Abstract. wingless, the Drosophila homologue of the proto-oncogene Wnt-1, encodes a secreted glycoprotein that regulates differentiation and proliferation of nearby cells. Here we report on the biochemical mechanism(s) by which the wingless signal is transmitted from cell to cell. When expressed in $2 cells, the majority (~83%) of secreted wingless protein (WG) is bound to the cell surface and extracellular matrix through specific, noncovalent interactions. The tethered WG can be released by addition of exogenous heparan sulfate and chondroitin sulfate glycosaminoglycans. WG also binds directly to heparin agarose beads with high affinity. These data suggest that WG can bind to the cell surface via naturally occurring sulfated proteoglycans. Two lines of evidence indicate that extracellular glycosaminoglycans on the receiving cells also play a functional role in WG signaling. First, treatment of WGresponsive cells with glycosaminoglycan lyases reduced WG activity by 50%. Second, when WG-responsive cells were preincubated with 1 mM chlorate, which blocks sulfation, WG activity was inhibited to nearbasal levels. Addition of exogenous heparin to the chlorate-treated cells was able to restore WG activity. Based on these results, we propose that WG belongs to the group of growth factor ligands whose actions are mediated by extracellular proteoglycan molecules.C OMMUNICATION between cells is an integral part of development and differentiation. Cells determine their fates, in part, by where they are located relative to other cells. Work in Drosophila has shown that this positional information is often provided by the distribution of specific extracellular ligands such as the wingless, hedgehog, and decapentaplegic proteins (for reviews see Klingensmith and Nusse, 1994;Siegfried and Perrimon, 1994). Anterior/posterior, dorsal/ventral, and proximal/ distal axes provide the framework for subsequent development of many tissue and organs. Loss of wingless activity alters many of these positional axes, severely disrupting epidermal patterning, appendage formation, and CNS development in Drosophila (Siegfried and Perrimon, 1994).Similar signaling systems are also present in vertebrates.For example, Wnt-1 is required for fetal brain development in mice (McMahon and Bradley, 1990) and body axis specification in Xenopus (McMahon and Moon, 1989). Several lines of evidence indicate that wingless protein (WG) t and Wnt-1 are both structural and functional ho-

Malignant bronchial biopsy samples frequently contain limited amounts of primary carcinoma. Often, one or more of the biopsy fragments will not contain tumor. This has important implications for the storage and use of bronchial biopsy samples for genetic analysis.

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New or adapted methods and tools are needed to ensure the voices of older people with cognitive impairment and dementia are included in evaluations of care services which aim to support their quality of life (QoL). In this study, cognitive interviewing practices were used with a group of 26 older service users with cognitive impairment from two service providers in New South Wales, Australia, to test and modify the Adult Social Care Outcomes Toolkit Easy Read (ER) survey to improve its suitability for this cohort. We used Antonovsky’s “sense of coherence” framework to describe our research approach and how it was adapted to provide a manageable, meaningful, and comprehensible experience for our participants. While the modified ER format made the survey more comprehensible and meaningful, it was the techniques of cognitive interviewing that made the research approach manageable. We argue that while ER does support the research process for older service users with cognitive impairment, combining ER pictorials with the qualitative interactions with the researcher, in particular cognitive interviewing strategies, is needed to support a cohesive approach to assess care-related QoL in this vulnerable group.

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