PM10, PM2.5, SO2, and NO2, and O3, the negative associations of CO with vaginitis kept significant, suggesting relative stability of effect estimates. In summary, this is the first evidence that increased ambient CO exposure can be related to reduced daily outpatient visits for vaginitis. The results of our study may not only help to establish more comprehensive understanding of the health effects of ambient air on vaginitis and other gynecological diseases, but also provide a clue to new potential interventions.

Relationship between long-range transported atmospheric black carbon and carbon monoxide at a high-altitude background station in East Asia

Lulin Atmospheric Background Station (LABS, 23.47°N, 120.87°E; 2862 m above sea level) at the summit of Mount Lulin in central Taiwan was established in spring 2006 and is the only high-altitude background station over western Pacific region in East Asia to study the impact of various air pollutants through long-range transport. Continuous in-situ measurements of equivalent black carbon (EBC) and carbon monoxide (CO) concentrations were made at LABS from June 2012 to May 2014 and their association was investigated in this study. The highest monthly concentration of EBC (median; 840 ng m−3) and CO (212 ppbv) in March were primarily attributed to the westerly winds coupled with biomass-burning (BB) emissions from Southeast Asia (SEA) region. The association of EBC and CO was weak at LABS possibly due to the influence of dissimilar air masses from various sources, and scavenging or dilution of EBC during the long-range atmospheric transport to Mt. Lulin. The mean ΔEBC/ΔCO ratio (slope of least-squares regression line of ΔEBC-ΔCO scatterplot; where Δ indicates surplus amounts with respect to the background value) was found the most significant in March (5.3 ng m−3 ppbv−1 or 7.3 × 10−3 g of carbon as EBC per gram of carbon as CO). On the basis of episodic cases, the mean ΔEBC/ΔCO ratios at LABS were estimated to be 6.1, 8.0, and 2.4 ng m−3 ppbv−1 for SEA BB emissions, southern China mixed pollution, and northern China mixed pollution, respectively. A total of 32% loss in EBC aerosols (6.4% of EBC removal per day) was estimated for the atmospheric transport of BB emissions from SEA region to LABS. This study provides needful information to understand the ΔEBC/ΔCO ratios at a remote site and would be used in model simulations to evaluate BC aging and scavenging over western Pacific region in East Asia.

Epidemiologic Characteristics of Carbon Monoxide Poisoning: Emergency Department Based Injury In-depth Surveillance of Twenty Hospitals

Purpose: This study was conducted to describe the characteristics of patients with carbon monoxide (CO) poisoning. Methods: We retrospectively surveyed data from the Emergency Department based Injury In-depth Surveillance of 20 hospitals (2011-2014). We included patients whose mechanism of injury was acute CO poisoning caused by inhalation of gases from charcoal or briquettes. We surveyed the annual frequency, gender, age, result of emergency treatment, rate of intensive care unit (ICU) admission, result of admission, association with alcohol, and place of accident. We also surveyed the cause and experience of past suicide attempts by intentional poisoning. Results: A total of 3,405 patients were included (2,015 (59.2%) and 1,390 (40.8%) males and females, respectively) with a mean age of $39.83{pm}18.51$ year old. The results revealed that the annual frequency of CO poisoning had increased and the frequency of unintentional CO poisoning was higher than that of intentional CO poisoning in January, February and December. The mean age of intentional CO poisoning was younger than that of unintentional CO poisoning ($38.41{pm}13.03$ vs $40.95{pm}21.83$) (p&lt;0.001). The rates of discharge against medical advice (DAMA), ICU care and alcohol association for intentional CO poisoning were higher than for unintentional CO poisoning (36.4% vs 14.0%, 17.8% vs 4.7%, 45.2% vs 5.6%) (p&lt;0.001). The most common place of CO poisoning was in one's residence. Conclusion: The annual frequency of total CO poisoning has increased, and unintentional CO poisoning showed seasonal variation. DAMA, ICU care, and alcohol association of intentional CO poisoning were higher than those of unintentional CO poisoning.

