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Biomedical subjects

C Yeo

Publications and source records attributed to C Yeo.

7 recordsLinked to original sources

Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms.

Nodal ligands are essential for the patterning of chordate embryos. Genetic evidence indicates that EGF-CFC factors are required for Nodal signaling, but the molecular basis for this requirement is unknown. We have investigated the role of Cripto, an EGF-CFC factor, in Nodal signaling. We find that Cripto interacts with the type I receptor ALK4 via the conserved CFC motif in Cripto. Cripto interaction with ALK4 is necessary both for Nodal binding to the ALK4/ActR-IIB receptor complex and for Smad2 activation by Nodal. We also find that Nodal can inhibit BMP signaling by a Cripto-independent mechanism. Inhibition appears to be mediated by heterodimerization between Nodal and BMPs, indicating that antagonism between Nodal and BMPs can occur at the level of dimeric ligand production.

Activin Receptors, Type I↗

Use of polymerase chain reaction to diagnose a natural outbreak of mouse hepatitis virus infection in nude mice.

The enormous cost of eliminating mouse hepatitis virus (MHV) from a mouse colony demands that a confirmed etiologic diagnosis be made to justify the necessary remedial action. We describe an outbreak of MHV in nude mice in which histopathologic findings provided a presumptive diagnosis, but results of serologic testing of affected nude mice and immunocompetent sentinels were negative. Results of transmission electron microscopy of liver specimens from affected mice were equivocal. Confirmation of the etiopathogenesis was eventually provided by reverse transcriptase-polymerase chain reaction (RT-PCR), using primers with nested sequences directed to two separate but highly conserved regions of the MHV genome. This procedure detected MHV in the liver of an affected nude mouse and in a sentinel, although in the latter a positive result was obtained only because of the increased sensitivity of nested primers used in a second round of amplification. Virus was not detected in cell lines that had been injected into the mice, and the source of the outbreak was not found. These results indicate the applicability of RT-PCR for detecting MHV in a field situation while also illustrating that conventional, complementary techniques still have an essential role in reaching a diagnosis. It is recommended that specimens should be taken for histologic examination and serologic testing, as well as for molecular studies when MHV infection is suspected.

Animals↗

Immunohistochemical evaluation of HER-2/neu expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasms.

Although several morphological and molecular genetic studies have implicated various grades of pancreatic duct hyperplasia as precursor lesions to infiltrating pancreatic adenocarcinoma, the identity of preinvasive pancreatic neoplasms remains controversial. In the present study, the authors examined the expression of the epidermal growth factor receptor homologue, HER-2/neu (c-erbB-2), in pancreatic duct lesions adjacent to infiltrating pancreas cancers in a series of 19 cases of pancreatic duct adenocarcinoma. HER-2/neu expression was examined because it has been identified in a proportion of infiltrating pancreas cancers and because it may provide early neoplasms with a growth advantage over adjacent nonneoplastic epithelium. In normal pancreatic ducts and ductules, HER-2/neu expression was absent in all but one case. By contrast, HER-2/neu was expressed in 82% (P = .008 vs normal ) of ducts with flat mucinous hyperplasia, 86% (P = .03 vs normal) of ducts with papillary mucinous hyperplasia without atypia, 92% (P = .001 vs normal) of ducts with atypical papillary mucinous hyperplasia, and all specimens with carcinoma in situ. HER-2/neu expression was observed in 69% (P = .002 vs normal) of the moderately differentiated infiltrating carcinomas and none of the poorly differentiated infiltrating carcinomas. These data establish HER-2/neu as a potential mediator of growth factor-related signal transduction in pancreatic duct lesions, and provide additional support for the hypothesis that lesions formerly regarded as various grades of hyperplasia instead may represent intraepithelial neoplasms with the potential for subsequent invasion and metastasis.

Adenocarcinoma↗

The role of substance P in the control of gastric acid secretion.

Experiments were performed to determine whether substance P plays a physiologic role as an enterogastrone. Basal substance P levels averaged 6.4 +/- 0.2 pg/ml in dogs prepared with gastric and duodenal fistulas. Infusion of substance P at 5 ng/kg/min increased circulating hormone concentrations by more than 1 pg/ml and inhibited pentagastrin-stimulated (4 micrograms/kg/hr) gastric acid secretion by 44% (from 10.9 +/- 1.8 to 6.1 +/- 1.6 mEq/30 min); a similar dose of substance P (7 ng/kg/min) did not alter gastrin levels from the basal level of 19.8 +/- 1.2 fmol/ml. Duodenal acidification (with 0.1N HCl at 5 ml/min for 10 minutes) similarly inhibited pentagastrin-stimulated gastric fistula output (from 8.2 +/- 0.9 to an average of 5.0 +/- 0.9 mEq/30 min for the 30 minutes after irrigation) but did not alter circulating substance P levels. Thus, although physiologic concentrations of substance P inhibit gastric fistula output, this peptide does not seem to be involved in the endogenous acid-mediated duodenal control of acid secretion.

Animals↗