Pharmacokinetics and pharmacodynamics of propofol microemulsion and lipid emulsion after an intravenous bolus and variable rate infusion.

Background: The aim of this trial was to evaluate the induction and recovery characteristics of microemulsion propofol (Aquafol; Daewon Pharmaceutical Co., Ltd., Seoul, Korea).

Radiolabeled anti-claudin 4 and anti-prostate stem cell antigen: initial imaging in experimental models of pancreatic cancer.

Global expression profiling of pancreatic cancers has identified two cell surface molecules, claudin 4 and prostate stem cell antigen (PSCA), as being overexpressed in the vast majority of cases. Two antibodies, anti-claudin 4 and anti-PSCA, were radiolabeled with iodine 125 ((125)I) for imaging pancreatic cancer xenografts in mice using gamma scintigraphy and single-photon emission computed tomography-computed tomography (SPECT-CT). Immunofluorescence staining of intact and permeabilized Colo357 human pancreatic cancer cells showed strong extracellular staining by both anti-PSCA and anti-claudin 4.

Intracellular kinetics of non-viral gene delivery using polyethylenimine carriers.

Purpose: Polymeric nucleic acid carriers are designed to overcome one or more barriers to delivery. High molecular weight polyethylenimine (PEI) shows high transfection efficiency but exhibits high cytotoxicity (Fischer et al. Biomaterials, 24:1121-1131 (2003); Peterson et al.

Gene-specific selection against experimental fanconi anemia gene inactivation in human cancer.

The Fanconi anemia (FA) gene family comprises at least 12 genes interacting in a common pathway involved in DNA repair. To gain insight into the role of FA gene inactivation occurring in tumors among the general population, we endogenously targeted in cancer cells four FA genes that act at different stages of the FA pathway. After successful mono-allelic deletion of all genes, the sequential homozygous deletion was achieved only for FANCC and FANCG, acting upstream, but not for BRCA2 or FANCD2, acting downstream in the FA pathway.

High-throughput screening identifies novel agents eliciting hypersensitivity in Fanconi pathway-deficient cancer cells.

Inactivation of the Fanconi anemia (FA) pathway occurs in diverse human tumors among the general population and renders those tumors hypersensitive to DNA interstrand-cross-linking (ICL) agents. The identification of novel agents to which FA pathway-deficient cells were hypersensitive could provide new therapeutic opportunities and improve our molecular understanding of the FA genes. Using high-throughput screening, we assessed the growth of isogenic human cancer cells that differed only in the presence or absence of single FA genes upon treatment with 880 active drugs and 40,000 diverse compounds.

Population pharmacokinetic and pharmacodynamic models of remifentanil in healthy volunteers using artificial neural network analysis.

Aims: An ordinary sigmoid E(max) model could not predict overshoot of electroencephalographic approximate entropy (ApEn) during recovery from remifentanil effect in our previous study. The aim of this study was to evaluate the ability of an artificial neural network (ANN) to predict ApEn overshoot and to evaluate the predictive performance of the pharmacokinetic model, and pharmacodynamic models of ANN with respect to data used.

Methods: Using a reduced number of ApEn instances (n = 1581) to make NONMEM modelling feasible and complete ApEn data (n = 24 509), the presence of overshoot was assessed.

High-resolution Raman spectra with femtosecond pulses: an example of combined time- and frequency-domain spectroscopy.

Frequency-domain spectroscopy requires long pulses, whereas time-domain spectroscopy requires short pulses. This Letter demonstrates both theoretically and experimentally that simultaneous detection in frequency and time generates well-resolved spectra using intermediate-length pulses. In the case of coherent Raman spectroscopy, typical femtosecond pulses lie between the time and frequency domains.

Human AB serum and thrombin-activated platelet-rich plasma are suitable alternatives to fetal calf serum for the expansion of mesenchymal stem cells from adipose tissue.

MSCs are currently in focus regarding their clinical potential in cell therapy and tissue engineering. However, most isolation and expansion protocols for clinical-scale production of MSCs use fetal calf serum (FCS) as a supplement, which poses a potential risk for infections as well as immunological reactions. To find a suitable FCS substitute, we investigated the effects of pooled human AB serum (AB-HS) and thrombin-activated platelet-rich plasma (tPRP) on adipose tissue MSCs (AT-MSCs) with FCS as the standard control medium.

Targeting Fanconi anemia/BRCA2 pathway defects in cancer: the significance of preclinical pharmacogenomic models.

Defects in the Fanconi anemia (FA) pathway occur in subsets of diverse human cancers. The hypersensitivity of FA pathway-deficient cells to DNA interstrand cross-linking and possibly other agents renders these genes attractive targets for a genotype-based, individualized anticancer therapy. A prerequisite before clinical trials is the validation and quantification of this hypersensitivity in suitable preclinical pharmacogenomic models.

Simulations of optimized anguilliform swimming.

The hydrodynamics of anguilliform swimming motions was investigated using three-dimensional simulations of the fluid flow past a self-propelled body. The motion of the body is not specified a priori, but is instead obtained through an evolutionary algorithm used to optimize the swimming efficiency and the burst swimming speed. The results of the present simulations support the hypothesis that anguilliform swimmers modify their kinematics according to different objectives and provide a quantitative analysis of the swimming motion and the forces experienced by the body.

