Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.

LL37 exerts a dual pathogenic role in psoriasis. Bound to self-DNA/RNA, LL37 licenses autoreactivity by stimulating plasmacytoid dendritic cells-(pDCs)-Type I interferon (IFN-I) and acts as autoantigen for pathogenic Th17-cells. In systemic lupus erythematosus (SLE), LL37 also triggers IFN-I in pDCs and is target of pathogenic autoantibodies. However, whether LL37 activates T-cells in SLE and how the latter differ from psoriasis LL37-specific T-cells is unknown. Here we found that 45% SLE patients had circulating T-cells strongly responding to LL37, which correlate with anti-LL37 antibodies/disease activity. In contrast to psoriatic Th17-cells, these LL37-specific SLE T-cells displayed a T-follicular helper-(TFH)-like phenotype, with CXCR5/Bcl-6 and IL-21 expression, implicating a role in stimulation of pathogenic autoantibodies. Accordingly, SLE LL37-specific T-cells promoted B-cell secretion of pathogenic anti-LL37 antibodies in vitro. Importantly, we identified abundant citrullinated LL37 (cit-LL37) in SLE tissues (skin and kidney) and observed very pronounced reactivity of LL37-specific SLE T-cells to cit-LL37, compared to native-LL37, which was much more occasional in psoriasis. Thus, in SLE, we identified LL37-specific T-cells with a distinct functional specialization and antigenic specificity. This suggests that autoantigenic specificity is independent from the nature of the autoantigen, but rather relies on the disease-specific milieu driving T-cell subset polarization and autoantigen modifications.

Solvent exposures in screen printing shops.

A comprehensive description of working conditions, exposure patterns for organic solvents, and related health symptoms among workers in ten small screen printing companies located in Seattle, Washington, is presented. Sampling methods included continuous area monitoring, grab sampling, personal sampling, and time study observation. A total of 27 workers were observed and monitored for solvent exposure. Short-term peak exposures were characterized in terms of magnitude, duration and repetition, and their contribution to time weighted average (TWA) exposures were evaluated. A health questionnaire addressing the symptoms potentially attributable to solvents was used to investigate the possible health effects from exposure. Significant differences in the prevalence of headaches, dizziness, intoxication, and dry skin (p < 0.01) were reported among workers who had some solvent exposure compared with the referent group that was not exposed. Exposed workers were also more likely to report fatigue, loss of strength in the arms and hands, difficulty concentrating, sore throat, and a low alcohol tolerance. The study documented highly variable levels of solvent exposures. Screen printing workers in different companies, while performing the same basic tasks, had time weighted average (TWA) exposures ranging from 2% to 100% of the recommended threshold limit value (TLV) for mixtures. Continuous monitoring indicated that high short-term exposures are responsible for the bulk of TWA exposures. Grab samples and continuous monitoring verified that recommended Short Term Exposure Limits (STEL) for individual solvents may be exceeded on a routine basis. Frequent skin contact with solvents was also observed. Health problems in this industry and other small industries using organic solvents may result from these complex patterns of exposure.

Triazine herbicide exposure and breast cancer incidence: an ecologic study of Kentucky counties.

The incidence of breast cancer in the United States has steadily increased for the past three decades. Exposure to excess estrogen, in both natural and synthetic forms, has been implicated as a risk factor for the development of this disease. Considerable interest has been focused on organochlorines, such as the triazine herbicides, and their possible role in the initiation or promotion of human breast cancer. To explore this relationship, an ecologic study of Kentucky counties was designed. Exposure to triazines was estimated by use of water contamination data, corn crop production, and pesticide use data. A summary index of triazine herbicide exposure was developed to classify counties into low, medium, or high exposure levels. Data on county breast cancer rates were obtained from the state registry. A Poisson regression analysis was performed, controlling for age, race, age at first live birth, income, and level of education. Results revealed a statistically significant increase in breast cancer risk with medium and high levels of triazine exposure [odds ratio (OR) = 1.14,p<0.0001 and OR = 1.2, p<0.0001, respectively]. The results suggest a relationship between exposure to triazine herbicides and increased breast cancer risk, but conclusions concerning causality cannot be drawn, due to the limitations inherent in ecologic study design.

Arsenic poisoning in central Kentucky: a case report.

