The intestinal epithelium is continuously and rapidly renewed by a process involving cell generation, migration, and differentiation, from the stem cell population located at the bottom of the crypt to the extrusion of the terminally differentiated cells at the tip of the villus. Because of the lack of normal human intestinal cell models, most of our knowledge about the regulation of human intestinal cell functions has been derived from studies conducted on cell cultures generated from experimental animals and human colon cancers. However, important advances have been achieved over recent years in the generation of normal human intestinal cell models. These models include (a) intestinal cell lines with typical crypt cell proliferative noncommitted characteristics, (b) conditionally immortalized intestinal cell lines that can be induced to differentiate, and (c) primary cultures of differentiated villuslike cells that can be maintained in culture for up to 10 days. Each of these models should help in the investigation of the specific aspects of human intestinal function and regulation. Furthermore, taken together, these models provide an integrated system that allows an in vitro recapitulation of the entire crypt-villus axis of the normal human small intestine.

Integrins are important mediators of cell-laminin interactions. In the small intestinal epithelium, which consists of spatially separated proliferative and differentiated cell populations located, respectively, in the crypt and on the villus, laminins and laminin-binding integrins are differentially expressed along the cryptvillus axis. One exception to this is the integrin ␣ 6 ␤ 4 , which is thought to be ubiquitously expressed by intestinal cells. However, in this study, a re-evaluation of the ␤ 4 subunit expression with different antibodies revealed that two forms of ␤ 4 exist in the human intestinal epithelium. Furthermore, we show that differentiated enterocytes express a full-length 205-kDa ␤ 4 A subunit, whereas undifferentiated crypt cells express a novel ␤ 4 A subunit that does not contain the COOH-terminal segment of the cytoplasmic domain (␤ 4 A ctd؊ ). This new form was not found to arise from alternative ␤ 4 mRNA splicing. Moreover, we found that these two ␤ 4 A forms can associate into ␣ 6 ␤ 4 A complexes; however, the ␤ 4 A ctd؊ integrin expressed by the undifferentiated crypt cells is not functional for adhesion to laminin-5. Hence, these studies identify a novel ␣ 6 ␤ 4 A ctd؊ integrin expressed in undifferentiated intestinal crypt cells that is functionally distinct.

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Since noise type appears to have a more limited effect on reaction thresholds, adjusting alarms based on a global dBA method appears preferable to methods based on masked detection thresholds. However, while the >0 dB SNR recommended in ISO 9533 seems adequate for unprotected listening, an additional 5-10 dB may be warranted to elicit the same reaction when the selected HPD is used.