Perceptions of causal attribution and attitudes to genetic testing among people with schizophrenia and their first-degree relatives.

Rapid advances in the genetics of psychiatric disorders mean that diagnostic and predictive genetic testing for schizophrenia risk may one day be a reality. This study examined how causal attributions for schizophrenia contribute to interest in a hypothetical genetic test. People with schizophrenia and first-degree relatives of people with schizophrenia were recruited through a schizophrenia research bank and mental health organisation. Semi-structured telephone interviews were conducted with 13 individuals with schizophrenia and 8 first-degree relatives. Transcripts were subjected to a qualitative analysis using the thematic analysis framework. Five themes were developed: (i) "It is like a cocktail", with most participants aware that both genetic and environmental factors contributed to causation, and many mentioning the positive impact of genetic causal explanations; (ii) "Knowledge is power" (i.e., in favour of genetic testing); (iii) Genetic testing provides opportunities for early intervention and avoiding triggers, with participants citing a wide range of perceived benefits of genetic testing but few risks; (iv) Views on reproductive genetic testing for schizophrenia risk with a few participants viewing it as "playing God" but not necessarily being against it; and (v) "It snowballs", whereby participants' understanding of genetics was sophisticated with most believing that multiple rather than single genes contributed to schizophrenia. In conclusion, many individuals had a sound understanding of the role of genetic testing if it were to become available, with evidence of insight into the role of multiple genes and the contribution of other risk factors that may interact with any inherited genetic risk.

Isolation and characterization of human antibodies targeting human aspartyl (asparaginyl) beta-hydroxylase.

Over-expression of the enzyme human aspartyl (asparaginyl) beta-hydroxylase (HAAH) has been detected in a variety of cancers. It is proposed that upon cellular transformation, HAAH is overexpressed and translocated to the tumor cell surface, rendering it a specific surface antigen for tumor cells. In this work, twelve human single-chain Fv fragments (scFv) against HAAH were isolated from a human non-immune scFv library displayed on the surface of yeast. Five of the twelve were reformatted as human IgG1. Two of the five IgGs, 6-22 and 6-23, showed significant binding to recombinant HAAH in ELISA, tumor cell lines, and tumor tissues. The apparent dissociation constants of 6-22 and 6-23 IgG were 1.0 +/- 0.2 nM and 20 +/- 10 nM respectively. These two antibodies were shown to target different domains of HAAH, with 6-22 targeting the catalytic domain of HAAH and 6-23 targeting the N-terminal non-catalytic domain of HAAH. 6-22 IgG was further characterized, as it had high affinity and targeted the catalytic domain. 6-22 IgG alone does not exhibit significant cytotoxicity toward the tumor cells. However, 6-22 internalizes into tumor cells and can therefore be employed to deliver cytotoxic moieties. A goat anti-human IgG-saporin conjugate was delivered into tumor cells by 6-22 IgG and hence elicited cytotoxicity toward the tumor cells in vitro. These tumor-binding human antibodies can potentially be used in both diagnosis and immunotherapy targeting HAAH-expressing tumor cells.

Interaction between ozone and airborne particulate matter in office air.

UNLABELLED: This study investigated the hypotheses that humans are affected by air pollution caused by ozone and house dust, that the effect of simultaneous exposure to ozone and dust in the air is larger than the effect of these two pollutants individually, and that the effects can be measured as release of cytokines and changes of the respiratory function. Experimental exposures of eight atopic but otherwise healthy subjects were performed in a climate chamber under controlled conditions. The three controlled exposures were about 75 microg/m3 total suspended particulate matter, 0.3 p.p.m. ozone, and the combination of these. The exposure duration was 3 h. The outcome measures were interleukins and cells in nasal lavages (NAL), respiratory function, bronchial metacholine responsiveness, rhinometry symptoms and general well-being in a questionnaire and time course of general irritation on a visual analogue scale. Indications of interactions between exposure types were demonstrated for peak expiratory flow (PEF) (P<0.05) and for discomfort symptoms (P<0.03). Non-significant interactions were found for the concentration of interleukin-8 in NAL. The combined exposure was found to cause significantly more effects than either ozone exposures or dust exposures. This is interpreted as indications of a potentiation caused by the combined exposures to dust and ozone. The findings in this study are based on a limited number of subjects and thus should not be over-interpreted. However, they support the hypothesis that ozone at relatively high concentrations interacts with dust exposures to cause decrements in PEF and increase in discomfort measures. PRACTICAL IMPLICATIONS: If confirmed at lower ozone and dust concentrations this finding could help to explain many problems with indoor air quality reported in offices throughout the world.

