Considerations regarding the collection of pesticide use information for regulatory purposes

Proper use information is necessary to do exposure modelling in the scope of regulatory risk assessments. The legal regime under which the regulatory risk assessment is done influences the need for use information. Different legal regimes lead to more or less possibilities for authorities to define the exposure scenario to be assessed and the data to be presented by the industrial parties involved. The more information is required by the regulations, the less use information has to be gathered or guessed at by the regulatory exposure assessor. The value of use information is further determined by the scope of the assessment. A very conservative first tier (screening) assessment requires little information, whereas a detailed assessment of actual risks requires accurate use information. The scientific knowledge and available models limit the benefits of use information. Interesting use information has little value if there are no methods to account for the information in the exposure assessment, e.g. if relations between possible exposure determinants and exposure levels are unknown. The need for use information will further be dependent on the analysis of costs (of gathering data) versus benefits (increase in quality of the assessment). Many choices regarding the need for use information depend on policy choices by decision-makers. These decision-makers again depend on proper scientific information to make informed choices.     

Complement activation by malignant B cells from patients with chronic lymphocytic leukaemia (CLL).

It has previously been reported that the expression of the complement receptors CR1 (CD35) and CR2 (CD21) on malignant B cells in CLL is reduced compared with the expression on normal B cells, while deposition of complement C3 fragments, as a consequence of alternative pathway (AP) activation of complement, is observed on mononuclear cells from patients with B CLL. Following our demonstration that normal B cells are capable of activating the AP of complement in a CR2-dependent fashion, we have chosen to re-examine the complement-activating ability of B CLL cells in relation to their altered phenotype with respect to CR2 and the complement regulatory membrane proteins, CR1, decay accelerating factor (DAF) (CD55) and membrane cofactor protein (MCP) (CD46). Flow cytometry was used to measure expression of complement receptors and regulatory proteins on CD5+ B cells from CLL patients, as well as the deposition of C3 fragments occurring both in vivo and after in vitro AP activation. We have confirmed the reduced expression of CR1 and CR2 on CLL cells and have shown that AP activation in the presence of homologous, normal serum was reduced on B CLL cells compared with normal B cells. The degree of AP activation correlated directly with CR2 expression. In addition, we observed that CLL cells bear in vivo-deposited C3d,g, although at a significantly lower level than normal B cells.     

Pseudomonas keratitis: protease IV gene conservation, distribution, and production relative to virulence and other Pseudomonas proteases

PURPOSE: To determine the distribution of the protease IV gene, the production of this and other proteases by multiple strains of Pseudomonas, and the virulence of a mutant specifically deficient in protease IV. METHODS: The protease IV gene was cloned, its sequence analyzed, and its chromosomal location determined by pulse-field gel electrophoresis. Three PCR reactions were used to detect the protease IV gene in 30 Pseudomonas isolates and protease production was determined by Western blot analysis, colorimetric assay, and zymography. An allelic replacement mutant deficient in the protease IV gene was analyzed for enzyme production, corneal growth, and corneal virulence. RESULTS: The protease IV gene was identified in all P. aeruginosa, but none of the non-aeruginosa strains tested. The protease IV genes of strains PA103-29 and PAO1 were in a common chromosomal site and had 98.5% sequence identity with variations occurring mainly in the promoter region. The protease IV activity of the 23 wild-type P. aeruginosa strains tested varied from 2.3 to 221.5 x 10(-3) U/mg protein in the culture supernatant. Protease IV was produced by all P. aeruginosa wild-type strains. A protease IV-deficient mutant derived from strain PA103-29 had reduced virulence compared with its parent strain and unexpectedly produced alkaline protease. CONCLUSIONS: The protease IV gene and its product are common to P. aeruginosa, but not to other Pseudomonas species. Protease IV activity varies among P. aeruginosa strains, and a mutant specifically deficient in this activity produced alkaline protease and had reduced corneal virulence.     

