Epithelial cells as phagocytes: apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release.

Clearance of apoptotic cells is critical to tissue homeostasis and resolution of inflammatory lesions. Macrophages are known to remove dying cells and release anti-inflammatory mediators in response; however, many cells traditionally thought of as poor phagocytes can mediate this function as well. In the lactating mammary gland following weaning, alveolar epithelial cell death is massive, yet the gland involutes rapidly, attaining its prepregnancy state in a matter of days. We found histologic evidence of apoptotic cell phagocytosis by viable mammary epithelial cells (MEC) in the involuting mouse mammary gland. Cultured MEC were able to engulf apoptotic cells in vitro, utilizing many of the same receptors used by macrophages, including the phosphatidylserine receptor (PSR), CD36, the vitronectin receptor alpha(v)beta3, and CD91. In addition, MEC, like macrophages, produced TGFbeta in response to stimulation of the PSR by apoptotic cells or the anti-PSR ab 217G8E9, and downregulated endotoxin-stimulated proinflammatory cytokine production. These data support the hypothesis that amateur phagocytes play a significant role in apoptotic cell clearance and its regulation of inflammation.

Aggregate size distribution evolution for Brownian coagulation-sensitivity to an improved rate constant.

Brownian motion causes small aggregates to encounter one another and grow in gaseous environments, often under conditions in which the coalescence rate (say, spheroidization by "sintering") cannot compete. The polydisperse nature of the aerosol population formed by this mechanism is typically accounted for by formulating an evolution equation for the joint PDF of the state variables needed for describing individual particles. In the simple case of fractal-like aggregates (prescribed morphology and state, characterized just by the number of aggregated spherules, or total aggregate volume), we use the quadrature method of moments and Monte Carlo simulations to show that recent improvements in the laws governing free molecule regime coagulation frequency (rate "constant") of these aggregates cause systematic changes in the shape of the asymptotic aggregate size distribution, with significant implications for the light-scattering power and inertial impaction behavior of such aggregate populations.

Effective diameters for collisions of fractal-like aggregates: recommendations for improved aerosol coagulation frequency predictions.

Fractal-like aggregate (FA-) drag has been previously calculated/correlated/reported, but "mobility diameter" information is not sufficient to make rational calculations of Brownian coagulation rates (for, say, population-balance modeling). Indeed, until now, only conjectures about gyration-radius scaling behavior have been used to predict FA-FA collision cross sections! But such "scaling relations" are untrustworthy even for FA momentum-, energy-, and mass-transfer purposes, and improved FA-collision rate constants (appearing as "kernels" in the coagulation balance integro-PDE) are overdue. Our premise is that FA collision rates in the free-molecule regime can be predicted using a gas-kinetic type formulation. If (a) carrier gas mean free path and FA persistence length are much larger than any characteristic FA size, (b) FA number density is low, (c) FA velocity and position are uncorrelated, and (d) there is a "hard-sphere" interaction between primary particles of different FAs, such a theory is developed/applied here. We introduce an effective collision diameter, , depending on the geometries of the two participating FAs. Quasi-MC calculations are reported for large ensembles of pairs of FAs, each computer-generated using a tunable cluster-cluster (CC)-algorithm. Our results differ from frequently used theoretical estimates based only on FA gyration (or mobility) radii and D(f). They also confirm that, if the size disparity of the colliding FAs is large, obtained by simply assigning individual diameters to each FA are significantly overestimated. Modified collision rate expressions for FA-coagulation modeling are suggested.

Management of malignant extrinsic compression of the ureter by simultaneous placement of two ipsilateral ureteral stents.

BACKGROUND AND PURPOSE: Extrinsic ureteral obstruction caused by various malignancies often necessitates urinary diversion. The use of single ureteral stents as a form of urinary diversion results in a high failure rate, while the use of two ipsilateral stents has shown promising results. We report our experience using the latter technique. PATIENTS AND METHODS: Between 1996 and 2001, four male and three female patients with a mean age of 65 years (range 37-95 years) who had extrinsic compression of the ureters underwent single stent management to relieve obstruction. Ureteral obstruction was secondary to prostate cancer (N = 3), cervical cancer (2), non-Hodgkin's lymphoma (1), and transitional-cell cancer of the bladder and ureter (1). After failure of such management, two 7F stents or a combination of 8F/6F double-J ureteral stents were placed. The stents were changed every 4 to 6 months. Follow-up included serial renal ultrasound scans and serum creatinine measurements. RESULTS: Ureteral stricture length ranged from 2 to 4 cm. Insertion of two double-J ureteral stents in a single ureter was successful in all cases. During the mean follow-up of 16 months (range 1-38 months), the ureteral stents were tolerated by all patients, without significant discomfort. Marked improvement of hydronephrosis and alleviation of flank pain was noted in all patients. Three patients have died at 1 to 3 months. Renal function improved, with a mean decline in the serum creatinine concentration from 3.2 mg/dL to 1.48 mg/dL in the five patients tested. CONCLUSION: Simultaneous placement of two double-J ureteral stents for the management of ureteral obstruction secondary to a malignancy is a safe and effective technique.

