Coordinate upregulation of guanylin and uroguanylin expression by hypertonicity in HT29-18-N2 cells.

Guanylin and uroguanylin are particulate guanylate cyclase-activating peptides that are secreted from the epithelia of the intestine, kidney, pancreas, and salivary gland. These peptides elicit chloride and bicarbonate secretion via the cystic fibrosis transmembrane conductance regulator. To test the hypothesis that hypertonicity mediates an increase in guanylin and uroguanylin mRNA, we subjected HT29-18-N2 to osmotic stress.

Improving Pap test turnaround time using external benchmark data and engineering process improvement tools.

Turnaround time for Papanicolaou (Pap) tests became an important service quality issue at our institution. We studied Pap test turnaround time using engineering process improvement tools and benchmarked turnaround time against data published as a College of American Pathologists Q-Probes study. An IDEF3 process map revealed the complexity of the Pap test process and the opportunities for process improvement.

Fibroblast growth factor 8 isoform B overexpression in prostate epithelium: a new mouse model for prostatic intraepithelial neoplasia.

Fibroblast growth factor 8 isoform b (FGF8b), a mitogenic and transforming polypeptide, was demonstrated to be naturally up-regulated in prostatic premalignant and malignant lesions in men. We generated four independent lines of transgenic mice with targeted overexpression of FGF8b in the prostatic epithelium using an improved rat probasin promoter, ARR(2)PB. Transgene expression in the prostate tissue was readily demonstrated by reverse transcription-PCR and localized to the prostatic epithelium by in situ hybridization.

Cytologic diagnosis of adenocarcinoma in biliary and pancreatic duct brushings.

Biliary and pancreatic duct brush specimens are relatively uncommon specimens seen by pathologists. Not only can the findings of malignancy be subtle, the implications of a malignant diagnosis can be significant. This review focuses on cholangiocarcinoma and pancreatic ductal adenocarcinoma sampled by endoscopic brush cytology, with an emphasis on diagnostic criteria for adenocarcinoma.

Prostatic intraepithelial neoplasia in mice with conditional disruption of the retinoid X receptor alpha allele in the prostate epithelium.

Retinoids, which are important regulators of cell growth, differentiation, and apoptosis, have been used in treatment or chemoprevention of multiple cancers including prostate cancer. To elucidate the mechanism of action of retinoids in the context of the prostate, we used the Cre-loxP system to disrupt the retinoid X receptor alpha (RXRalpha) gene specifically in the prostatic epithelium of the mouse. Evidence for tissue-specific gene inactivation was obtained at DNA, RNA, and protein levels.

Proguanylin secretion and the role of negative-feedback inhibition in a villous epithelial cell line.

The mechanisms of proguanylin synthesis and secretion in the intestine are incompletely understood. We designed an in vitro model to study proguanylin secretion in a model of intestinal villous epithelial cells. The C2/bbe1 cell line, a differentiated subclone of Caco-2 cells, was used to examine the direction of proguanylin secretion and the potential for feedback regulation via activators of the guanylyl cyclase C signal transduction pathway.

Bisindolylmaleimide IX facilitates tumor necrosis factor receptor family-mediated cell death and acts as an inhibitor of transcription.

Bisindolylmaleimides (Bis) were originally described as protein kinase C inhibitors. Several studies have shown that Bis potentiate tumor necrosis factor (TNF) receptor family-mediated apoptosis in lymphoid and dendritic cells, but the inhibition of protein kinase C cannot account for these effects (Zhou, T., Song, L.

Host-induced epidemic spread of the cholera bacterium.

The factors that enhance the transmission of pathogens during epidemic spread are ill defined. Water-borne spread of the diarrhoeal disease cholera occurs rapidly in nature, whereas infection of human volunteers with bacteria grown in vitro is difficult in the absence of stomach acid buffering. It is unclear, however, whether stomach acidity is a principal factor contributing to epidemic spread.