Poison Control Center--based syndromic surveillance for foodborne illness.

OBJECTIVES: This retrospective study evaluated the usefulness of a poison control center (PCC) data collection system in Tucson, Arizona for early detection of foodborne disease outbreaks. METHODS: A search of a PCC database identified callers with gastrointestinal symptoms attributable to suspected foodborne illnesses whose calls were received during January 1-March 31, 2000. For each foodborne illness-related call, PCC coding was compared with a predefined diarrhea/gastroenteritis syndrome. PCC calls also were evaluated by using ZIP code, age, sex, and date of symptom onset to determine if call classifications matched any laboratory-confirmed cases reported to a county health department. RESULTS: An independent review generally agreed with the PCC's classification of calls. When calls and cases were compared, only one potential match was identified. CONCLUSION: Although confirmatory diagnostic information was not available, PCC calls were not duplicative of cases evaluated by the county health department, which suggests that they represent two independent data sets. PCC data might provide a useful addition to surveillance data reported to public health agencies for the early detection of foodborne disease outbreaks. These results will now be used to develop collaborative prospective surveillance systems.

Exposure apportionment: ranking food items by their contribution to dietary exposure.

This paper identifies and ranks food items by estimating their contribution to the dietary exposure of the US population and 19 subpopulation groups. Contributions to dietary exposures to arsenic, cadmium, chromium, lead, nickel, benzene, chlorpyrifos, and diazinon are estimated using either the Dietary Exposure Potential Model (DEPM) approach, the National Human Exposure Assessment Survey Arizona (NHEXAS-AZ) approach or the combination of the two. The DEPM is a computer model that uses several national databases of food consumption and residue concentrations for estimating dietary. The DEPM approach ranks the contribution of food items to the total dietary exposure using two methods, the direct method that ranks contributions by population exposure magnitude and the weighted method that ranks by subpopulation exposure magnitude. The DEPM approach identifies highly exposed subpopulations and a relatively small number of food items contributing the most to dietary exposure. The NHEXAS-AZ approach uses the NHEXAS-AZ database containing food consumption data for each subject and chemical residues of a composite of food items consumed by each subject in 1 day during the sampling week. These data are then modeled to obtain estimates of dietary exposure to chemical residues. The third approach uses the NHEXAS-AZ consumption data with residue values from the national residue database. This approach also estimates percent contributions to exposure of each ranked food item for the Arizona population. Dietary exposures estimated using the three approaches are compared. The DEPM results indicate groups with highest dietary exposures include Nonnursing Infants, Children 1-6, Hispanic, Non-Hispanic White, Western, Northeast and Poverty 0-130%. The use of the Combined National Residue Database (CNRD) identifies 43 food items as primary contributors to total dietary exposure; they contribute a minimum of 68% of the total dietary exposure to each of the eight chemical residues. The percent contribution of ranked food items estimated using the NHEXAS samples is smaller than those obtained from the western US population via the DEPM. This indicates differences in consumption characteristics of the two groups with respect to the ranked food items. Six of 15 food items consumed by the NHEXAS-AZ subjects per day are ranked food items contributing between 56% and 70% of the estimated NHEXAS-AZ dietary exposure to each of the eight chemical residues. The difference between total dietary exposure estimates from the DEPM and NHEXAS-AZ approaches varies by chemical residue and is attributable to differences in sampling and analytical methods, and geographic areas represented by the data. Most metal exposures estimated using the NHEXAS consumption data with the CNRD have lower values than those estimated via the other approaches, possibly because the NHEXAS-AZ residue values are higher than the CNRD values. In addition, exposure estimates are seemingly affected by the difference in demographic characteristics and factors that affect types and amounts of food consumed. Efficient control strategies for reducing dietary exposure to chemical residues may be designed by focusing on the relatively small number of food items having similar ingredients that contribute substantively to the total ingestion exposure.

Correlates of peak expiratory flow lability in elderly persons.