Characterization of a Mycobacterium smegmatis mutant that is simultaneously resistant to D-cycloserine and vancomycin.

A mutant of Mycobacterium smegmatis has been isolated that is simultaneously resistant to both D-cycloserine (D-CS) and vancomycin. Genetic complementation with a PBP4 homolog restores sensitivity to both drugs. Resistance to D-CS and vancomycin in this mutant is most likely due to a novel mechanism involving peptidoglycan assembly at the cell surface.

"Cater to the children": the role of the lead industry in a public health tragedy, 1900-1955.

A major source of childhood lead poisoning, still a serious problem in the United States, is paint. The dangers of lead were known even in the 19th century, and the particular dangers to children were documented in the English-language literature as early as 1904. During the first decades of the 20th century, many other countries banned or restricted the use of lead paint for interior painting. Despite this knowledge, the lead industry in the United States did nothing to discourage the use of lead paint on interior walls and woodwork. In fact, beginning in the 1920s, the Lead Industries Association and its members conducted an intensive campaign to promote the use of paint containing white lead, even targeting children in their advertising. It was not until the 1950s that the industry, under increasing pressure, adopted a voluntary standard limiting the amount of lead in interior paints.

When does a worker's death become murder?

During the past 2 decades, a growing number of manslaughter and even murder charges have been brought against employers in cases involving the death of workers on the job. In this commentary, the author reviews some of these recent cases and looks at other periods in American history when workers' deaths were considered a form of homicide. He examines the social forces that shape how we define a worker's death: as an accidental, chance occurrence for which no individual is responsible, or as a predictable result of gross indifference to human life for which management bears criminal responsibility. He asks whether there is a parallel between the conditions of 19th-century laissez-faire capitalism that led to popular movements promoting workplace safety and the move in recent decades toward deregulation and fewer restraints on industry that has led state and local prosecutors to criminalize some workplace accidents. Despite an increased federal presence, the activities of state and local district attorneys perhaps signal a redefinition of the popular understanding of employers' responsibility in maintaining a safe workplace.

Analysis of case-cohort designs.

The case-cohort design is most useful in analyzing time to failure in a large cohort in which failure is rare. Covariate information is collected from all failures and a representative sample of censored observations. Sampling is done without respect to time or disease status, and, therefore, the design is more flexible than a nested case-control design. Despite the efficiency of the methods, case-cohort designs are not often used because of perceived analytic complexity. In this article, we illustrate computation of a simple variance estimator and discuss model fitting techniques in SAS. Three different weighting methods are considered. Model fitting is demonstrated in an occupational exposure study of nickel refinery workers. The design is compared to a nested case-control design with respect to analysis and efficiency in a small simulation. In this example, case-cohort sampling from the full cohort was more efficient than using a comparable nested case-control design.

Labor Day and the war on workers.

We celebrate Labor Day every year with barbecues and picnics, rarely remembering that the holiday was born in the midst of tremendous labor struggles to improve working conditions. In the last century, 16-hour workdays and 6- and 7-day workweeks led to terribly high injury rates in the nation's mines and mills. Thousands upon thousands of workers died, caught in the grinding machinery of our growing industries. Today, despite improvements, thousands of workers still die in what has been described as a form of war on the American workforce. This commentary reminds us of the historical toll in lives and limbs that workers have paid to provide us with our modern prosperity. It also reminds us that the continuing toll is far too high and that workers who died and continue to die in order to produce our wealth deserve to be remembered and honored on this national holiday.

Occupational exposure to electromagnetic fields and Alzheimer disease.

The association between occupational exposure to electromagnetic fields (EMF) and Alzheimer disease (AD) was examined. Subjects were identified from a large health maintenance organization in Seattle, Washington, and matched by age, sex, and proxy type. A complete occupational history was obtained from proxies and controls. Following the interview, two industrial hygienists (IHs) rated exposures to EMF for each job blinded to case-control status. Exposures to EMF were rated as probable intermittent exposure or probable exposure for extended periods to levels above threshold. Conditional logistic regression was used to calculate the risk of AD given EMF exposure stratified by IH. The odds ratios for ever having been exposed to EMF were 0.74 [95% confidence interval (CI) 0.29-1.92] and 0.95 (95% CI 0.27-2.43) for each IH, adjusting for age and education. No dose-response effect was noted. Agreement between the two IHs for ever having been exposed to EMF was good (kappa = 0.57, p < 0.0001). This study was unable to support an association between EMF and AD.

