The structure of mother-child play: young children with Down syndrome and typically developing children.

This study explored developmental changes and effects of Down syndrome on mothers' structuring of their children's play. Mothers and their young children with Down syndrome (n = 28) were compared with socioeconomically matched samples of mothers and their mental age-matched (n = 28) and chronological age-matched (n = 28) typically developing children. Mothers of typically developing children exhibited more object demonstrations with their developmentally younger children, who exhibited less object play.

Use of reversed-phase high-performance liquid chromatography on polystyrene-divinylbenzene columns for the rapid separation and purification of acid-soluble nuclear proteins.

The suitability of polystyrene-divinylbenzene reversed-phase HPLC columns for rapid separation and purification of acid-soluble nuclear proteins was evaluated. We used a polystyrene-divinylbenzene reversed-phase HPLC column (PLRP-S) for purification of nuclear proteins extracted with 0.3 M HCl or 5% HClO4.

QSARS for the eye irritation potential of neutral organic chemicals.

A quantitative structure-activity relationship (QSAR) was derived previously relating European Community (EC) eye irritation classification data of a set of neutral organic chemicals, to log(octanol/water partition coefficient), to the minor principal inertial axes (Ry and Rz) and to dipole moment. Eye irritation scores on a scale of 1-10 for a set of aliphatic alcohols (from the work of Smyth and Carpenter) have been shown to correlate well with the same four physicochemical parameters by means of neural network analysis. The original classification dataset of neutral organic chemicals has been augmented by the addition of a number of the aliphatic alcohols from the Smyth and Carpenter data that could unequivocally be assigned the EC classifications of irritant (those with eye irritation scores of 8 and 9) or non-irritant (scores of 1).

p38/RK is essential for stress-induced nuclear responses: JNK/SAPKs and c-Jun/ATF-2 phosphorylation are insufficient.

The ERK, JNK/SAPK and p38/RK MAP kinase subtypes (reviewed in [1]) are differentially activated in mammalian cells by various stimuli, which elicit induction of immediate-early (IE) genes, such as c-fos and c-jun (reviewed in [1-3]), as well as phosphorylation of histone H3 [4] and HMG-14 [5]. Anisomycin and UV radiation have been suggested to induce c-fos and c-jun transcription via JNK/SAPK-mediated phosphorylation of TCF (ternary complex factor), for c-fos induction [6-8], and c-Jun and/or ATF-2 for c-jun induction [9-11] [12,13]. We report here that anisomycin and ultraviolet radiation (UV) activate MAP kinase kinase-6 (MKK6) [14,15], p38/RK [16] [17,18] and MAPKAP kinase-2 (MAPKAP K-2) [17-19].

The use of in vitro cytotoxicity measurements in QSAR methods for the prediction of the skin corrosivity potential of acids.

Quantitative structure-activity relationships (QSAR) methods have been derived that relate the severity of skin corrosivity (designated by the EC risk phrases R34 and R35) of acids to parameters that model their skin permeability and cytotoxicity. Skin permeability was modelled by log(octanol/water partition coefficient), molecular volume and melting point, while the cytotoxicity of the acids was accounted for by their pK(a), values and the in vitro cytotoxicity of their sodium salts towards Swiss mouse embryo 3T3 cells. The dataset was analysed using principal components and neural network analysis.

Quantitative structure-Activity relationships for skin irritation and corrosivity of neutral and electrophilic organic chemicals.

Quantitative structure-activity relationships (QSARs) have been derived by relating skin irritation and corrosivity data of neutral and electrophilic organic chemicals to their log(octanol/water partition coefficient) (logP), molecular volume, dipole moment and 1/molecular weight. Datasets were analysed using stepwise regression, discriminant and principal components analysis. Discriminant analysis between irritant and non-irritant neutral and electrophilic organic chemicals using the above parameters, which broadly model skin permeability (logP and molecular volume), 'reactivity' (dipole moment) and l/molecular weight to compensate for the fact that skin irritation/corrosivity testing is carried out using a fixed mass or volume of chemical, was found to discriminate well for only 73.

In vitro investigations of the direct effects of complex anions on thyroidal iodide uptake: Identification of novel inhibitors.