Nitric oxide down-regulates polo-like kinase 1 through a proximal promoter cell cycle gene homology region.

Polo-like kinase 1 (PLK1) is an evolutionarily conserved serine/threonine kinase essential for cell mitosis. As a master cell cycle regulator, p21/Waf1 plays a critical role in cell cycle progression. Nitric oxide (NO.

MKK4 status predicts survival after resection of gastric adenocarcinoma.

Hypothesis: Lack of expression of the tumor-suppressor gene MKK4 is significantly correlated with poor survival after resection of gastric adenocarcinoma.

Design: Retrospective review of medical records after construction and immunolabeling of tissue microarrays for clinical correlation.

Setting: The Johns Hopkins Hospital, Baltimore, Md.

Molecular genetics of ductal pancreatic neoplasia.

The molecular genetic profiles that characterize pancreatic ductal neoplasia have taken shape recently with the help of immunohistochemistry and the establishment of the nomenclature describing pancreatic ductal tumorigenesis. K-ras mutations frequently occur early, changes in the expression and genetic integrity of the p16 gene appear in intermediate lesions, and the inactivation of the p53, DPC4, and BRCA2 genes occur late in the neoplastic progression. Tumor-suppressor genes inactivated in pancreatic cancer such as ALK5, TGFBR2, MKK4, and STK11/LKB1 have been identified, although their roles in tumor progression are not yet well defined.

Molecular genetics and related developments in pancreatic cancer.

Cancer of the pancreas is a genetic disease. The most common genetic alterations identified to date in pancreatic cancer are activation of the K-ras oncogene (approximately 90%) and inactivation of the p16 (approximately 95%), p53 (50% to 75%), DPC4 (55%), and BRCA2 (7%) tumor suppressor genes. An understanding of the molecular genetics of carcinoma of the pancreas is important because it may help explain the aggregation of pancreatic cancer in families and may lead to the development of novel tests to detect early cancers.

Genomic copy number changes affecting the thymidylate synthase (TYMS) gene in cancer: a model for patient classification to aid fluoropyrimidine therapy.

Thymidylate synthase (TS) is an important target for 5-fluorouracil (5FU)-based therapy. The TS polymorphic 5'-untranslated region tandem repeat sequence is under investigation to guide 5FU treatment, yet current protocols omit consideration of copy number changes at the TS locus. We surveyed the TS tandem repeat sequence and found copy number changes in gastrointestinal cancers.

Beverage-agarose gel electrophoresis: an inquiry-based laboratory exercise with virtual adaptation.

A wide range of literature and experience has shown that teaching methods that promote active learning, such as inquiry-based approaches, are more effective than those that rely on passive learning. Gel electrophoresis, one of the most common laboratory techniques in molecular biology, has a wide range of applications in the life sciences. As such, we chose it as a platform to expose high school and undergraduate students to the active process of scientific inquiry in general, while specifically teaching electrophoresis.

Evaluation of histological techniques for quantifying haemodialysis arteriovenous (AV) graft hyperplasia.

Background: Assessing treatment efficacies for preventing haemodialysis arteriovenous (AV) graft stenosis requires a reproducible method for quantifying intimal hyperplasia. We identified sources of variability in three histological methods for assessing hyperplasia in a porcine AV graft model.

Methods: Carotid-jugular synthetic grafts were placed in pigs.

Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers.

Tyrosine kinases are major regulators of signal transduction cascades involved in cellular proliferation and have important roles in tumorigenesis. We have recently analyzed the tyrosine kinase gene family for alterations in human colorectal cancers and identified somatic mutations in seven members of this gene family. In this study we have used high-throughput sequencing approaches to further evaluate this subset of genes for genetic alterations in other human tumors.

Cellular pharmacokinetics and pharmacodynamics of dipyridamole in vascular smooth muscle cells.

Hemodialysis arteriovenous grafts are often plagued by stenosis at the vein-graft anastomosis, which is due to the proliferation of venous smooth muscle cells (SMCs). Perivascular delivery of dipyridamole, a potent antiproliferative agent, has been proposed for the prevention of graft stenosis. In order to develop an optimal delivery system for dipyridamole, we examined its pharmacokinetics and pharmacodynamics in human and porcine venous and arterial SMCs in vitro.

Multifocal neoplastic precursor lesions associated with lobular atrophy of the pancreas in patients having a strong family history of pancreatic cancer.

We screened 116 patients with a strong family history of pancreatic cancer using a combination of endoscopic ultrasound and computed tomography. Ten of these patients underwent surgical resection at our institution, providing an opportunity to define the morphology of pancreatic precursor lesions in patients with a strong family history of pancreatic cancer. Eight of the 10 pancreata were available and these were entirely submitted for histologic examination.

Identifying allelic loss and homozygous deletions in pancreatic cancer without matched normals using high-density single-nucleotide polymorphism arrays.

Recent advances in oligonucleotide arrays and whole-genome complexity reduction data analysis now permit the evaluation of tens of thousands of single-nucleotide polymorphisms simultaneously for a genome-wide analysis of allelic status. Using these arrays, we created high-resolution allelotype maps of 26 pancreatic cancer cell lines. The areas of heterozygosity implicitly served to reveal regions of allelic loss.