Increased variability in Apc(Min)/+ intestinal tissue can be measured with microultrasound.

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic.

Combined changes in Wnt signaling response and contact inhibition induce altered proliferation in radiation-treated intestinal crypts.

Curative intervention is possible if colorectal cancer is identified early, underscoring the need to detect the earliest stages of malignant transformation. A candidate biomarker is the expanded proliferative zone observed in crypts before adenoma formation, also found in irradiated crypts. However, the underlying driving mechanism for this is not known. Wnt signaling is a key regulator of proliferation, and elevated Wnt signaling is implicated in cancer. Nonetheless, how cells differentiate Wnt signals of varying strengths is not understood. We use computational modeling to compare alternative hypotheses about how Wnt signaling and contact inhibition affect proliferation. Direct comparison of simulations with published experimental data revealed that the model that best reproduces proliferation patterns in normal crypts stipulates that proliferative fate and cell cycle duration are set by the Wnt stimulus experienced at birth. The model also showed that the broadened proliferation zone induced by tumorigenic radiation can be attributed to cells responding to lower Wnt concentrations and dividing at smaller volumes. Application of the model to data from irradiated crypts after an extended recovery period permitted deductions about the extent of the initial insult. Application of computational modeling to experimental data revealed how mechanisms that control cell dynamics are altered at the earliest stages of carcinogenesis.

Preparation of wholemount mouse intestine for high-resolution three-dimensional imaging using two-photon microscopy.

Visualizing overall tissue architecture in three dimensions is fundamental for validating and integrating biochemical, cell biological and visual data from less complex systems such as cultured cells. Here, we describe a method to generate high-resolution three-dimensional image data of intact mouse gut tissue. Regions of highest interest lie between 50 and 200 mum within this tissue. The quality and usefulness of three-dimensional image data of tissue with such depth is limited owing to problems associated with scattered light, photobleaching and spherical aberration. Furthermore, the highest-quality oil-immersion lenses are designed to work at a maximum distance of

Stress and avoidance in Pseudoseizures: testing the assumptions.

Twenty women and 10 men with Pseudoseizures were matched by age and gender with an epilepsy- and a healthy-control group. In response to clinical and research evidence of a relationship between Pseudoseizures and the experience of stress, it was hypothesised that people with Pseudoseizures would perceive their ongoing lives as more stressful, and use more avoidant and distancing coping, and less problem-focused coping, than people in the two control groups. Using the Perceived Stress Scale (Cohen et al., J. Health Soc. Behav. 24, 1983, 385-396) and the Ways of Coping, revised version (Folkman and Lazarus, Manual for Ways of Coping Questionnaire, Consulting Psychologist Press, Paola Alto, CA, 1988) the study found that people with Pseudoseizures: (1) perceived their ongoing lives as significantly more stressful; (2) were significantly more likely to use a maladaptive (escape-avoidant) coping strategy; and (3) were significantly less likely to use an adaptive (planful problem solving) approach to coping than healthy controls. The study findings indicate that people with Pseudoseizures experience lives as stressful as do people with epilepsy, and are likely to employ maladaptive coping responses. Implications for diagnosis, intervention and future research are discussed.

In vitro cultivation and developmental cycle in culture of a parasitic dinoflagellate (Hematodinium sp.) associated with mortality of the Norway lobster (Nephrops norvegicus) in British waters.