OBJECTIVE: To determine the correlates of the lability of peak expiratory flow (PEF) in the elderly. METHODS: A community sample of 4,581 persons > or = 65 years old from the Cardiovascular Health Study completed an asthma questionnaire and underwent spirometry. During a follow-up examination of the cohort, 1,836 persons agreed to measure PEF at home twice daily for 2 weeks, and 90% successfully obtained at least 4 days of valid measurements. PEF lability was calculated as the highest daily (PEF maximum - PEF minimum)/mean PEF. RESULTS: Mean PEF measured at home was accurate when compared to PEF determined by spirometry in the clinic. Mean PEF lability was 18% in those with current asthma (n = 165) vs 12% in healthy nonsmokers (upper limit of normal, 29%). Approximately 26% of those with asthma and 14% of the other participants had abnormally high PEF lability (> 29%). After excluding participants with asthma, other independent predictors of high PEF lability included black race, current and former smoking, airway obstruction on spirometry, daytime sleepiness, recent wheezing, chronic cough, emphysema, and wheezing from lying in a supine position. Despite having a lower mean PEF, those reporting congestive heart failure (n = 82) did not have significantly higher PEF lability. CONCLUSIONS: Measurement of PEF lability at home is highly successful in elderly persons. PEF lability > or = 30% is abnormal in the elderly and is associated with asthma.

Familial correlation in the decline of forced expiratory volume in one second.

Studies have shown evidence of significant parent-offspring and sibling correlation in FEV1, but familial aggregation of decline of FEV1 over time has not been reported. Our study population comprised 392 families enrolled in the Tucson Epidemiological Study of Airway Obstructive Diseases. Subjects were older than 18 yr of age and performed at least 3 pulmonary function tests over 5 to 20 yr. The slope of FEV1 was calculated for each subject using simple linear regression. Multiple regression models were used to compute standardized residual slope values adjusted for possible confounders. Familial correlation analysis on residual slope values demonstrated no evidence of spousal or parent-offspring correlation. However, sibling pairs were highly correlated (r = 0.256, p < 0.001, n = 166), especially smoking-concordant pairs (r = 0.483, p < 0.01 for ever-smokers, and r = 0.280, p < 0.05 for never-smokers). The residual slopes of smoking-discordant siblings were not significantly correlated (r = 0.031, p < 0.77). Genetic susceptibility to an accelerated rate of decline associated with smoking may be evidenced in the increased correlation among smoking sibling pairs, and in the lack of correlation among smoking-discordant sibling pairs. High sibling correlation in the absence of parent-offspring correlation is compatible with a recessive model of inheritance.

On predicting multi-route and multimedia residential exposure to chlorpyrifos and diazinon.

This paper formulates regression models and examines their ability to associate exposures to chlorpyrifos and diazinon in residences with information obtained from questionnaires and environmental sampling of the National Human Exposure Assessment Survey Arizona (NHEXAS-AZ) database. A knowledge-based list of 29 potential exposure determinants was assembled from information obtained from six questionnaires administered in the course of the study. This list was used to select the independent variables of each model statistically and electronically. Depending on the data type of dependent and independent variables, four classes of regression models were developed to determine desired associations. Route-specific exposures were estimated using the indirect method of exposure estimation and measurements from the NHEXAS-AZ field study. The stepwise procedure was used to construct regression models. Significance level at P=0.10 was used for entry and retention of independent variables in a model. Twelve significant regression models were formulated to quantify associations among exposures and other variables in the NHEXAS-AZ database. Route-specific exposures to pesticides associate significantly with questionnaire-based variables such as preparation of pesticides, use of pesticide inside the house, and income level; and with concentration variables in three media: dermal wipe, sill wipe, and indoor air. Models formulated in this study may be used to estimate exposures to each of the pesticides. Yet, the use of these models must incorporate clear statements of the assumptions made in the formulation as well as the coefficient of determination and the confidence and prediction intervals of the dependent variable.

Building community capacity in public health: the role of action-oriented partnerships.