Iodide uptake (IU) by thyrocytes from the plasma against chemical and electrical gradients is by a specific iodide transporter or 'pump'. Perchlorate (ClO(4)(-)) and other univalent, symmetrical anions are competitive inhibitors of iodide uptake (IU), and apparent K(i) for individual anions can be correlated with ion size. This study uses cultured thyrocytes and a broad range of anion size, in particular a series of spherical hexafluoride ions, in order to understand more about the parameters governing the activity of competitive inhibitors of IU.

Skin corrosivity potential of fatty acids: In vitro rat and human skin testing and QSAR studies.

The corrosive potential of a series of fatty acids-propanoic acid (C3), butanoic acid (C4), hexanoic acid (C6), octanoic acid (C8), decanoic acid (C10) and dodecanoic acid (C12)-was investigated in the in vitro skin corrosivity test (IVSCT) using both rat skin and human skin. All the fatty acids with alkyl chain lengths up to and including C8 were found to be corrosive to rat skin. When human skin was used, the corrosive/non-corrosive threshold was shifted to around the C6 fatty acid.

Quantitative structure-activity relationships (QSARs) for skin corrosivity of organic acids, bases and phenols: Principal components and neural network analysis of extended datasets.

Quantitative structure-activity relationships (QSARs) relating skin corrosivity data of organic acids, bases and phenols to their log(octanol/water partition coefficient), molecular volume, melting point and pK(a). have been extended to substantially larger datasets. In addition to principal components analysis, as used in earlier work, the datasets have also been analysed using neural networks.

Computer prediction of possible toxic action from chemical structure: an update on the DEREK system.

Computer-based assessment of potential toxicity has become increasingly popular in recent years. The knowledge-base system DEREK is developed under the guidance of a multinational Collaborative Group of expert toxicologists and provides a qualitative approach to toxicity prediction. Major developments of the DEREK program and knowledge-base have taken place in the last 3 years.

An alternative strategy to the use of guinea pigs for the identification of skin sensitization hazard.

For over half a century, guinea pig methods have dominated the field of toxicology concerned with the identification of skin sensitizers. Specific protocols, for example the guinea pig maximization test (GPMT), have been pre-eminent in the identification of skin sensitization hazard for regulatory purposes. However, there are increasingly several forces driving change, not least animal use/welfare considerations.

A quantitative structure-activity relationship for the eye irritation potential of neutral organic chemicals.

Quantitative structure-activity relationships (QSARs) have been derived relating eye irritation data of a set of neutral organic chemicals to log(octanol-water partition coefficient), the minor principal inertial axes (Ry and Rz) and dipole moment. Datasets were analysed using principal components analysis; plots of the first 2 principal components of the above parameters showed that the analysis was able to discriminate well between the irritant and non-irritant chemicals in the dataset. The derived QSAR could be useful for the prediction of the eye irritation potential of new or untested chemicals within this category.

Practical applications of QSAR to in vitro toxicology illustrated by consideration of eye irritation.

Mechanistically based quantitative structure-activity relationships (QSARs) have been developed for some well defined toxic endpoints. Principal components analysis has proved to be a useful technique in visualizing the QSARs and allows ready construction of hypotheses to test. The preferred way of testing the hypotheses is to use in vitro methods: thus integrating the use of QSAR and in vitro methods.

Quantitative structure-activity relationships for skin permeability.

In vitro human skin permeability coefficient data collected by Flynn (1990) have been analysed using multiple regression analysis. An improved model for the prediction of permeability coefficients has been derived by the inclusion of the melting point as an independent variable in addition to the octanol-water partition coefficient (as logP) and molecular volume. (The solubility of chemicals in water is related to logP and melting point through an algorithm; Suzuki, Journal of Computer-Aided Molecular Design 1991, 5, 149-166.

Quantitative structure activity relationships for skin corrosivity of organic acids, bases and phenols.

Quantitative structure activity relationships (QSARs) have been derived relating skin corrosivity data of organic acids, bases and phenols to their log(octanol/water partition coefficient), molecular volume, melting point and pKa. Datasets were analysed using principal components analysis; plots of the first 2 principal components of the above parameters, which broadly model skin permeability and cytotoxicity, for each group of chemicals showed that the analysis was able to discriminate well between corrosive and non-corrosive chemicals. The derived QSARs should be useful for the prediction of the skin corrosivity potential of new or untested chemicals.