Dinoflagellates are common and often important parasites of aquatic organisms, but their developmental cycles are poorly known and have not been established in in vitro culture. The parasitic dinoflagellate (Hematodinium sp.) associated with mortality of the Norway lobster (Nephrops norvegicus) in British waters has been cultivated in vitro in 10% foetal calf serum in a balanced Nephrops saline. In culture the parasite undergoes a characteristic cycle of development. Circulating sporoblasts from the host's haemolymph in vitro generate 2 kinds of flagellated uninucleate dinospore, macrospores and microspores, either of which will, after 5 weeks in fresh medium, germinate to produce multinucleate unattached filamentous trophonts. These trophonts multiply by fragmentation and growth and may be serially subcultured in this form, at 2 week intervals, indefinitely. If not subcultured, the filamentous trophonts give rise to colonies of radiating filaments ('gorgonlocks') which subsequently attach to the substratum to form flattened web-like 'arachnoid' multinucleate trophonts. Arachnoid trophonts become arachnoid sporonts when they synthesize trichocysts and flagellar hairs and may give rise to secondary arachnoid sporonts or to dinospores which initiate a new cycle.

Beyond child development centres: care coordination for children with disabilities.

A specific model of care coordination for children with disabilities is described, comprising parental empowerment, a defined client population, individual tailoring of service based on assessment of need, inter-agency collaboration beyond existing team boundaries, continuity of named professional contact across transitions important to families, and a named care coordinator. The first stages of local implementation of the model are described for children with a disability making the transition into nursery school provision. Qualitative findings from interviews with families and care coordinators are presented, and the possibility of care coordinators providing a Named Person function is examined.

Depressive symptoms and self-concept in young people with spina bifida.

Examined self-reported depressive symptoms in 72 young people with spina bifida, ages 9 to 18:11, and matched able-bodied comparison subjects, using the Dimensions of Depression Profile for Children and Adolescents (Harter & Nowakowski, 1987). Independent variables included gender, self-perceptions (including physical appearance), and perceived social support. Young people with spina bifida were at greater risk of depressive mood, low self-worth, and suicidal ideation. Girls, independent of disability, were at greater risk of depressive mood, low self-worth, and self-blame. Multiple regression analyses suggest that global self-worth serves as a mediating variable for the effect of physical appearance self-concept on depressed mood (particularly in young people with spina bifida), and that perceived parental social support has a direct effect on depressed mood (particularly in girls).

Presence of apicomplexan-type micropores in a parasitic dinoflagellate, Hematodinium sp.

Structures resembling apicomplexan micropores were found by transmission electron microscopy in in vitro-cultured and in in vivo forms of the parasitic dinoflagellate Hematodinium sp. from crustacean hosts. Uptake of colloidal gold indicated a cytostomal function for the micropores.

Impact of functional severity on self concept in young people with spina bifida.

This study examines the relationship between medical and functional severity of disability and levels of self esteem and self concept in 79 young people with spina bifida. Greater feelings of global self worth and of self esteem in physical appearance were associated with greater severity of disability. This was only in part an effect of lower IQ among the most disabled young people. Many of the least disabled had marked impairment of self esteem. Analysis of the impact of individual aspects of disability confirmed the association between increased self esteem in physical appearance and global self worth, and diminished functional ability. Academic self ratings, however, were higher in the less disabled. Hydrocephalus and continence appeared to have minimal effect on self esteem. The relationship between severity of disability in spina bifida and self concept is complex and mediated by a range of factors. It is incorrect to assume that the psychological impact is less in the mildly disabled young person.

The self-concept of young people with spina bifida: a population-based study.

Seventy-nine young people with spina bifida were given a psychological, medical, carer and occupational therapy assessment. 79 matched able-bodied young people received the psychosocial interview. The disabled group felt themselves to be less competent in academic, athletic and social aspects of self-concept, less supported by classmates, equally supported by parents and friends and more supported by teachers than the able-bodied group. Disabled subjects did not discount the importance of any area of personal-social functioning, and experienced greater discrepancies between competence and importance in most academic, athletic, social and physical appearance aspects of self-concept. Disabled girls assigned very high importance to physical appearance. Physical appearance was more strongly associated with general self-esteem than any other area of self-concept.

Models of parent partnership and child development centres.

Four models (and an emergent fifth model) of parent partnership are described and their relevance to UK child development centres is explored. Clinical, management and service development issues are drawn out.