The cytologic diagnosis of low-grade transitional cell carcinoma.

Current theory suggests that transitional cell carcinoma (TCC) occurs as either of 2 disease processes, each of which has a distinct cytologic appearance and clinical course: low-grade and high-grade TCC. Urinary cytology has become a mainstay technique for monitoring disease recurrence in patients with TCC. Most cases of high-grade TCC can be diagnosed accurately in urinary cytology specimens.

Caspase-8 activation is necessary but not sufficient for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in the prostatic carcinoma cell line LNCaP.

Background: The differential sensitivity of tumor cells to TRAIL-induced apoptosis may be mediated by different intracellular inhibitors of apoptosis, and only a few reports have described the pathway(s) that are activated in response to TRAIL in prostate cells.

Methods: LNCaP was transfected with a dominant-negative form of FADD (FADD-DN) and cells were selected in the presence of hygromycin. Cell viability was estimated by calcein assay.

Contribution of death receptor and mitochondrial pathways to Fas-mediated apoptosis in the prostatic carcinoma cell line PC3.

Background: Two main pathways of apoptosis in mammalian cells have been described: the death receptor pathway and the mitochondrial pathway. Two different cell types have been identified for Fas-mediated apoptosis, each using almost exclusively one of two different signaling pathways. Human prostatic carcinoma cell line, PC3 is sensitive to Fas-mediated apoptosis, but relation of receptor and mitochondrial pathways is not clear.

Novel genes and functional relationships in the adult mouse gastrointestinal tract identified by microarray analysis.

Background & Aims: A genome-level understanding of the molecular basis of segmental gene expression along the anterior-posterior (A-P) axis of the mammalian gastrointestinal (GI) tract is lacking. We hypothesized that functional patterning along the A-P axis of the GI tract could be defined at the molecular level by analyzing expression profiles of large numbers of genes.

Methods: Incyte GEM1 microarrays containing 8638 complementary DNAs (cDNAs) were used to define expression profiles in adult mouse stomach, duodenum, jejunum, ileum, cecum, proximal colon, and distal colon.

Long-term clinical outcome of rescue balloon angioplasty compared with rescue stenting after failed thrombolysis.

Failed thrombolysis following acute myocardial infarction is associated with a poor prognosis. Balloon angioplasty with or without stenting is an established procedure in acute myocardial infarction and for failed thrombolysis (rescue percutaneous transluminal coronary angioplasty [PTCA]). Intracoronary stenting improves initial success rates, decreases incidence of abrupt closure, and reduces the rate of restenosis after angioplasty.

Detecting recurrent bladder cancer: new methods and biomarkers.

In this review, a series of biomarkers and molecular assays are compared with conventional urothelial cytology in their ability to detect recurrent bladder cancer. The tests considered in detail include the BTA test, NMP 22 test, DNA ploidy measurements, telomerase determinations and microsatellite instability assays. Although all of these measurements show some degree of improvement for cancer detection, the microsatellite instability assay shows the highest sensitivity and specificity.

Randomized, controlled human challenge study of the safety, immunogenicity, and protective efficacy of a single dose of Peru-15, a live attenuated oral cholera vaccine.

Peru-15 is a live attenuated oral vaccine derived from a Vibrio cholerae O1 El Tor Inaba strain by a series of deletions and modifications, including deletion of the entire CT genetic element. Peru-15 is also a stable, motility-defective strain and is unable to recombine with homologous DNA. We wished to determine whether a single oral dose of Peru-15 was safe and immunogenic and whether it would provide significant protection against moderate and severe diarrhea in a randomized, double-blind, placebo-controlled human volunteer cholera challenge model.

Prostatic tumor cell plasticity involves cooperative interactions of distinct phenotypic subpopulations: role in vasculogenic mimicry.

