Biomedical subjects

Joanna Jaworska

Publications and source records attributed to Joanna Jaworska.

8 recordsLinked to original sources

PubMed2006

Toll-like receptors--novel targets in allergic airway disease (probiotics, friends and relatives).

Experimental and epidemiological studies enabled to hypothesize that stimulation of the immune system by selected microbial products may prevent or treat allergic diseases. According to recent advances in molecular immunology, this stimulation acts via group of conserved receptors present on antigen presenting cells, known as toll-like receptors (TLRs). These receptors play an essential role in antigen presentation and latter development of immune response into pro-allergic (Th2), cellular (Th1) or regulatory (Tr1) responses. Since toll-like receptors govern decisive points in immune regulation, an extensive research focuses on agents interfering with their immunomodulatory activities. In this report, we review information on the potential use of microbial products in allergy prevention and therapy, which are believed to target toll-like receptor network. Current toll-like receptor-based approaches, as well as potential use of lipopolysaccharide (and derivates), oligonucleotides, mycobacteria, bacterial extracts, and probiotics are discussed herein.

Animals↗

PubMed2005

QSAR applicabilty domain estimation by projection of the training set descriptor space: a review.

As the use of Quantitative Structure Activity Relationship (QSAR) models for chemical management increases, the reliability of the predictions from such models is a matter of growing concern. The OECD QSAR Validation Principles recommend that a model should be used within its applicability domain (AD). The Setubal Workshop report provided conceptual guidance on defining a (Q)SAR AD, but it is difficult to use directly. The practical application of the AD concept requires an operational definition that permits the design of an automatic (computerised), quantitative procedure to determine a models AD. An attempt is made to address this need, and methods and criteria for estimating AD through training set interpolation in descriptor space are reviewed. It is proposed that response space should be included in the training set representation. Thus, training set chemicals are points in n-dimensional descriptor space and m-dimensional model response space. Four major approaches for estimating interpolation regions in a multivariate space are reviewed and compared: range, distance, geometrical, and probability density distribution.

Amines↗

PubMed2005

An approach to determining applicability domains for QSAR group contribution models: an analysis of SRC KOWWIN.

QSAR model predictions are most reliable if they come from the models applicability domain. The Setubal Workshop report provides a conceptual guidance for defining a (Q)SAR applicability domain. However, an operational definition is necessary for applying this guidance in practice. It should also permit the design of an automatic (computerised) procedure for determining a models applicability domain. This paper attempts to address this need for models that use a large number of descriptors (for example, group contribution-based models). The high dimensionality of these models imposes specific computational restrictions on estimating the interpolation region. The Syracuse Research Corporation KOWWIN model for prediction of the n-octanol/water partition coefficient is analysed as a case study. This is a linear regression model that uses 508 fragment counts and correction factors as descriptors, and is based on the group contribution approach. We conclude that the applicability domain estimation by descriptor ranges, combined with Principal Component rotation as a data pre-processing step, is an acceptable compromise between estimation accuracy and the amount of data in the training set.

Computer Simulation↗

PubMed2005

Influence of polymorphisms in DNA repair genes XPD, XRCC1 and MGMT on DNA damage induced by gamma radiation and its repair in lymphocytes in vitro.