Carbon monoxide and stroke: A time series study of ambient air pollution and emergency hospitalizations

BackgroundRecent experimental and clinical studies suggested that exogenous carbon monoxide (CO) at low concentrations may have beneficial neuroprotective effects under certain circumstances. However, population-based epidemiological studies of environmentally relevant CO exposure generated mixed findings. The present study aimed to examine the short-term association of ambient CO with emergency stroke hospitalizations. MethodsA time series study was conducted. Daily air pollution concentrations and emergency hospital admission data from January 2004 to December 2011 in Hong Kong were collected. Generalized additive Poisson models were used to estimate the associations between daily 24-hour mean concentrations of CO and emergency hospital admissions for stroke, while controlling for other traffic related co-pollutants: NO2 and PM2.5. Sensitivity analyses were performed using daily 1-hour maximum concentration of CO as exposure indicator. ResultsNegative associations were observed between ambient CO concentrations and emergency hospital admissions for stroke. The previous 1–3day cumulative exposure to CO was associated with a −2.0% (95%CI, −3.3% to −0.7%) decrease in stroke admissions per interquartile range (IQR) increment in CO concentration (0.3ppm). Similar results were obtained when using 1-hour maximum concentration of CO as exposure indicator. The negative association was robust to the co-pollutant adjustment for either NO2 or PM2.5. Females and elders appeared to be more sensitive to ambient CO exposure. The negative association tended to be larger in cool season. ConclusionShort-term exposure to ambient CO was associated with decreased risk of emergency hospitalizations for stroke, suggesting some acute protective effects of CO exposure against stroke onsets.

Black carbon and carbon monoxide over Bay of Bengal during W_ICARB: Source characteristics

The ship borne measurements of near-surface black carbon (BC) and carbon monoxide (CO) were carried out over Bay of Bengal (BoB) during the winter period of 2009 under W_ICARB, the second phase of ‘Integrated Campaign for Aerosols, gases and Radiation Budget (ICARB)’. The CO mixing ratio and BC mass concentration varied in the ranges of 80–480 ppbv and 75–10,000 ng m−3, respectively over this marine region. The BC and CO showed similar variations over northern BoB where airmass from Indo-Gangetic Plain (IGP) region prevailed during the observations period leading to a very strong positive correlation. The association of BC and CO was poor over the eastern and southern part of BoB could be due to the removal of BC aerosols by rain and/or processes of dilution and mixing while transported over to BoB. The highest value of CO observed over eastern BoB was partially due to biomass burning over East Asia. The BC/CO ratio for IGP airmass found to be 20.3 ng m−3 ppb−1 and ∼16 ng m−3 ppb−1 during winter and pre-monsoon, respectively which indicate the role of biomass burning as the source of BC over the region. Based on the emission flux of CO from various inventories and observed BC/CO ratios during pre-monsoon and winter, the BC emission for India is estimated to be in the range of 0.78–1.23 Tg year−1. The analysis of scavenging of BC revealed the loss rate of BC due to relative humidity 0.39 ± 0.08 ng m−3 ppb−1 RH (%)−1 over northern BoB and 0.53 ± 0.04 ng m−3 ppb−1 RH (%)−1 over the southern-BoB during winter.

Azurin–DNA Conjugate with the Binding Motif of a Transcriptional Regulator, CooA: CO-dependent Modulation of the Electron-transfer Reaction

Abstract An azurin–DNA conjugate (Azu–DNA) where the DNA part contains the binding sequence of a carbon monoxide (CO)-dependent transcriptional regulator, CooA, has been prepared. CooA in the CO-bound form (CO–CooA) showed specific binding to Azu–DNA. The association of CO–CooA with Azu–DNA affects the electron transfer (ET) between Azu–DNA and its redox partner protein, cytochrome c552. Consequently, the CO-dependent modulation of ET was achieved. This could be a potential platform for a novel biobased sensor, which exploits the transcriptional regulator as a detection module and whose readout is immediately transduced to a readily processable electronic signal.

Ambient carbon monoxide and daily mortality in three Chinese cities: The China Air Pollution and Health Effects Study (CAPES)

Ambient carbon monoxide (CO) is an air pollutant primarily generated by traffic. CO has been associated with increased mortality and morbidity in developed countries, but few studies have been conducted in Asian developing countries. In the China Air Pollution and Health Effects Study (CAPES), the short-term associations between ambient CO and daily mortality were examined in three Chinese cities: Shanghai, Anshan and Taiyuan. Poisson regression models incorporating natural spline smoothing functions were used to adjust for long-term and seasonal trend of mortality, as well as other time-varying covariates. Effect estimates were obtained for each city and then for the cities combined. In both individual-city and combined analysis, significant associations of CO with both total non-accidental and cardiovascular mortality were observed. In the combined analysis, a 1 mg/m 3 increase of 2-day moving average concentrations of CO corresponded to 2.89% (95%CI: 1.68, 4.11) and 4.17% (95%CI: 2.66, 5.68) increase of total and cardiovascular mortality, respectively. CO was not significantly associated with respiratory mortality. Sensitivity analyses showed that our findings were generally insensitive to alternative model specifications. In conclusion, ambient CO was associated with increased risk of daily mortality in these three cities. Our findings suggest that the role of exposure to CO and other traffic-related air pollutants should be further investigated in China.