Public health practice increasingly is concerned with the capacity and performance of communities to identify, implement, strengthen, and sustain collective efforts to improve health. The authors developed ways to assist local Turning Point partnerships to improve their community public health system as a secondary outcome of their work on the expressed needs of the community. Using focus groups, meeting minutes, attendance records, and meeting observation, the authors fed information back to the partnerships on systems change. A public health systems improvement plan supportive of local partnerships' work on specific health issues was funded and the collaborative research agenda was further refined.

Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study.

CONTEXT: Sleep-disordered breathing (SDB) and sleep apnea have been linked to hypertension in previous studies, but most of these studies used surrogate information to define SDB (eg, snoring) and were based on small clinic populations, or both. OBJECTIVE: To assess the association between SDB and hypertension in a large cohort of middle-aged and older persons. DESIGN AND SETTING: Cross-sectional analyses of participants in the Sleep Heart Health Study, a community-based multicenter study conducted between November 1995 and January 1998. PARTICIPANTS: A total of 6132 subjects recruited from ongoing population-based studies (aged > or = 40 years; 52.8% female). MAIN OUTCOME MEASURES: Apnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with apnea defined as a cessation of airflow and hypopnea defined as a > or = 30% reduction in airflow or thoracoabdominal excursion both of which are accompanied by a > or = 4% drop in oxyhemoglobin saturation) [corrected], obtained by unattended home polysomnography. Other measures include arousal index; percentage of sleep time below 90% oxygen saturation; history of snoring; and presence of hypertension, defined as resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication. RESULTS: Mean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing SDB measures, although some of this association was explained by body mass index (BMI). After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension, comparing the highest category of AHI (> or = 30 per hour) with the lowest category (< 1.5 per hour), was 1.37 (95% confidence interval [CI], 1.03-1.83; P for trend = .005). The corresponding estimate comparing the highest and lowest categories of percentage of sleep time below 90% oxygen saturation (> or = 12% vs < 0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension with either measure of SDB were seen in both sexes, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant associations were observed for the arousal index or self-reported history of habitual snoring. CONCLUSION: Our findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.

Predictors of longitudinal change in diffusing capacity over 8 years.

Low single-breath diffusing capacity (DL(CO)) values are associated with anatomic emphysema, but the predictors of longitudinal change in DL(CO) over many years are unknown. Study subjects were adult participants in the longitudinal Tucson Epidemiology Study of Obstructive Lung Disease who had at least one DL(CO) measurement during either of two surveys 8 yr apart (n = 543). Smoking status was determined at each examination (current, former, or never smoker). Quitters were defined as those currently smoking at the baseline DL(CO) examination (1982-1983) and self-reported as no longer smoking at the follow-up exam (1990-1991). The longitudinal DL(CO) data were analyzed using repeated measures analysis; because of missing observations this was done using a saturated random effects model. The results showed that males had higher levels of DL(CO) than females, current smokers had significantly lower levels of DL(CO) than never smokers, but there was no difference in their mean slopes over time. Smoking history, assessed using pack-years of smoking, was associated with reduced DL(CO) levels, independent of whether current or ex-smokers. Males and females demonstrated equivalent rates of decline in DL(CO) that accelerated with increasing age, and mean DL(CO) declines were associated with declines in FEV(1) between surveys.

The National Human Exposure Assessment Survey (NHEXAS) study in Arizona--introduction and preliminary results.

The objective of the National Human Exposure Assessment Survey (NHEXAS) in Arizona is to determine the multimedia distribution of total human exposure to environmental pollutants in the classes of metals, pesticides, and volatile organic compounds (VOCs) for the population of Arizona. This was accomplished by studying a probability-based sample of the total population in Arizona with a nested design for the different stages of sampling (954 Stage I, 505 Stage II, and 179 Stage III participants). This report compares the study population demographics with those from the U.S. Census and provides preliminary data on the distributions of the example pollutant for each class, lead for metals, chlorpyrifos for pesticides, and benzene for metals. The probability-based sample age and gender demographics compare reasonably well with the Census data (1990 Census and 1996 Census Estimate). The race/ethnicity compared less well with 21% Hispanics in the 1996 Census Estimate and 42% Hispanics in the entire NHEXAS-Arizona sample and 30% Hispanics as Stage III participants for this study. The chemical analyses of the various media (yard soil, foundation soil, house dust, indoor air, outdoor air, drinking water, food, and beverage) show generally low levels of the representative pollutants. The 50th percentiles of the distributions are generally near or below the analytical detection limits, and applicable Federal action limits were rarely exceeded.