In situ light-scattering measurements of morphologically evolving flame-synthesized oxide nanoaggregates.

Nonspherical Al2O3 aggregates produced in a laminar counterflow nonpremixed methane flame were investigated with an in situ laser light-scattering (LLS) technique in combination with a thermophoretic sampling-transmission electron microscope (TS-TEM) method. These flame-synthesized nanoparticles clearly underwent morphological changes following their formation (from precursor trimethylaluminum hydrolysis), mainly as a result of aggregation and sintering processes in the approximately 3.3 x 10(4) K/s heating environment. To characterize this particulate morphological evolution conveniently we made multiangular absolute LLS measurements and interpreted them based on the Rayleigh-Debye-Gans scattering theory for fractal aggregates. Optically determined fractal dimension D(f), mean radius of gyration, aggregate size distribution, and local particle volume fraction phi(p) were found to be consistent with our independent ex situ TS-TEM experiments. D(f) (optically inferred) increased from 1.60 to 1.84 with axial position, confirming the morphological evolution of alumina aggregates owing to finite-rate, spatially resolved high-temperature sintering. An extension of our TS-TEM method was successfully applied, for the first time to our knowledge, to inorganic particles. Phi(p) inferred by means of this ex situ technique generally agreed with that from the in situ LLS technique, supporting our interpretation of both measurements. Moreover, an optically inferred net sintering rate of alumina aggregates approaching the flame was estimated to be consistent with the available TEM data. The LLS methods and results presented here are expected to permit more comprehensive mechanistic analyses of nanoaggregate sintering and coagulation kinetics in such flame environments, ultimately improving the modeling of more-complex (e.g., turbulent, high-pressure) combustion systems involving nanoparticle formation and evolution.

The reawakening of national concern about silicosis.

From West Texas to West Virginia, from California to New York, in industries from oil refining to coal mining and work settings from foundries to shipyards, the United States is experiencing an epidemic of silicosis, a preventable disease. Silica sand has been linked to cancer, and the International Agency for Research on Cancer has named silica as a probable human carcinogen. This article analyzes the reawakening of national concern about silicosis and the social, economic, and epidemiologic factors that have led scientists, policy makers, industrial hygienist, and labor and industry representatives to reassess the danger that silica sand poses to the health of an estimated two million workers in this country.

Occupational exposures to solvents and aluminium and estimated risk of Alzheimer's disease.

OBJECTIVES: To study the role of occupational exposures to solvents and aluminium in the aetiology of Alzheimer's disease (AD). An industrial hygienist rated exposure. METHODS: 89 subjects diagnosed with probable AD were matched by age, sex, and type of informant to 89 controls. Subjects were identified from a large health maintenance organisation in Seattle, WA. A complete occupational history was obtained from spouses of cases and controls as well as from controls themselves. After the interview an industrial hygienist, blinded to case-control status, rated exposures. RESULTS: Non-significant associations were found between AD and ever having been occupationally exposed to solvents (odds ratio (OR) 1.77, 95% confidence interval (95% CI) 0.81 to 3.90) and aluminium (OR 1.46, 95% CI 0.62 to 3.42). Although an increasing risk was found with increasing number of years of exposure to solvents, there was an inverse association between exposure intensity and AD, and measures of cumulative exposure taking into account both intensity and duration of exposure were not significant. Analysis of the age at which half the cumulative exposure to solvents was achieved showed that an older age incurred a greater risk of AD than a younger age. However, the total amount of exposure carried no risk. CONCLUSIONS: The results suggest that lifetime occupational exposure to solvents and aluminium are not likely to be important risk factors for Alzheimer's disease.

Use of health services by children of smokers and nonsmokers in a health maintenance organization.

OBJECTIVES: Use of health services by children of smokers and nonsmokers was compared to assess whether exposure to environmental tobacco smoke resulted in greater use of health services among children of smokers. METHODS: Primary care and emergency room visits, asthma-related prescriptions, and inpatient stays over the 42-month study period were compared for children of smokers (n = 498) and nonsmokers (n = 1062) who were enrolled in a health maintenance organization. Parents of children aged 1 through 11 years were identified from participants in 2 randomized smoking cessation trials. RESULTS: After adjustment for parental age, education, and health status and for child's age, there were no differences between children of smokers and children of nonsmokers in use of primary care or emergency room visits, asthma-related prescriptions, or inpatient stays. However, among those with any preventive care visits, children of smokers had significantly fewer visits than children of nonsmokers. CONCLUSIONS: Further study is needed to elucidate whether parents who smoke underutilize health services for their children or use services differently from nonsmoking parents and whether these differences have cost implications.