DNA single-strand breaks (SSBs) were quantified by single-cell gel electrophoresis and micronucleated and apoptotic cells were quantified by microscopic assays in peripheral blood lymphocytes after irradiation on ice with 2 Gy of 60Co gamma radiation, and their association with polymorphisms of genes that encode proteins of different DNA repair pathways and influence cancer risk (XPD codon 312Asp --> Asn and 751Lys --> Gln, XRCC1 399Arg --> Gln, and MGMT 84Leu --> Phe) was studied. In unirradiated lymphocytes, SSBs were significantly more frequent in individuals older than the median age (52 years) (P = 0.015; n = 81), and the frequency of apoptotic or micronucleated cells was higher in individuals with alleles coding for Asn at XPD 312 or Gln at 751 (P = 0.030 or 0.023 ANOVA, respectively; n = 54). The only polymorphism associated with the background SSB level was MGMT 84Phe (P = 0.04, ANOVA; n = 66). After irradiation, SSB levels and repair parameters did not differ significantly with age or smoking habit. The SSB level varied more than twofold and the repair rate and level of unrepaired SSBs more than 10-fold between individuals. The presence of variant alleles coding for Asn at XPD 312 was associated with more radiation-induced SSBs (P = 0.014) and fewer unrepaired SSBs (P = 0.008), and the phenotype (> median induced SSBs/< median unrepaired SSBs) was seen in the majority of XPD 312Asn/Asn homozygotes; the odds ratio for variant homozygotes to show this phenotype was 5.2 (95% confidence interval 1.4-19.9). The hypothesis is discussed that XPD could participate in repair of ionizing radiation-induced DNA damage. While it cannot be excluded that the effects observed are due to cosegregating polymorphisms or that the responses of lymphocytes are not typical of other cell types, the results suggest that polymorphism of DNA repair genes, particularly XPD, is one factor implicated in the variability of responses to ionizing radiation between different individuals.

Adult↗

PubMed2003

Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs.

This article provides an overview of methods for reliability assessment of quantitative structure-activity relationship (QSAR) models in the context of regulatory acceptance of human health and environmental QSARs. Useful diagnostic tools and data analytical approaches are highlighted and exemplified. Particular emphasis is given to the question of how to define the applicability borders of a QSAR and how to estimate parameter and prediction uncertainty. The article ends with a discussion regarding QSAR acceptability criteria. This discussion contains a list of recommended acceptability criteria, and we give reference values for important QSAR performance statistics. Finally, we emphasize that rigorous and independent validation of QSARs is an essential step toward their regulatory acceptance and implementation.

Environmental Exposure↗

PubMed2003

Guidelines for developing and using quantitative structure-activity relationships.

Numerous quantitative structure-activity relationships (QSARs) have been developed to predict properties, fate, and effects of mostly discrete organic chemicals. As the demand for different types of regulatory testing increases and the cost of experimental testing escalates, there is a need to evaluate the use of QSARs and provide some guidance to avoid their misuse, especially as QSARs are being considered for regulatory purposes. This paper provides some guidelines that will promote the proper development and use of QSARs. While this paper uses examples of QSARs to predict toxicity, the proposed guidelines are applicable to QSARs used to predict physical or chemical properties, environmental fate, ecological effects and health effects.

Animals↗

PubMed2003

Limitations of current risk characterization methods in probabilistic environmental risk assessment.

In probabilistic environmental risk assessment, the likelihood and the extent of adverse effects occurring in ecological systems because of exposure(s) to substances are estimated. It is based on the comparison of an exposure/environmental concentration distribution, with a species sensitivity distribution derived from toxicity data. The calculation of a probabilistic risk can be performed in many ways (e.g., area under the curve in joint probability curves). However, several (hypothetical) examples and some theoretical considerations illustrate that the current risk characterisation methods have an integrative character and they focus on the statistical comparison of two distributions without properly considering the environmental interpretation of these underlying distributions. Several scenarios with varying exposure/environmental concentration distribution and species sensitivity distribution standard deviations are discussed.

Animals↗

PubMed2002

Environmental risk assessment of phosphonates, used in domestic laundry and cleaning agents in The Netherlands.

In the long-term cooperative project Voluntary Plan of Action (1990) between the Dutch Soap and Detergent Association (NVZ) and the Dutch Ministry of Housing, Spatial Planning and the Environment (VROM) environmental risk assessments of several main components of laundry cleaning formulations were completed. As a part of that project the environmental risk assessment of HEDP, ATMP, EDTMP and DTPMP phosphonates used in detergent applications has been carried out according to the EU Technical Guidance Document for Environmental Risk Assessment for New and Existing Chemicals. All PEC/PNEC ratios were well below 1. Results of this assessment based on the total industry volumes from 1995 and 1998 indicate that the environmental risk of these phosphonates is low in The Netherlands with properly functioning sewage treatment plants.

Chelating Agents↗