Residential environmental measurements in the national human exposure assessment survey (NHEXAS) pilot study in Arizona: preliminary results for pesticides and VOCs.

A major objective of the National Human Exposure Assessment Survey (NHEXAS) performed in Arizona was to conduct residential environmental and biomarker measurements of selected pesticides (chlorpyrifos, diazinon), volatile organic compounds (VOCs; benzene, toluene, trichloroethene, formaldehyde, 1,3-butadiene), and metals for total human exposure assessments. Both personal (e.g., blood, urine, dermal wipes, 24 h duplicate diet) and microenvironmental (e.g., indoor and outdoor air, house dust, foundation soil) samples were collected in each home in order to describe individual exposure via ingestion, inhalation, and dermal pathways, and to extrapolate trends to larger populations. This paper is a preliminary report of only the microenvironmental and dermal wipe data obtained for the target pesticides and VOCs, and provides comparisons with results from similar studies. Evaluations of total exposure from all sources and pathways will be addressed in future papers. The pesticides and VOCs all showed log-normal distributions of concentrations in the Arizona population sampled, and in most cases were detected with sufficient frequency to allow unequivocal description of the concentration by media at the 90th, 75th, and 50th (median) percentiles. Those combinations of pollutant and media, in which a large fraction of the measurements were below the detection limit of the analysis method used, included trichloroethene, 1,3-butadiene, and formaldehyde in outdoor air; chlorpyrifos and diazinon in outdoor air; and diazinon in dermal and window sill wipes. In general, indoor air concentrations were higher than outdoor air concentrations for all VOCs and pesticides investigated, and VOC levels were in good agreement with levels reported in other studies. In addition, the agreement obtained between co-located VOC samplers indicated that the low-cost diffusional badges used to measure concentrations are probably adequate for use in future monitoring studies. For the pesticides, the median levels found in indoor samples agreed well with other studies, although the levels corresponding to the upper 0.1-1% of the population were considerably higher than levels reported elsewhere, with indoor air levels as high as 3.3 and 20.5 microg/m3 for chlorpyrifos and diazinon, respectively. These data showed excellent correlation (Pearson and Spearman correlation coefficients of 0.998 and 0.998, respectively) between chlorpyrifos in indoor air and in the corresponding dermal wipes, and relatively poor correlation between chlorpyrifos in dust (microg/g or microg/ml) and dermal wipes (Pearson=0.055 microg/g and 0.015 microg/m2; Spearman=0.644 microg/g and 0.578 microg/m2). These data suggest the importance of dermal penetration of semi-volatiles as a route of residential human exposure.

Evaluations of primary metals from NHEXAS Arizona: distributions and preliminary exposures. National Human Exposure Assessment Survey.

NHEXAS AZ is a multimedia, multipathway exposure assessment survey designed to evaluate metals and other analytes. This paper reports the analyte-specific concentration distributions in each of the media examined (air, soil, house dust, food, beverage, and water), for various methodologies used (inductively coupled plasma-atomic emission spectroscopy and hydride generation-atomic absorption spectroscopy). Results are reported for the five primary metals (Pb, As, Cd, Cr, and Ni). Ingestion was the most important pathway of exposure. Metal concentrations in air were very low (ng/m3) and found only above the 90th percentile. Metals were commonly found in house dust and soil. Exposure transfer coefficients minimize the importance of this component for those over the age of 6 years. When ranked by exposure, food, beverage, and water appeared to be the primary contributors of metal exposure in NHEXAS AZ. For instance, at the 90th percentile, Pb was undetected in air, found at 131 and 118 microg/m3 in floor dust and soil, respectively, and measured at 16 microg/kg in food, 7.1 microg/kg in beverage, and 2.0 and 1.3 microg/l in drinking and tap water, respectively. We calculated preliminary estimates of total exposure (microg/day) for each participant and examined them independently by age, gender, and ethnicity as reported by the subjects in the NHEXAS questionnaire. At the 90th percentile for Pb, total exposures were 64 microg/day across all subjects (n=176); adult men (n=55) had the greatest exposure (73 microg/day) and children (n=35) the least (37 microg/day). Hispanics (n=54) had greater exposure to Pb (68 microg/day) than non-Hispanics (n=119; 50 microg/day), whereas non-Hispanics had greater exposure for all other metals reported. These results have implications related to environmental justice. The NHEXAS project provides information to make informed decisions for protecting and promoting appropriate public health policy.