A recent case of chronic arsenic intoxication due to prolonged accidental ingestion of a commercially available crabgrass killer illustrates one of the more common etiologies of present day arsenic poisoning. A review of 20 years of arsenic poisoning at the University of Kentucky (21 cases) revealed no cases attributable to an industrial source. A tabulation of the 21 most recent cases is included.

Environmental equity and pesticide exposure.

Although people of color and low-income groups bear a disproportionate share of the health risks from exposure to pesticides, research attention has been meager, and data on acute and chronic health effects related to their toxic exposures are generally lacking. Increased resources are needed both to study this issue and to mitigate problems already identified. People of color should be a major research focus, with priority on long-term effects, particularly cancer, neurodevelopmental and neurobehavioral effects, long-term neurological dysfunction, and reproductive outcome. Suitable populations at high risk that have not been studied include noncertified pesticide applicators and seasonal and migrant farm workers, including children.

Neuropsychological performance and solvent exposure among car body repair shop workers.

A cross sectional study to evaluate symptom reporting and neuropsychological test performance among a cohort of car body repair workers (n = 124) was performed using a computer-administered test system. Subjects with high and medium current exposures to solvent and paint (n = 39 and 32), and low exposure subjects who formerly painted (n = 29) reported significantly more acute and chronic neurological symptoms than did low exposure subjects with no history of painting (n = 24). Subjects with higher current exposure performed significantly less well on selected tests of visual perception and memory, but there were no significant exposure related differences in mood state, motor speed, or visuomotor performance. The exposure related effects were most noticeable among subjects 35 years or older. The findings are consistent with age interactive central neurotoxic effects of current exposure to solvents or of cumulative past exposure, although the study is unable to distinguish between these possibilities. The computer administered test system was effective in this field based investigation involving multiple, geographically dispersed worksites.

Organophosphate pesticide exposure in a group of Washington State orchard applicators.

As part of a study to investigate the potential for organophosphates to cause chronic neurologic sequelae, we assessed the pesticide exposure experience of a group of Washington State apple orchard applicators. Seasonal monitoring of cholinesterase activity for 48 regular organophosphate applicators and a control group of 40 slaughterhouse workers was performed. A subset of the pesticide applicators participated in an in-depth exposure assessment. This involved observation of spraying activities during 1 spray day, as well as cholinesterase monitoring and dermal exposure assessment using a fluorescent tracer in the pesticide formulation. Comparison of seasonal red blood cell cholinesterase change in pesticide workers according to exposure level, characterized by frequency of pesticide spraying and protective equipment use, showed lower cholinesterase levels among higher exposed groups compared to lesser exposed groups. In-depth exposure assessment revealed exposure primarily on the head and hand regions. Subclinical changes (less than 15% inhibition) in red cell cholinesterase correlated well with dermal exposure calculations. This study suggests that cholinesterase monitoring may be a useful biological marker for even subclinical organophosphate pesticide effects.

Cobalt exposure in a carbide tip grinding process.

Reports relating hard metal disease or nonspecific respiratory symptoms to tungsten or cobalt exposure have been published in the past 20 yr. This report discusses a work site investigation of a small company, employing approximately 50 workers, producing carbide tip saw blades for the woodworking industry. Cobalt exposure was characterized by ambient air monitoring (area and personnel), particle size determination, and biological monitoring. Area sampling for cadmium, cobalt, and tungsten indicated low ambient air levels in all manufacturing areas except the grinding department, which had cobalt air levels approaching the threshold limit value of 0.05 mg/m3. Area airborne cobalt exposure levels measured over six shifts in the grinding department ranged from 0.017 to 0.12 mg/m3 for the total collection method and 0.002 to 0.028 mg/m3 for the method collecting respirable particles. Cobalt content in the total and respirable fractions was similar. Urine monitoring indicated production workers have elevated cobalt levels, and the grinders' levels were higher than other production workers. The grinding coolant was found to have elevated cobalt concentrations. A survey of coolants from nine carbide grinding shops indicated the elevated cobalt concentrations may be common.

The contributions to solvent uptake by skin and inhalation exposure.

