Toxoplasma gondii: characterization of a mutant resistant to 6-thioxanthine

6-Thioxanthine caused 50% inhibition of the growth of Toxoplasma gondii in human fibroblasts at a concentration of 5 micrograms/ml. A mutant induced by treatment with ethylnitrosourea (ThxR-1) was 20-fold more resistant than the wildtype. Wild-type parasites grown in Lesch-Nyhan fibroblasts efficiently incorporated hypoxanthine, guanine, and xanthine, but ThxR-1 incorporated each of these precursors less than 2% as well as the wildtype did. Soluble extracts of wild-type parasites had potent phosphoribosyltransferase activities for hypoxanthine, guanine, and xanthine, while extracts of ThxR-1 had barely detectable activity with any of these substrates. The basis for the resistance of ThxR-1 to 6-thioxanthine is, therefore, the lack of the enzyme hypoxanthine-guanine phosphoribosyltransferase. Thus, salvage pathways that employ this enzyme are not essential for the acquisition of purines, which the parasite must obtain from the host cell. Incubation in a medium containing mycophenolic acid and xanthine allowed the efficient recovery of wild-type T. gondii in the presence of many ThxR-1 parasites. Together with the use of 6-thioxanthine to detect resistant mutants in the presence of many wild-type parasites, this procedure provides a simple selection and back-selection for mutations that affect the hypoxanthine-guanine phosphoribosyltransferase gene of T. gondii.     

Exploratory research: a methodological procedure for the study of human factors in the field of Public Health

Exploratory research is proposed as a methodological procedure for a qualitative approach. The main purpose of this procedure is that of helping the researcher to develop a measurement tool which reflects reality. Both exploratory research conceptions, the traditional and the new one are discussed. The application of this methodological procedure to the study of human factors is recommended and the implementation stages are presented. Some applications for research in public health are suggested.     

Assessing health-related quality of life in chronic hepatitis C using the Sickness Impact Profile

In a randomized, controlled trial that demonstrated the efficacy of interferon alfa-2b 3 million units three times a week for 24 weeks in controlling chronic hepatitic C (non-A, non-B), the Sickness Impact Profile (SIP) was used to evaluate the impact of disease and treatment on health-related quality of life (HRQOL). The SIP was self-administered by 160 patients before treatment, at the end of treatment, and at the study endpoint. Before treatment, patients with chronic hepatitis C scored significantly (P < 0.05) higher (worse) than an historical control group of the general population in mean total SIP score and in all categories except eating. The highest degree of impairment was observed in the work, sleep and rest, and recreation and pastimes categories. After treatment, patients who received interferon alfa-2b had significant (P < or = 0.05) improvement in work, sleep and rest, and recreation and pastimes scores. Numerical improvement was observed in total score, physical and psychosocial dimension scores, and most individual category scores. Mean SIP scores were unchanged or slightly worsened in untreated control patients. In responders (patients with improvement in serum alanine aminotransferase levels), the largest improvement was seen in work scores. The SIP appears to be a reliable and valid instrument for describing the impact of chronic hepatitis C on HRQOL but lacks disease-specificity and the ability to reflect clinically relevant changes. Thus the SIP is not the best instrument to evaluate the HRQOL effects of treatment with interferon alfa-2b in patients with chronic hepatitis C.     

The morphology of identified neurons in the abdominal ganglion of Aplysia californica

The morphology of identified neurons and of one multiaction interneuron (L10) of the abdominal ganglion of Aplysia has been studied using cobalt chloride, injected intracellularly. Cells with little synaptic input, R3-R14, had a relatively poorly developed dendritic tree, whereas the dendrite tree of cells L7 and L10, with extensive synaptic input, was highly complex. Cells L1-L6 and the RB cell cluster were found to have intermediate complexity of synaptic inputs and dendritic morphology. Within cell clusters, individual cells were often morphologically distinct. Identified cells have both invariant and variant axonal branches. Variant axons often project down other than their customary nerve trunks or are supernumerary. Three features of neuropil architecture were encountered. (1) When cells from the same cluster send their axons down the same nerve the axons often run in fascicles. (2) Although an identified cell's dendritic geometry varies from preparation to preparation, its dendrites always occupy approximately the same position in the neuropil. (3) The postsynaptic follower cells of L10 send their main axons through the axonal arborization of L10.     

Immediate colour constancy

Colour constancy is traditionally interpreted as the stable appearance of the colour of a surface despite changes in the spectral composition of the illumination. When colour constancy has been assessed quantitatively, however, by observers making matches between surfaces illuminated by different sources, its completeness has been found to be poor. An alternative operational approach to colour constancy may be taken which concentrates instead on detecting the underlying chromatic relationship between the parts of a surface under changes in the illuminant. Experimentally the observer's task was to determine whether a change in the appearance of a surface was due to a change in its reflecting properties or to a change in the incident light. Observers viewed computer simulations of a row of three Mondrian patterns of Munsell chips. The centre pattern was a reference pattern illuminated by a simulated, spatially uniform daylight; one of the outer patterns was identical but illuminated by a different daylight; and the other outer pattern was equivalent but not obtainable from the centre pattern by such a change in illuminant. Different patterns and different shifts in daylight were generated in each experimental trial. The task of the observer was to identify which of the outer patterns was the result of an illuminant change. Observers made reliable discriminations of the patterns with displays of durations from several seconds to less than 200 ms, and, for one observer, with displays of 1 ms. By these measures, human observers appear capable of colour constancy that is extremely rapid, and probably preattentive in origin.