Underdiagnosis and undertreatment of asthma in the elderly. Cardiovascular Health Study Research Group.

OBJECTIVE: To describe the clinical correlates of asthma in a community-based sample of elderly persons. PARTICIPANTS: A community sample of 4,581 persons > or = 65 years old from the Cardiovascular Health Study. MEASUREMENTS: Standardized respiratory, sleep, and quality-of-life (QOL) questions, a medication inventory, spirometry, and ambulatory peak flow. RESULTS: Four percent of the participants reported a current diagnosis of asthma (definite asthma), while another 4% reported at least one attack of wheezing accompanied by chest tightness or dyspnea during the previous 12 months (probable asthma). Smokers and those with congestive heart failure were excluded from the subsequent analyses, leaving 2,527 participants. Of those who had definite asthma, 40% were taking a sympathomimetic bronchodilator, 30% inhaled corticosteroids, 21% theophylline, and 18% oral corticosteroids; 39% were taking no asthma medications. The participants with definite or probable asthma were much more likely than the others to have a family history of asthma, childhood respiratory problems, a history of workplace exposures, dyspnea on exertion, hay fever, chronic bronchitis, nocturnal symptoms, and daytime sleepiness. They were also more likely to report poor general health, symptoms of depression, and limitation of activities of daily living. There was little difference in the morbidity and QOL of participants with recent asthma-like symptoms who had received the diagnosis of asthma versus those who had not. CONCLUSIONS: Asthma in elderly persons is associated with a lower QOL and considerable morbidity when compared with those who do not have asthma symptoms. Asthma is underdiagnosed in this group and is often associated with allergic triggers; inhaled corticosteroids are underutilized.

Lateral diffusion of GFP-tagged H2Ld molecules and of GFP-TAP1 reports on the assembly and retention of these molecules in the endoplasmic reticulum.

Lateral diffusion of GFP-tagged H2Ld molecules in the ER membrane reports on their interaction with the TAP complex during synthesis and peptide loading. Peptide-loaded H2Ld molecules diffuse rapidly, near the theoretical limit for proteins in a bilayer. However, these molecules are retained in the ER for some time after assembly. H2Ld molecules, associated with the TAP complex, diffuse slowly, as does GFP-tagged TAP1. This implies that the association of H2Ld molecules with the TAP complex is stable for at least several minutes. It also suggests that the TAP complex is very large, perhaps containing hundreds of proteins.

Soluble, high-affinity dimers of T-cell receptors and class II major histocompatibility complexes: biochemical probes for analysis and modulation of immune responses.

T cell receptors (TCR) and major histocompatibility complex (MHC) molecules are integral membrane proteins that have central roles in cell-mediated immune recognition. Therefore, soluble analogs of these molecules would be useful for analyzing and possibly modulating antigen-specific immune responses. However, due to the intrinsic low-affinity and inherent solubility problems, it has been difficult to produce soluble high-affinity analogs of TCR and class II MHC molecules. This report describes a general approach which solves this intrinsic low-affinity by constructing soluble divalent analogs using IgG as a molecular scaffold. The divalent nature of the complexes increases the avidity of the chimeric molecules for cognate ligands. The generality of this approach was studied by making soluble divalent analogs of two different classes of proteins, a TCR (2C TCR2Ig) and a class II MHC (MCCI-Ek2Ig) molecule. Direct flow cytometry assays demonstrate that the divalent 2C TCR2Ig chimera retained the specificity of the native 2C TCR, while displaying increased avidity for cognate peptide/MHC ligands, resulting in a high-affinity probe capable of detecting interactions that heretofore have only been detected using surface plasmon resonance. TCR2IgG was also used in immunofluorescence studies to show ER localization of intracellular peptide-MHC complexes after peptide feeding. MCCI-Ek2Ig chimeras were able to both stain and activate an MCC-specific T cell hybridoma. Construction and expression of these two diverse heterodimers demonstrate the generality of this approach. Furthermore, the increased avidity of these soluble divalent proteins makes these chimeric molecules potentially useful in clinical settings for probing and modulating in vivo cellular responses.