Solvent exposures were assessed among 97 auto body repair workers in order to determine whether skin contact represented a significant route of exposure. Each subject's cumulative skin exposure was ranked categorically based on simple observation: 49 none, 33 incidental or low, and 15 moderate or high. The median time-weighted average air exposure to solvents was 8.4% of the American Conference of Governmental Industrial Hygienists (ACGIH) combined solvent threshold limit value (TLV) with a range of 0-62% TLV, including toluene (median 4 ppm) and xylenes (median 0.9 ppm). Urine methyl hippuric acids (MHAs, metabolites of xylenes) were low compared to the ACGIH biological exposure index (BEI) with a median of 2% and a range of 0-12% BEI but were strongly correlated with both the level of airborne xylenes and skin exposure when considered simultaneously by using analysis of covariance (R = 0.91, p less than 0.0001). MHA excretion attributable to skin exposure for 15 min or more generally was comparable to or greater than that from associated air exposure over the full work shift. This study had limited ability to assess quantitatively the contributions of toluene exposures, but there was evidence that skin exposures also contributed significantly to toluene absorption. Air sampling will substantially underestimate a worker's total solvent dose in the setting of moderate or high skin exposure. Simple observation was effective in identifying workers in this sample who appeared to have sufficient skin exposure to produce a measurable increase in solvent uptake.

Impact of prostaglandin and thromboxane synthesis blockade on disposition of group B streptococcus in lung and liver of intact piglet.

Group B streptococci (GBS) localizing in the lungs of infant piglets is killed in part by an oxygen radical-dependent mechanism (Bowdy BD, Marple SL, Pauly TH, Coonrod JD, Gillespie MN: Am Rev Respir Dis 141:648-653, 1990). The source of bactericidal oxygen radicals is unknown, but cyclooxygenation of arachidonic acid, an initial event in prostanoid synthesis, is accompanied by substantial oxygen radical generation. Because blockade of prostaglandin H synthase (cyclooxygenase) with indomethacin prevents GBS-induced pulmonary hypertension, we reasoned that the salutary effect of indomethacin might be associated with a reduction in the efficacy of bactericidal activity directed against GBS. To address this possibility, the distribution and viability of 111In-labeled GBS (10(8) colony forming units/kg/min i.v. for 15 min) were assessed in lungs and livers of control piglets, piglets treated with indomethacin (1 mg/kg), and piglets treated with OKY-046 (10 mg/kg), an inhibitor of thromboxane synthase that also forestalls GBS-induced pulmonary hypertension. Relative to control animals, indomethacin treatment increased pulmonary GBS uptake with no change in bacterial distribution into the liver. OKY-046 failed to influence pulmonary bacterial uptake but promoted a substantial increase in GBS depositing in the liver. In contrast to its effects on pulmonary bacterial deposition, indomethacin failed to increase lung bacterial viability relative to control animals. Indomethacin also was without effect on hepatic bacterial viability. OKY-046 failed to influence pulmonary bacterial viability but markedly augmented hepatic GBS viability to the extent that significant bacterial proliferation occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Trial of a negative ion generator device in remediating problems related to indoor air quality.

It has been suggested that supplementation of indoor air with negative ions can improve air quality. This study examined the effects of a "negative ion-generator" device on air contaminants and symptom reporting in two office buildings. Separate sets of functional and nonfunctional negative ion generators were monitored using a double blind, crossover design involving two 5-week exposure periods. There were no detectable direct or residual effects of negative ion generator use on air ion levels, airborn particulates, carbon dioxide levels, or symptom reporting. Symptom reporting declined at both sites initially and appeared to be consistent with placebo effect. Job dissatisfaction was an apparent contributor to symptom reporting, with a magnitude comparable to presumed effects of air quality. Further testing of such devices is needed before they should be considered for office air quality problems.

Dimethylthiourea reverses sepsis-induced pulmonary hypertension in piglets.

Dimethylthiourea (DMTU), a putative hydroxyl radical scavenger, attenuates thromboxane generation and pulmonary hypertension in the piglet model of group B streptococcal (GBS) sepsis. This study tested the hypothesis that DMTU reverses ongoing GBS-induced pulmonary hypertension coincident with decreased thromboxane production. Piglets (n = 15) received a 60 min infusion of GBS (10(-8) cfu/kg/min). Mean pulmonary artery pressure (Ppa), arterial blood gases (ABGs), and thromboxane B2 (TXB) levels were measured at 10 min intervals throughout the study. GBS infusion resulted in a marked increase in pulmonary artery pressure (mean delta Ppa = 31 mm Hg) and a significant decline in PaO2 (mean = -80 torr) within 10 min of beginning the infusion. pH decreased from a mean of 7.47 to 7.37. DMTU, 750 mg/kg, or normal saline vehicle was infused over 10-15 min beginning 10 min after initiating GBS. Ppa decreased significantly within 10 min of DMTU infusion. Piglets receiving vehicle had a slow decline in Ppa. Piglets receiving DMTU also had an improvement in PaO2 and showed no further drop in pH. Piglets receiving vehicle had no improvement in PaO2 and demonstrated a continued decline in pH. TXB levels did not differ between the groups at any time interval. We conclude that DMTU can partially reverse GBS-induced pulmonary hypertension, but may function through mechanisms independent of thromboxane generation.