Background: Tumor cell plasticity represents a significant clinical challenge in that the fate and function of tumor cells can be elusive until a tumor mass is evident. A remarkable example of plasticity is tumor cell vasculogenic mimicry, recently described in aggressive uveal and cutaneous melanoma, in addition to ovarian carcinoma, whereby tumor cells express endothelial-associated genes and form de novo vasculogenic-like networks in three-dimensional (3-D) culture. In the current investigation, we examined whether there is evidence for vasculogenic mimicry in heterogeneous prostatic neoplasms.

Expression of prostate specific antigen (PSA) is negatively regulated by p53.

Although prostate-specific antigen (PSA) is considered a uniquely important tumor marker and is broadly used for early detection of prostate cancer, the molecular mechanisms underlying its elevated expression in tumors have been unknown. By using cDNA microarray gene expression profiling, we found a fourfold increase in the PSA mRNA level in prostatic carcinoma cell line LNCaP, in which the p53 pathway was suppressed by a dominant negative p53 mutant. Consistently, p53 suppression caused a 4-8-fold increase in secretion of PSA protein in culture medium, suggesting that PSA gene expression is under negative control of p53.

Implementing an evidence-based acute gastroenteritis guideline at a children's hospital.

Background: Guidelines for preventing and treating acute gastroenteritis (AGE) have generally not been incorporated into medical practice. An evidence-based clinical practice guideline was adapted from national guidelines to meet the practice styles characterizing care in southwestern Ohio and implemented at the Children's Hospital Medical Center (Cincinnati). Its efficacy was assessed in terms of emergency department (ED) encounters and admissions, mean and total hospital costs, and mean length of hospitalization.

Nondestructive near-infrared spectroscopic measurement of multiple analytes in undiluted samples of serum-based cell culture media.

An adaptive calibration procedure is used to build selective multivariate calibration models for the measurement of glucose, lactate, glutamine, and ammonia in undiluted serum-based cell culture media. This adaptive procedure removes metabolism-induced covariance between these analytes in a series of calibration samples collected during the cultivation of PC-3 human prostate cancer cells. Partial least-squares calibration models are generated from single-beam near-infrared (NIR) spectra collected over the 4800- to 4200-cm(-1) combination spectral range.

A human volunteer challenge model using frozen bacteria of the new epidemic serotype, V. cholerae O139 in Thai volunteers.

A total of 35 volunteers were recruited for an IRB-approved inpatient dose-escalation challenge. The goal was to identify a dose that produced an observed cholera attack rate > or =80% and an illness of sufficient severity during the defined study period such that the model would be useful for determining vaccine protection. Volunteers were challenged in groups of 5 with V.

Percutaneous transluminal coronary angioplasty (PTCA) combined with stenting improves clinical outcomes compared with PTCA alone in acute myocardial infarction.

Balloon angioplasty in acute myocardial infarction is an established procedure. The procedure is limited by the potential for early abrupt reocclusion (18-20%) and other complications. Coronary stenting improves the initial success rate, decreases the incidence of abrupt closure, and is associated with a reduced rate of restenosis.

Long-term clinical outcome of stenting in primary and rescue angioplasty in acute myocardial infarction.

Long-term clinical outcome after use of stents in primary and rescue coronary angioplasty for treatment of acute myocardial infarction has not been described in detail. This study was conducted to evaluate long-term (more than one year) outcome in patients treated for acute myocardial infarction with stents. Between January 1, 1997 and September 1997, 101 consecutive patients had coronary artery stents implanted either for primary treatment of myocardial infarction or after failed thrombolytic therapy.

Increases in guanylin and uroguanylin in a mouse model of osmotic diarrhea are guanylate cyclase C-independent.

Background & Aims: Guanylin and uroguanylin are peptide hormones that are homologous to the diarrhea-causing Escherichia coli enterotoxins. These secretagogues are released from the intestinal epithelia into the intestinal lumen and systemic circulation and bind to the receptor guanylate cyclase C (GC-C). We hypothesized that a hypertonic diet would result in osmotic diarrhea and cause a compensatory down-regulation of guanylin/uroguanylin.