Dynamics of Carbon Monoxide Binding to Cystathionine β-Synthase

Cystathionine beta-synthase (CBS) condenses homocysteine, a toxic metabolite, with serine in a pyridoxal phosphate-dependent reaction. It also contains a heme cofactor to which carbon monoxide (CO) or nitric oxide can bind, resulting in enzyme inhibition. To understand the mechanism of this regulation, we have investigated the equilibria and kinetics of CO binding to the highly active catalytic core of CBS, which is dimeric. CBS exhibits strong anticooperativity in CO binding with successive association constants of 0.24 and 0.02 microm(-1). Stopped flow measurements reveal slow CO association (0.0166 s(-1)) limited by dissociation of the endogenous ligand, Cys-52. Rebinding of CO and of Cys-52 following CO photodissociation were independently monitored via time-resolved resonance Raman spectroscopy. The Cys-52 rebinding rate, 4000 s(-1), is essentially unchanged between pH 7.6 and 10.5, indicating that the pK(a) of Cys-52 is shifted below pH 7.6. This effect is attributed to the nearby Arg-266 residue, which is proposed to form a salt bridge with the dissociated Cys-52, thereby inhibiting its protonation and slowing rebinding to the Fe. This salt bridge suggests a pathway for enzyme inactivation upon CO binding, because Arg-266 is located on a helix that connects the heme and pyridoxal phosphate cofactor domains.

The Position 68(E11) Side Chain in Myoglobin Regulates Ligand Capture, Bond Formation with Heme Iron, and Internal Movement into the Xenon Cavities

After photodissociation, ligand rebinding to myoglobin exhibits complex kinetic patterns associated with multiple first-order geminate recombination processes occurring within the protein and a simpler bimolecular phase representing second-order ligand rebinding from the solvent. A smooth transition from cryogenic-like to solution phase properties can be obtained by using a combination of sol-gel encapsulation, addition of glycerol as a bathing medium, and temperature tuning (-15 --> 65 degrees C). This approach was applied to a series of double mutants, myoglobin CO (H64L/V68X, where X = Ala, Val, Leu, Asn, and Phe), which were designed to examine the contributions of the position 68(E11) side chain to the appearance and disappearance of internal rebinding phases in the absence of steric and polar interactions with the distal histidine. Based on the effects of viscosity, temperature, and the stereochemistry of the E11 side chain, the three major phases, B --> A, C --> A, and D --> A, can be assigned, respectively, to ligand rebinding from the following: (i) the distal heme pocket, (ii) the xenon cavities prior to large amplitude side chain conformational relaxation, and (iii) the xenon cavities after significant conformational relaxation of the position 68(E11) side chain. The relative amplitudes of the B --> A and C --> A phases depend markedly on the size and shape of the E11 side chain, which regulates sterically both ligand return to the heme iron atom and ligand migration to the xenon cavities. The internal xenon cavities provide a transient docking site that allows side chain relaxations and the entry of water into the vacated distal pocket, which in turn slows ligand recombination markedly.

Winter air pollution and disease parameters in advanced chronic obstructive pulmonary disease panels residing in Denver, Colorado

Ambient pollution might worsen chronic obstructive pulmonary disease (COPD). We explored the associations of pollution to pulmonary function, rescue medication, and symptoms over 2 winters in 2 panels of subjects with advanced COPD in Denver, Colorado. Subjects measured lung function and recorded symptoms and rescue medications. Daily ambient pollution concentrations for particulate matter (PM(10) and PM(2.5)), carbon monoxide (CO), and nitrogen dioxide (NO(2)) were obtained for Denver. Estimated effects of pollution on outcomes were derived for the same day and 1 and 2 days after pollution measurements (lags 0, 1, and 2, respectively). Sixteen (mean age, 65.8 years; mean FEV 1 , 42.3% of predicted value) and 18 (mean age, 67.4 years; mean FEV 1 , 39.4% of predicted value) subjects participated in the first and second winters, respectively. There were no differences in demographic or disease characteristics between the 2 panels. In the first winter no detrimental associations were found. In the second winter, however, there were significant detrimental associations of CO in the morning and PM(10), CO, and NO(2) in the evening, increasing medication use at lag 0. Total symptom score increased at lag 0 with NO(2). The concentrations of particulates were increased in the second winter compared with in the first winter, and this winter was colder and more humid. In the second winter, subjects with severe COPD had worse lung function at lags 0 and 1 and increased rescue medication at lag 0 with increases in ambient air pollution. The effects of pollution varied between the 2 winters, perhaps related to levels of pollution and weather patterns. Significant effects were seen despite ambient pollution levels that conformed to US Environmental Protection Agency standards.

