Tiam1 regulates cell adhesion, migration and apoptosis in colon tumor cells

The guanine nucleotide exchange factor Tiam1 regulates numerous biologic properties including migration and invasion. We demonstrated previously that colon tumor cells biologically selected for increased migration were increased in Tiam1 expression. Cells selected for increased Tiam1 expression or that ectopically overexpress Tiam1 were increased in metastatic potential. Here, we demonstrate that Tiam1 regulates additional functions associated with metastasis, including reduced cellular adhesion and resistance to anoikis. Tiam1 effects on cellular migration are mediated through its downstream substrate, Rac. Increased Tiam1 expression also leads to anoikis-resistance, whereas decreasing Tiam1 expression by siRNA sensitizes cells to this form of apoptosis; however, Tiam1’s regulation of anoikis is Rac-independent. Staurosporine sensitivity is also Rac-independent, suggesting Tiam1’s effects on apoptosis require other effectors. As many of the observed phenotypes are characteristic of a transition of transformed epithelial cells to a mesenchymal-like phenotype, we also examined biochemical properties associated with an EMT. We demonstrate an increase in vimentin expression in cell lines that overexpress Tiam1 and have a more metastatic phenotype. Concomitant with this increase, we observe a decrease in E-cadherin expression in these cells. Lastly, we stained a panel of human colorectal specimens and adjacent normal tissue, and demonstrate that Tiam1 is overexpressed in a subset of human colorectal tumors. In summary, in colon tumor cells, Tiam1 affects multiple properties associated with acquisition of the metastatic phenotype, and may represent a marker of colon tumor progression and metastasis in a subset of tumors.     

Magnetic resonance imaging and computational fluid dynamics (CFD) simulations of rabbit nasal airflows for the development of hybrid CFD/PBPK models

The percentages of total airflows over the nasal respiratory and olfactory epithelium of female rabbits were calculated from computational fluid dynamics (CFD) simulations of steady-state inhalation. These airflow calculations, along with nasal airway geometry determinations, are critical parameters for hybrid CFD/physiologically based pharmacokinetic models that describe the nasal dosimetry of water-soluble or reactive gases and vapors in rabbits. CFD simulations were based upon three-dimensional computational meshes derived from magnetic resonance images of three adult female New Zealand White (NZW) rabbits. In the anterior portion of the nose, the maxillary turbinates of rabbits are considerably more complex than comparable regions in rats, mice, monkeys, or humans. This leads to a greater surface area to volume ratio in this region and thus the potential for increased extraction of water soluble or reactive gases and vapors in the anterior portion of the nose compared to many other species. Although there was considerable interanimal variability in the fine structures of the nasal turbinates and airflows in the anterior portions of the nose, there was remarkable consistency between rabbits in the percentage of total inspired airflows that reached the ethmoid turbinate region (~50%) that is presumably lined with olfactory epithelium. These latter results (airflows reaching the ethmoid turbinate region) were higher than previous published estimates for the male F344 rat (19%) and human (7%). These differences in regional airflows can have significant implications in interspecies extrapolations of nasal dosimetry.     

Enteroatmospheric fistula management by endoscopic gastrostomy PEG tube

Management of small‐bowel fistulas which are in an open abdomen and have no soft tissue overlay or a fistula tract involves many complications and challenges. Controlling the local leakage of enteric contents has a central role in the success of medical treatment. There are several methods to deal with fistula discharge but unfortunately, the technical solutions only partially address such problems and a definitive management of fistula discharge still remains an insoluble challenge. We describe a simple and cheap method to control fistula leakage by using a percutaneous endoscopic gastrostomy tube.     

Radiological imaging of a massive dermoid in the male pelvis

A dermold cyst, arising from the posterior aspects of the prostate and seminal vesicles, and extending into the pelvis to masquerade as a full bladder, must be exceedingly rare. Ultrasound, computed tomography and especially magnetic resonance imaging (MRI) proved to be invaluable in making the diagnosis, and MRI in particular was very useful in providing an anatomical road map for surgery.     

海风藤的原植物——腺鳞蒟与山药的比较研究

本文对模式产地的山药Piper haneei Maxim, var, hancei Maxim,和腺鳞蒟P. kancei Maxim var. squamiglanduferum Fan var. nov.进行了原植物形态特征和花序轴、花序梗、茎、叶的显微特征以及化学成分的TLC及UV比较。挥发油的GC—MS研究共鉴定出38个成分,其中28个是胡椒属植物中首次报道的成分。结果证明了在福建长期以来被认为是山药的腺鳞蒟与模式产地的山药有较大差别,尤其是腺鳞蒟叶上表面有腺鳞,是迄今为止第1个发现具有腺鳞的胡椒属植物。据此把腺鳞蒟作为新变种从山药中分出。腺鳞药是福建南部海风藤主要来源之一。     

Accuracy of methods to estimate ionized and "corrected" serum calcium concentrations in critically ill multiple trauma patients receiving specialized nutrition support

BACKGROUND: The purpose of this study was to determine the accuracy of 22 published methods to estimate serum ionized calcium (iCa) and "corrected" total serum calcium (totCa) concentrations in critically ill, multiple trauma patients. Seven of these formulas estimated iCa and 15 were directed toward predicting a "corrected" totCa. METHODS: Adult patients admitted to the trauma intensive care unit who received specialized nutrition support were consecutively recruited for study. Patients who received blood products, i.v. calcium, or therapeutic doses of heparin within 24 hours before the laboratory measurements or had a history of cancer, bone disease, parathyroid disease, hyperphosphatemia (> or = 6 mg/dL), hyperbilirubinemia (> 3.5 mg/dL), or renal failure requiring dialysis were excluded. The 22 published methods were analyzed for sensitivity, specificity, percentage false negatives, and percentage false positives for predicting hypocalcemia or hypercalcemia. RESULTS: One hundred patients were studied 4.9 +/- 3.3 days postinjury and were receiving enteral nutrition (n = 81), parenteral nutrition (n = 18), or both (n = 1) at the time of study. Twenty-one patients were hypocalcemic (iCa < or = 1.12 mmol/L) and 6 were hypercalcemic (iCa > or = 1.32 mmol/L). The mean sensitivity of the 22 methods for assessing hypocalcemia was 25% +/- 32% and the specificity was 90% +/- 18%. Although the average percentage of false positives for assessing hypocalcemia was 10% +/- 18%, the mean percentage of false negatives was inordinately high at 75% +/- 32%. The most common method for determination of "corrected" totCa concentration ["corrected" calcium = totCa + (0.8 x (4-serum albumin concentration))] had a sensitivity of only 5%. The McLean-Hastings nomogram method, the most common method for estimating serum iCa concentration, had a sensitivity of 67% but unfortunately also had a significant false-positive rate of 27%. Serum totCa correlated modestly with iCa (r2 = .334, p < .001). Those patients with a serum albumin < or = 2 g/dL (n = 43) had a significantly higher prevalence of hypocalcemia than those with a higher serum albumin concentration (37% incidence of hypocalcemia vs 10%, respectively, p < .002). CONCLUSIONS: Aberrations in calcium homeostasis are frequent (27%) in postresuscitative critically ill multiple trauma patients. Methods for predicting hypocalcemia lack sensitivity and are often associated with an unacceptable rate of false negatives. Predictive methods for estimating ionized or corrected serum concentrations should not be used. Direct measurement of serum iCa concentration is indicated for assessing calcium status for this population.