Group B streptococcus promotes oxygen radical-dependent thromboxane accumulation in young piglets.

Both thromboxane A2 and oxygen-derived free radicals appear to play central roles in group B streptococcus (GBS)-induced pulmonary hypertension in piglets. This study tested the hypothesis that GBS promotes oxygen radical-dependent thromboxane accumulation and pulmonary hypertension in infant piglets. Piglets 4-12 d old were anesthetized and prepared for assessment of pulmonary arterial pressure and arterial blood gases. In control animals, GBS (10(8) organisms/kg/min for 15 min) increased mean pulmonary artery pressure by 30 +/- 1.5 torr and reduced arterial PO2 by 100 +/- 20 torr. Thromboxane A2, radioimmunoassayed in venous blood as thromboxane B2, increased by 2452 +/- 800 pg/mL. A second group of piglets was treated with dimethylthiourea (DMTU: 750 mg/kg), a putative oxygen radical scavenger. In these animals, GBS increased pulmonary arterial pressure by only 7 +/- 1 torr and reduced arterial PO2 by a modest 10 +/- 8 torr. Importantly, thromboxane B2 content in venous blood failed to increase above control levels in DMTU-treated animals. The protective effects of DMTU in GBS-treated piglets could not be ascribed to inhibition of cyclooxygenase or thromboxane synthase because the oxygen radical scavenger failed to attenuate increases in pulmonary arterial pressure and venous thromboxane B2 content or reductions in arterial PO2 caused by i.v. infusions of arachidonic acid. DMTU also did not ameliorate pulmonary hypertension evoked by the thromboxane mimetic U44069, thereby suggesting that the scavenger did not act as an end-organ antagonist of thromboxane receptors. These observations suggest that GBS promotes accumulation of thromboxane A2 and attendant pulmonary hypertension through an oxygen radical-dependent mechanism.

Industrial hygiene, chemical and biological assessments of exposures to a chlorinated phenolic sapstain control agent.

A two-year study of the occupational exposure of workers in a lumber mill to a wood preservative containing chlorophenol has been conducted. The methods were biological (urine) monitoring, industrial hygiene assessment and a questionnaire related to worker-perceived health effects. Approximately 40 workers exposed to the wood preservative and 40 unexposed controls working in other locations of the plant participated in the study. Evaluation of work conditions, assessment of urinary levels of tetra- and pentachlorophenol, and administration of a medical questionnaire were performed at a six-month intervals over a two-year period. Industrial hygiene ratings of exposures and adequacy of protection were evaluated in relation to the results of biological monitoring. Workers who came into contact with freshly treated and still wet wood had consistently higher urinary levels of tetrachlorophenol. Workers stationed adjacent to the spray applicator also had higher tetrachlorophenol levels. There was no statistically significant relationship between the subjective ratings by the industrial hygienist of exposure and adequacy of worker protection with the urinary levels of tetrachlorophenol. Nor was there a consistent pattern linking exposure ratings with adequacy of protection. The short half-life of tetrachlorophenol in the urine makes this a good indicator of only the most recent exposure. The differences in urinary levels between controls and exposed workers were large, with averages of 240.4 ppb for exposed workers and 14.6 for controls. Traditional industrial hygiene evaluation techniques, in conjunction with biological monitoring, proved to be the most effective method of assessing both exposure and work practices. Exposed workers reported a statistically significant increase of positive answers to known signs and symptoms of chlorophenol exposure compared with the controls. There was no statistically significant relationship between the number of these health problems reported and the mean urinary levels of tetra- or pentachlorophenol for the exposed group; however, for certain variables (heavy vs. light exposure, inadequate vs. adequate protection, greater than 100 ppb urinary tetrachlorophenol vs. less than 100 ppb), those with heavier exposure, inadequate protection or higher urinary tetrachlorophenol reported on the average more health problems over the two-year period. Firm statistical conclusions could not be drawn because of the small size of the study population.