Long-term ambient ozone concentration and the incidence of asthma in nonsmoking adults: the AHSMOG Study.

We conducted a prospective study of a cohort of 3091 nonsmokers, ages 27 to 87 years, to evaluate the association between long-term ambient ozone exposure and development of adult-onset asthma. Over a 15-year period, 3.2% of males and 4.3% of females reported new doctor diagnoses of asthma. For males, we observed a significant relationship between report of doctor diagnosis of asthma and 20-year mean 8-h average ambient ozone concentration (relative risk (RR)=2.09 for a 27 ppb increase in ozone concentration, 95% CI=1.03 to 4.16). We observed no such relationship for females. Other variables significantly related to development of asthma were a history of ever-smoking for males (RR=2.37, 95% CI=1.13 to 4.81), and for females, number of years worked with a smoker (RR=1.21 for a 7-year increment, 95% CI=1.04 to 1.39), age (RR=0.61 for a 16-year increment, 95% CI=0.44 to 0.84), and a history of childhood pneumonia or bronchitis (RR=2.96, 95% CI=1.68 to 5.03). Addition of other pollutants (PM10, SO4, NO2, and SO2) to the models did not diminish the relationship between ozone and asthma for males. These data suggest that long-term exposure to ambient ozone is associated with development of asthma in adult males.

Relation of sleepiness to respiratory disturbance index: the Sleep Heart Health Study.

Obstructive sleep apnea syndrome is a well recognized cause of excessive sleepiness; however, the relation of sleepiness to mild sleep-disordered breathing (SDB), which affects as much as half the adult population, is uncertain. In order to explore this relation, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study, a longitudinal study of the cardiovascular consequences of SDB. The study sample comprises 886 men and 938 women, with a mean age of 65 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Sleep-disordered breathing was quantified by the respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, measured during in-home polysomnography. When RDI was categorized into four groups (< 5, 5 to < 15, 15 to < 30, >/= 30), a significantly progressive increase in mean ESS score was seen across all four levels of SDB, from 7.2 (4.3) in subjects with RDI < 5 to 9.3 (4.9) in subjects with RDI >/= 30 (p < 0.001). There was no significant modification of this effect by age, sex, body mass index, or evidence of chronic restriction of sleep time or periodic limb movement disorder. The percentage of subjects with excessive sleepiness, defined as an ESS score >/= 11, increased from 21% in subjects with RDI < 5 to 35% in those with RDI >/= 30 (p < 0. 001). We conclude that SDB is associated with excess sleepiness in community-dwelling, middle-aged and older adults, not limited to those with clinically apparent sleep apnea.

Respiratory symptoms and pulmonary function in an elderly nonsmoking population.

OBJECTIVE: To examine risk factors for chronic airway disease (CAD) in elderly nonsmokers, as determined by pulmonary function tests (PFTs), and to correlate reported respiratory symptoms with PFT measures. DESIGN: An observational survey. SETTING: Several communities in California. MEASUREMENTS: Exposures and respiratory history were assessed by standardized questionnaire. PFTs were performed and prediction equations derived. RESULTS: Significant risk factors for obstruction on PFTs in multiple logistic regression included reported environmental tobacco smoke (ETS) exposure (relative risk [RR]=1.44), parental CAD or hay fever (RR=1.47), history of childhood respiratory illness (RR=2.15), increasing age, and male sex. The number of years of past smoking was of borderline significance (RR=1.29 for 10 years of smoking; p=0.06). The prevalence of obstruction on PFTs was 24.9% in those with definite symptomatic CAD, compared with 7.5% in those with no symptoms of CAD. The prevalence of obstruction was 36.0% among those with asthma and 70.6% among those with emphysema. Also, symptomatic CAD correlated with reduction in lung function by analysis of covariance. The mean percent predicted FEV1 adjusted for covariates was 90.6% in persons with definite symptoms of CAD, compared with 97.8% in those without it (p < 0.001). CONCLUSIONS: Age, sex, parental history, childhood respiratory illness, and reported ETS exposures were significant risk factors for obstruction on PFTs. Self-reported respiratory symptoms also correlated significantly with PFTs.