Structure and ligand binding properties of leucine 29(B10) mutants of human myoglobin.

Site-specific mutants of human myoglobin (Mb) have been prepared, in which Leu29 (B10) is replaced by Ala(L29A) or Ile(L29I), in order to examine the influence of this highly conserved residue in the hydrophobic clusters of the heme distal site on the heme environmental structure and ligand binding properties of Mb. Structural characterizations of these recombinant Mbs are studied by electronic absorption, infrared (IR), one- and two-dimensional proton nuclear magnetic resonance spectroscopies, and ligand-binding kinetics by laser photolysis measurements under ambient and high pressures (up to 2000 bar). Multiple split carbon monoxide (CO) stretch bands in the IR spectra of mutant Mbs exhibit a relative decrease of the 1945 cm-1 band (approximately 50%) which is associated with an upright binding geometry of CO, accompanied by an increase of the tilted CO conformer at 1932 cm-1. On the basis of these results, replacement of Leu29(B10) by Ala or Ile appears to allow bound CO to rotate from a conformation pointing toward the beta meso carbon of the heme group to the one pointing toward the alpha meso carbon atom, presumably filling the space left by removal of the delta 2 carbon atom of Leu29(B10). These substitutions cause the rate constants for CO and O2 association to decrease almost 3-5-fold. Present results show that CO and O2 bindings to the heme iron of Mb are controlled by Leu29(B10) by influencing the structure of close vicinity of the heme and the geometry of iron-bound ligand. Further, mutant Mbs (Leu72(E15)----Ala and Leu104 (G5)----Ala) which have altered residues in another hydrophobic clusters around proximal and distal site are also examined.

Effect of the distal histidine modification (cyanation) of myoglobin on the ligand binding kinetics and the heme environmental structures

The kinetics of carbon monoxide (CO) binding to myoglobin (Mb) modified at the distal histidine (His) by cyanogen bromide (BrCN) has been studied. The CO association and dissociation rates of BrCN-modified Mb were obtained as 1.8 x 10(3) M-1 s-1 and 0.13 s-1, respectively (20 degrees C and pH 7.0). Thermodynamic parameters were obtained as well. These values are notable, compared with those for other hemoproteins, the slowest association and the fastest dissociation rates among various hemoproteins examined so far. On the basis of the available structural data obtained from the absorption, 1H NMR, and IR spectral measurements, these unique kinetic and thermodynamic properties were reasonably explained in terms of the steric restriction at the modified distal side.

Discrimination between Oxygen and Carbon Monoxide and Inhibition of Autooxidation by Myoglobin: Site-directed mutagenesis of the distal histidine

Sperm whale myoglobin mutants were constructed using site-directed mutagenesis to replace the highly conserved distal histidine residue (His(E7)-64). His-64 was substituted with Gly, Val, Phe, Cys, Met, Lys, Arg, Asp, Thr, and Tyr, and all 10 mutant proteins expressed to approximately 10% of the total soluble cell protein in Escherichia coli as heme containing myoglobin. With the exception of His-64→Tyr, which did not form a stable oxygen (O2) complex, all mutant proteins could be reduced and bound O2 and carbon monoxide (CO) reversibly. However, removal of the distal histidine increased the rate of autooxidation 40–350-fold. The His-64→Gly, Val, Phe, Met, and Arg mutants all showed markedly increased O2 dissociation rate constants which were ∼50–1500-fold higher than those for wild-type myoglobin and increased O2 association rate constants which were ∼5–15-fold higher than those for the native protein. All mutants studied (except His-64→Tyr) showed ∼10-fold increased CO association rates and relatively unchanged CO dissociation rates. These altered O2 and CO association and dissociation rate constants resulted in 3–14-fold increased CO affinities, 10–200-fold decreased O2 affinities, and 50–380-fold greater M (KCO/KO2) values for the mutants compared to the wild-type protein. Thus, the distal histidine of myoglobin discriminates between CO and O2 binding by both sterically hindering bound CO and stabilizing bound O2 through hydrogen bonding. The increased autooxidation rates observed for the mutants appear to be due to a decrease in oxygen affinity and an increase in solvent anion accessibility to the distal pocket.