Permeation through five commercially available glove materials by two pentachlorophenol formulations.

Five glove materials were tested for permeation by two commonly used formulations of pentachlorophenol (PCP). Permeation was conducted using the method used in two prior studies by NIOSH. The lower limit of PCP quantitation in the receiving side of the permeation cell was 70 parts per billion (ppb). When challenged with a 4.3% PCP in diesel oil solution, both the Dayton Flexible Products Triflex (PVC) and the Best 64 NFW (natural rubber) gloves exhibited breakthrough times thirty seconds after exposure. The Playtex #835 (latex/neoprene) glove exhibited breakthrough after sixty minutes, but showed a five fold greater rate of permeation than the Dayton and the Best glove. Neither the Edmont Sol-Vex (nitrile rubber) nor the Granet Glo-Gluv (PVC) gloves had been permeated after testing for 8 and 16 hours respectively. Following challenge with a 4.2% sodium pentachlorophenate solution, only the Best (natural rubber) glove allowed breakthrough; this only thirty seconds after exposure. Neither the Dayton (5 hours), Playtex (7.5 hours), Edmont (15.5 hours), nor Granet (15.5 hours) gloves had been permeated following completion of testing after the listed duration. This study has shown that different gloves offer differing resistance to permeation by PCP based upon the composition of the glove and the PCP formulation tested.

Persistence of tetrachlorophenol and pentachlorophenol in exposed woodworkers.

The decline in urinary concentrations of pentachlorophenol (PCP) and 2,3,4,6-tetrachlorophenol (TCP) were observed for a group of woodworkers chronically exposed to Permatox 100 (3% PCP, 21% TCP) during a 16 day vacation and plant shutdown. The group was monitored annually for two years, with sampling occurring on the last working day prior to shutdown and on the first day after the shutdown. Among those workers with the highest pre-shutdown levels, uniform TCP reductions of 90 +/- 6% were observed, indicating elimination rates similar to those reported for PCP in a single dose human exposure study. Four workers were sampled on alternate days during the shutdown in the second year. Of these, two workers had significant pre-shutdown levels, and showed declines in urine TCP levels over this period consistent with simple one-compartment first order decay. The possible effect of environmental PCP exposure on observed biological decay rates when occupational PCP exposures are low was indicated by the wide variation in urinary PCP reduction and slight decreases or actual increases observed over the shutdown period.

Health complaints attributed to the use of carbonless copy paper (a preliminary report).

Persistent health complaints attributed to the use of carbonless copy paper by office workers on the campus of the University of Washington led to this preliminary study. The goals were to estimate the extent of the problem in a population of known carbonless copy paper users; to describe those health problems which the users attribute to the use of carbonless copy paper; and to make a preliminary determination of the chemical constituents of the paper. Participants were asked to complete a health questionnaire and to attach to it copies of the forms they used. A minimum estimate of 10.7 health complainants per 100 users was similar to that found by investigators in Denmark, but lower than that reported by other investigators and of anecdotal material reported to the study group. There was a statistically significant association between complainants and the amount of paper used. Reports of headaches and irritation of the skin, eye and respiratory tract were similar to those reported elsewhere. Concurrent factors such as poor ventilation, high temperature and/or low humidity need to be investigated for possible synergistic or additive effects.

A critical evaluation of the protection provided by common safety glasses from ultraviolet emissions in welding operations.

The purpose of this investigation was to evaluate critically several brands of safety spectacle lens and side shield combinations to determine their attenuation characteristics for ultraviolet (UV) radiation. By combining the information developed in this investigation with field data on UV from arc welding operations, it was possible to draw the conclusion that under the conditions stated, ordinary safety glasses with solid side shields provided adequate eye protection from UV.

Investigation of a dual filter sampling method for gaseous and particulate fluoride.

A two stage filter method designed to separate gaseous and particulate fluoride utilizing an alkaline treated filter to trap gaseous fluoride and post sampling heat treatment of the filters to promote desorption of gaseous fluoride from particulate phase was compared to standard impinger methods for the collection of hydrogen fluoride. Results indicate a high degree of comparability between the two methods. Initial studies involving the recovery of HF from dusted filters by heat treatment suggest recovery rates may vary directly with the amount of HF sampled for a given dust load.