SummaryCo-ordinate expression of genes associated with pathogenicity in Vibrio cholerae requires two transcription activators, ToxR and ToxT. Work carried out to date suggests that ToxR activates transcription of the toxT gene and that ToxT directly activates transcription of several genes whose products play a role in colonization or CT production by V. cholerae. Previous work also suggests that ToxR can directly activate transcription of the CT operon (ctxAB) independently of ToxT, thereby implying a degree of complexity in control of the ctxAB operon not found with other genes of the ToxR regulon. We tested the regulatory cascade model of virulence gene expression by constructing strains of classical and El Tor V. cholerae deleted for the coding sequence for the putative DNA-binding domain of toxT. Phenotypic analysis of these strains suggests that V. cholerae has ToxTdependent and ToxT-independent branches of its virulence regulon. The results also raise questions about the precise role for ToxR in activation of ctxAB transcription.

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The protozoan parasite Cryptosporidium parvum invades intestinal epithelial cells and can cause life-threatening diarrhea in immunocompromised individuals. Despite the clinical importance of this organism, much remains to be learned about the pathogenesis ofC. parvum-induced diarrhea. To explore the role of the intestinal inflammatory response in C. parvumdisease, using C. parvum oocysts we infected human intestinal xenografts in severe combined immunodeficient (SCID) mice. Seven days after infection, we found levels of human tumor necrosis factor alpha and interleukin-8 in C. parvum-infected human intestinal xenografts that were significantly higher than those seen in uninfected control xenografts. These results demonstrate that human intestinal cells produce proinflammatory cytokines in response to C. parvum infection and establish SCID-HU-INT mice as a model system to study the interactions ofC. parvum with the human intestine.

Background. The purpose of this study was to demonstrate that pretherapeutic CT of patients with primary laryngeal cancer results in stage migration, therefore affecting laryngeal cancer outcome data.Methods. We retrospectively reviewed the medical records of 90 patients with primary laryngeal cancer diagnosed between January 1, 1995, and December 31, 1997, at a university hospital.Results. The disease in 15 (17%) of 90 patients was reclassified into a new TNM stage after pretherapeutic CT. As a result, stage-specific survival rates improved in three of four TNM stages, even though average survival for the entire cohort did not change.Conclusions. The TNM staging system is not a temporally stable classification and prediction system, because TNM assignment varies on the basis of the type of pretherapeutic evaluation. Outcome data for patients with laryngeal cancer must account for the introduction of new technologies that affect our ability to diagnose and stage this disease. Advanced imaging studies, such as CT, MRI, and positron emission tomography (PET), of head and neck malignancies are now considered the standard of care for pretherapeutic staging and treatment consideration. Numerous authors have shown that CT improves the clinicians' ability to determine the anatomic extent of the neoplasm. 1 -8 Brehn et al 9 demonstrated that head and neck tumors in different anatomic sites may undergo a change in TNM stage after pretherapeutic CT. In their study, hypopharyngeal neoplasms were most likely to change TNM stage, whereas laryngeal neoplasms were least likely to change TNM stage. It has been demonstrated that this stage migration 10,11 will influence stage-specific outcome and make the TNM stage-specific prognostic estimates less stable over time as new imaging tools are introduced and applied. Feinstein et al 10 first demonstrated this stage migration phenomenon in a large cohort of patients with primary lung cancer. Feinstein et al were able to demonstrate that improvements in pretherapeutic imaging over time resulted in an improvement in stage-specific

Our results reaffirm the importance of several established risk factors for congenital HL, but suggest that BPD is an important predictor in high-risk populations. Whether these risk factors are causal or merely associated in congenital HL remains to be determined.