Toxicity characterization of complex mixtures using biological and chemical analysis in preparation for assessment of mixture similarity

In the United States, several proposed approaches for using bioassays for the risk assessment of complex hazardous mixtures require that selected mixtures be "sufficiently similar" to each other. The goal of this research was to evaluate the utility of a protocol using in vitro bioassays and chemical analysis as a basis for assessing mixture similarity. Two wood preserving wastes (WPWs) containing polycyclic aromatic hydrocarbons and pentachlorophenol were extracted and fractionated to generate potentially similar mixtures. Chemical analysis was conducted using gas chromatography/mass spectrometry. Genotoxicity was evaluated using the Salmonella/microsome and Escherichia coli prophage induction assays. The crude extract of one WPW was also tested in the chick embryotoxicity screening test (CHEST) assay. The CHEST assay provided the most sensitive measurement of toxicity. Overall, the biological potency of the samples was not well correlated with predicted potency based on chemical analysis. Although several mixtures appeared similar based on chemical analysis, the magnitude of the response in bioassays was often dissimilar. Fractionation was required to detect the genotoxicity of mixture components in vitro. The results confirm the need for an integrated protocol, combining chemical analysis, fractionation, and biological testing to characterize the risk associated with complex mixtures.     

Thinking about Antarctic Heritage: kaleidoscopes and filters

The preliminary results of a project that is currently investigating the nature and range of meanings of Antarctic heritage are explored. The project involves two visits to Scott Base, and the subjects of the qualitative research are the members of the New Zealand Antarctic community. Work so far suggests that different meanings do exist, and a four-fold typology of meanings is suggested which needs to be considered in decisions affecting the future of Antarctica.     

Partial characterization of an immortalized human trophoblast cell-line, TCL-1, which possesses a CSF-1 autocrine loop

High doses of morphine produce a state of behavioural inactivity and muscular rigidity. This type of 'catalepsy' is clearly different from the state which is produced by the administration of neuroleptics, e.g. haloperidol. While haloperidol-induced catalepsy can easily be antagonised by NMDA receptor antagonists, there has been a report that the non-competitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK-801) potentiates morphine-induced catalepsy. The aim of this study was to further examine the role of glutamate receptors in the mediation of morphine-induced catalepsy. To this end we coadministered morphine (20, 40, 60 mg/kg i.p.) with MK-801 (0.1 and 0.3 mg/kg i.p.), the competitive NMDA receptor antagonist DL-(E)-2-amino-4-methyl-5-phosphono-3-pentoic acid (CGP 37849) (2 and 6 mg/kg i.p.), or 1-(4-aminophenyl)-4-methyl-7,8-methylen-dioxy-5H-2,3- benzodiazepine (GYKI 52466) (2 and 4 mg/kg), an antagonist of the AMPA type of glutamate receptors, respectively. The degree of catalepsy was assessed using two different methods, the 'bar/podium/grid' test which is commonly used to measure neuroleptic-induced catalepsy, and a test for the presence or absence of righting reflexes after turning the animals into a supine position. It was found that in the 'bar/podium/grid' test coadministration of both NMDA receptor antagonists significantly and dose-dependently augmented morphine-induced catalepsy. The results using the AMPA receptor antagonist were less clear since the lower dose of GYKI 52466 tended to attenuate the morphine effect whereas the higher dose augmented morphine-induced catalepsy in some cases. While placing the animals on the bar and on the podium produced essentially the same results, the grid was found to be inapplicable for the measurement of morphine-induced catalepsy since the animals did not cling to the grid and fell off almost immediately after being released from the experimenter's hand. With respect to the righting reflexes it was found that the number of animals not showing these responses increased when MK-801 or CGP 37849 was coadministered with morphine. In contrast, most of the animals treated with GYKI 52466 and morphine displayed intact righting reflexes. It is concluded that glutamatergic transmission plays an important role in the mediation of morphine-induced catalepsy, though different to that of haloperidol-induced catalepsy, and that NMDA and AMPA receptors are differentially involved in different aspects of the associated behavioural state.     