Disparities in young adolescent inhalant use by rurality, gender, and ethnicity

Inhalant use is of increasing concern as rates appear to be rising among young adolescents and gender differences narrowing. Data from 20,684 Mexican American and White non-Hispanic seventh- and eighth-grade males and females from the Western United States and 15,659 African American and White non-Hispanic seventh- and eighth-grade males and females from states in the southeastern United States collected via in-school surveys from 1996 to 2000 were analyzed using a variety of statistical techniques including multilevel modeling. Questions addressed in the study included: Does inhalant use vary by level of rurality? What effect does the ethnic composition of the community have on inhalant use and does this effect differ by an individual's ethnicity? Do males use more inhalants than females and does the level of use by males and females differ by individual ethnicity, ethnicity of the community, or level of rurality? Do males and females of different ethnicities initiate inhalant use at different ages? Limitations of the study and implications of findings for prevention are discussed and areas of future research are suggested. This study was funded by the National Institute on Drug Abuse.     

Binding characteristics of thrombin-activatable fibrinolysis inhibitor to streptococcal surface collagen-like proteins A and B

Streptococcus pyogenes is the causative agent in a wide range of diseases in humans. Thrombin-activatable fibrinolysis inhibitor (TAFI) binds to collagen-like proteins SclA and SclB at the surface of S. pyogenes. Activation of TAFI at this surface redirects inflammation from a transient to chronic state by modulation of the kallikrein/kinin system. We investigated TAFI binding characteristics to SclA/SclB. Thirty-four overlapping TAFI peptides of ~20 amino acids were generated. Two of these peptides (P18: residues G205-S221, and P19: R214-D232) specifically bound to SclA/SclB with high affinity, and competed in a dose-dependent manner with TAFI binding to SclA/SclB. In another series of experiments, the binding properties of activated TAFI (TAFIa) to SclA/SclB were studied with a quadruple TAFI mutant (TAFI-IIYQ) that after activation is a 70-fold more stable enzyme than wild-type TAFIa. TAFI and TAFI-IIYQ bound to the bacterial proteins with similar affinities. The rate of dissociation was different between the proenzyme (both TAFI and TAFI-IIYQ) and the stable enzyme TAFIa-IIYQ. TAFIa-IIYQ bound to SclA/SclB, but dissociated faster than TAFI-IIYQ. In conclusion, the bacterial proteins SclA and SclB bind to a TAFI fragment encompassing residues G205-D232. Binding of TAFI to the bacteria may allow activation of TAFI, whereafter the enzyme easily dissociates.     

Corneal virulence of Pseudomonas aeruginosa elastase B and alkaline protease produced by Pseudomonas putida

PURPOSE: To measure the specific virulence contributions of two Pseudomonas aeruginosa proteases, elastase B and alkaline protease, when expressed separately by Pseudomonas putida in a rabbit model of bacterial keratitis. METHODS: P. putida KT2440 was transformed with plasmids that enabled the extracellular production of either elastase or alkaline protease. Protease expression was confirmed by zymography and immunoblotting. P. putida expressing elastase, alkaline protease, or vector alone was injected intrastromally (10(3) colony forming units [CFU]) into rabbit corneas (n=6). Infected eyes were graded by slit-lamp examination (SLE) at 20, 24, 28, and 32 hr postinfection (PI). Rabbits were sacrificed at 33 hr PI, and the log CFU (+/-SEM) per cornea was determined. RESULTS: SLE scores for eyes infected with P. putida producing elastase were significantly higher than those infected with vector alone at all time points (por=0.1), but small erosions formed in 33% of corneas. At both 24 and 28 hr PI, the SLE scores for corneas infected with P. putida producing elastase were significantly higher than those infected with P. putida producing alkaline protease (p相似文献   

Measurement systems in principle and in practice: the example of nursing workload

There has been a rapid development of measurement systems in the health services in the United Kingdom (UK) over recent years, not always matched by a thorough understanding of the phenomenon being measured and rarely based on any assessment of reliability or validity A particularly flagrant example of this process is the development of nursing workload measurement systems (NWMS) The estimates from four NWMS were examined They were substantially different from each other for no obvious reason, and the difference between any of the estimates and the actual nursing hours worked could not be explained in terms of any other aspect of the nursing process There is no evidence that the NWMS deployed in the UK are anything more than an expensive numbers game, without this kind of investigation of how they actually work in practice , it would be prudent to be wary about any of the measurement systems which have been proposed Yet many of the measurement systems used in other sectors of the health service are equally untested