A mitogen- and anisomycin-stimulated kinase phosphorylates HMG-14 in its basic amino-terminal domain in vivo and on isolated mononucleosomes.

The rapid, transient induction of 80-100 immediate-early (IE) genes upon mitogenic stimulation occurs irrespective of protein synthesis and is mediated by modification of existing proteins. Two mechanisms, not mutually exclusive, involving modification either of sequence-specific transcription factors or of structural chromatin proteins primed by pre-association with responsive effectors are conceivable. Here, we show that upon IE gene induction, the non-histone high-mobility-group protein HMG-14, but not the related protein HMG-17, becomes serine phosphorylated in its basic, amino-terminal region close to where it binds nucleosomal DNA.

An expert system rulebase for identifying contact allergens.

There are currently no in vitro methods suitable for the prospective identification of skin sensitizers (contact allergens). Knowledge relating chemical structure to toxicity can be programmed into expert systems. An historical database, containing results of 294 defined single substances tested in the guinea pig maximization test (GPMT) carried out according to a single protocol, has been used to derive a set of structural alerts for skin sensitization.

A Quantitative Structure-Activity Relationship (QSAR) for prediction of alpha(2mu)-globulin nephropathy.

A number of chemicals induce a toxic syndrome in male rats-referred to as alpha(2mu)-globulin nephropathy-that is characterized by an accumulation of the urinary protein alpha(2mu)-globulin in renal lysosomes, subsequent cytotoxicity and cell death. Binding affinity to alpha(2mu)-globulin has been identified as one of the determinants for alpha(2mu)-globulin nephropathy. A quantitative structure-activity relationship (QSAR) has been derived by multiple regression analysis relating this binding to negative charge density of the binding molecule and its molecular volume.

Development of an expert system rulebase for identifying contact allergens.

There are currently no in vitro methods for the identification of skin sensitizers (contact allergens). Knowledge relating chemical structure to toxicity can be programmed into expert systems. An historical database containing results of 294 defined single substances tested in the guinea pig maximization test to a single protocol has been used to derive a set of structural alerts for skin sensitization.

Skin sensitization structure-activity relationships for phenyl benzoates.

The key to determining whether a chemical has the ability to behave as a contact allergen must reside ultimately in the structure and properties of that chemical rather than in the immune system. Quantitative structure-activity relationships (QSARs) have been demonstrated for a small number of series of chemicals in the past, using the relative alkylation index model based on this principle. In the present work, a carefully chosen range of phenyl benzoate esters has been synthesized such that they would have a single mechanism of action but otherwise would span important areas of parameter space-reactivity, skin penetration characteristics and biological response.

Mitogen-stimulated phosphorylation of histone H3 is targeted to a small hyperacetylation-sensitive fraction.

Diverse agents, including growth factors and phorbol esters, induce rapid transcriptional activation of a subset of immediate-early (IE) genes that include the protooncogenes c-fos and c-jun. Among the earliest nuclear signaling events concomitant with IE gene activation is the phosphorylation of nucleosomal histone H3 in its basically charged N-terminal tail. This highly conserved domain is also subject to reversible posttranslational acetylation at specific lysine residues, a process implicated in transcriptional regulation.

Cognitive development of preterm low birth weight children at 5 to 8 years old.

Prematurity and low birth weight have been considered to be important risk factors for cognitive development during early childhood; however, it has been suggested that the developmental delays disappear with age. Eighty-one preterm (< 38 weeks) low birth weight (< 2500 g) children between 5 and 8 years old from the Children of the National Longitudinal Survey of Youth were compared with individually matched full-term normal birth weight children to investigate the catch-up delays in cognitive functioning including language and mathematics skills. Preterm children showed a significant delay in cognitive functioning only until 6 years old.

Early channels of mother-infant communication: preterm and term infants.

The impact of prematurity on the responsiveness of mothers and their 4-month-old infants was examined across three channels of communication: attentional, vocal and affective. Log-linear models were used to determine how the behavior of one partner was conditional upon the behavior of the other during home observations of 24 preterm and 24 term infants and their mothers. Visual attention was elicited by vocalization, and the onset of infant gaze was marked by a maternal smile.