Primary binding domain of bovine von Willebrand factor fragment expressed in E. coli

Bovine vWF cDNA has been cloned from a bovine endothelial cell library. A fragment of this cDNA, corresponding to amino acid sequence Leu 469-Ser 723, called primary adhesion domain (PAD-1), and containing the binding sites for platelet glycoprotein Ib (GPIb), heparin and collagen, has been expressed in E. coli. The reduced and alkylated form of fragment PAD-1 inhibited native vWF binding to GPIb. Fragment PAD-1 bound to heparin and botrocetin in a specific and dose dependent manner as did the native vWF. In a solid-phase assay, fragment PAD-1 bound to calf skin collagen in contrast to a human vWF recombinant fragment (Ser 445-Val 733) which was inactive in the same assay. The studies presented in this paper demonstrated that the A1 domain of bovine vWF contained the GPIb, heparin, botrocetin as well as collagen binding sites and that integrity of the disulfide bond (Cys 509-Cys 695), did not seem to be essential for binding of bovine vWF fragment to GPIb.     

Parenting stress among dual-earner mothers and fathers: Are there gender differences?

Stress in the parenting role has been found to be related to family functioning and parenting behavior. However, most research in this area has been conducted with clinical samples and has not compared parenting stress of mothers and fathers. In this study, 589 married couples with young children (12 to 60 months old) completed the Parenting Stress Index-Short Form (Abidin, 1990) and measures of child-rearing behaviors and attitudes, social support, and child behavior. The validity of Abidin's measure and theoretical model was tested, and results were mixed. Small effects were found for mothers and fathers, and these were moderated by child age and marital happiness. Stress as a normal consequence of parenting is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gram-negative anaerobic bacilli: Their role in infection and patterns of susceptibility to antimicrobial agents. II. Little-known Fusobacterium species and miscellaneous genera

Twenty infrequently reported species of gram-negative anaerobic bacilli other than Fusobacterium nucleatum, Fusobacterium necrophorum, and members of the genus Bacteroides were studied with regard to their role in infection and their susceptibility to antimicrobial agents. In addition, the literature regarding the recovery of these organisms from both the normal flora and infections of humans was reviewed. During a six-year period at the Wadsworth Clinical Anaerobic Bacteriology Research Laboratory (Veterans Administration Wadsworth Medical Center, Los Angeles, Calif.), 39 (6%) of 679 specimens obtained from anaerobic infections yielded "other gram-negative anaerobic bacilli" (OGNAB). Fusobacterium naviforme, Fusobacterium gonidiaformans, Fusobacterium varium, Fusobacterium mortiferum, and Fusobacterium russii were the most commonly isolated OGNAB. Most of the OGNAB tested were resistant to erythromycin, and most strains, except for F. varium, were susceptible to beta-lactam antibiotics and clindamycin. Chloramphenicol and metronidazole were active against all strains of OGNAB tested. Certain Fusobacterium species are undoubtedly previously unrecognized members of the normal flora of the oropharynx, upper respiratory tract, or urogenital tract and may be present in infections derived from these floras.     

Clinical applications of composite and realtime megavoltage imaging

The versatility of electronic portal imaging devices (EPIDs) is best demonstrated by their ability to perform novel megavoltage imaging protocols, which are still pertinent to good radiotherapy practice. This paper examines two such techniques: composite and realtime imaging. Our EPID can be programmed to acquire and manipulate images very easily, allowing images from segmented treatment protocols to be mixed and displayed, giving a composite image of the effective treatment result. Its use for verifying the efficacy of spinal shielding using a segmented, offset collimator technique is described. By acquiring images very quickly, realtime imaging sequences can be obtained and used to analyse anatomical movement within a single treatment field. The technique is employed here to investigate movement in radical lung, breast, abdomen, pelvis and thyroid treatments. Our results show that the protocol is vital for treatment sites involving the lungs; changes up to 5 mm have been observed in the maximum lung depth for breast treatments, and displacements up to 16 mm for radical lung treatments. It is also useful in other anatomical sites for ensuring that no movement occurs.