Quantitative metrics for evaluating parallel acquisition techniques in diffusion tensor imaging at 3 Tesla.

Objectives: Single-shot echo-planar based diffusion tensor imaging is prone to geometric and intensity distortions. Parallel imaging is a means of reducing these distortions while preserving spatial resolution. A quantitative comparison at 3 T of parallel imaging for diffusion tensor images (DTI) using k-space (generalized auto-calibrating partially parallel acquisitions; GRAPPA) and image domain (sensitivity encoding; SENSE) reconstructions at different acceleration factors, R, is reported here.

Inhibitory effect of carboxylic acid group on hERG binding.

Drug-induced QT prolongation arising from drugs' blocking of hERG channel activity presents significant challenges in drug development. Many, but not all, of our benzamidine-containing factor Xa inhibitors were found to have high hERG binding propensity. However, incorporation of a carboxylic acid group into these benzamidine molecules generally leads to hERG inactive compounds regardless where the carboxyl group is tethered within the molecules.

Circles of prominence: a new theory on facial aesthetics.

Objective: To elucidate key elements of facial aesthetics through a new hypothesis called the circles of prominence.

Design: In this subjective survey, 32 persons in the medical field rated frontal-view photographs of 20 subjects in 5 categories on a 0-to-100 scale, 0 representing the most unaesthetic rating, 100, the most aesthetically pleasing. The study was conducted in an academic setting, and the subject photographs were of 9 women (aged 27-65 years) from a clinical setting and 11 women whose pictures appeared in entertainment magazines.

Histopathological changes in cases of aluminium phosphide poisoning.

Of a total of 205 poisoning deaths in our hospital in 2003, 83 cases were due to Aluminium phosphide poisoning and were further analyzed. Most vulnerable age group was 21-40 years and M:F ratio was 2:1. On naked eye examination, almost all the vital organs were found to be congested.

In vivo diffusion tensor imaging of the human calf muscle.

Purpose: To demonstrate the feasibility of in vivo calf muscle fiber tracking in human subjects.

Materials And Methods: An EPI-based diffusion tensor imaging (DTI) sequence with six-direction diffusion gradient sensitization was implemented, and DT images were acquired at 3 Tesla on five subjects using an extremity coil. The mean diffusivity, fractional anisotropy (FA), and fiber angle (with respect to the magnet z-axis) were measured in different muscles, and fibers were tracked from several regions of interest (ROIs).

EphB4 provides survival advantage to squamous cell carcinoma of the head and neck.

The receptor tyrosine kinase EphB4 and its ligand EphrinB2 play critical roles in blood vessel maturation, and are frequently overexpressed in a wide variety of cancers. We studied the aberrant expression and biological role of EphB4 in head and neck squamous cell carcinoma (HNSCC). We tested the effect of EphB4-specific siRNA and antisense oligonucleotides (AS-ODN) on cell growth, migration and invasion, and the effect of EphB4 AS-ODN on tumor growth in vivo.

Serum circulating human mRNA profiling and its utility for oral cancer detection.

Purpose: The purpose of this study is to explore the presence of informative RNA biomarkers from human serum transcriptome, and evaluate the serum transcriptome diagnostics for disease detection. Oral squamous cell carcinoma (OSCC) was selected as the proof-of-concept disease.

Patients And Methods: Blood samples were collected from patients (n = 32) with primary T1/T2 OSCC and matched healthy patients (n = 35).

Sperm protein 17 expression defines 2 subsets of primary esthesioneuroblastoma.

Esthesioneuroblastomas (ENBs) are rare malignant tumors of the nasal vault, the origin, diagnosis, and management of which are still subjects of discussion. That there is no related prognostic factor or generally recognized therapeutic regimen highlights the need for further analyses of its underlying biologic features and investigations of new marker proteins that allow more reliable clinical testing. We here show that sperm protein 17 (Sp17) is expressed in the ciliated cells of the normal olfactory epithelium and in a proportion of primary ENB lesions.

p53 apoptotic response to DNA damage dependent on bcl2 but not bax in head and neck squamous cell carcinoma lines.

Background: In many tumors, the p53 gene has been mutated or deleted. p53 null mutant mice are prone to development of a variety of neoplasms at an early age. In head and neck cancer, p53 mutations are detected in most cases.

Geometric distortion correction of high-resolution 3 T diffusion tensor brain images.

Diffusion-weighted images based on echo planar sequences suffer from distortions due to field inhomogeneities from susceptibility differences as well as from eddy currents arising from diffusion gradients. In this paper, a novel approach using nonlinear warping based on optic flow to correct distortions of baseline and diffusion weighted echo planar images (EPI) acquired at 3 T is presented. The distortion correction was estimated by warping the echo planar images to the anatomically correct T2-weighted fast spin echo images (T2-FSE).

Analysis of the brain-stem white-matter tracts with diffusion tensor imaging.

The authors have reviewed the diffusion tensor imaging (DTI) of the brain stem in 19 subjects, consisting of 15 normal volunteers and four multi-system atrophy patients. The study was performed with 1.5 T MRI scanners.

Synergistic induction of tissue factor by coagulation factor Xa and TNF: evidence for involvement of negative regulatory signaling cascades.

Enzymes of the blood coagulation pathway enhance the inflammatory response leading to endothelial dysfunction, accounting, in part, for the vascular complications occurring in sepsis and cardiovascular disease. The responses of endothelial cell activation include induction of the expression of tissue factor (TF), a membrane glycoprotein that promotes thrombosis, and of E-selectin, a cell adhesion molecule that promotes inflammation. In this report, we demonstrate synergistic interactions between the coagulation factor Xa (fXa) and the proinflammatory cytokines TNF, IL-1beta, and CD40L, leading to enhanced expression of TF and E-selectin in endothelial cells.

Therapeutic approaches in arterial thrombosis.

The current standard of care for the treatment of arterial thrombosis includes anticoagulants and three classes of antiplatelet agents--aspirin, thienopyridines and glycoprotein IIb-IIIa antagonists. Although these drugs have had a significant impact on morbidity and mortality in several patient populations, up to 15% of the high risk patients with acute coronary syndrome continue to suffer from ischemic events. This problem may occur, in part, because the platelets in many patients are non-responsive to aspirin and clopidogrel.

Synthetic inhibitors of coagulation factor Xa.

The antithrombotic efficacy of low molecular weight heparins suggest that specific inhibition of blood coagulation factor Xa (fXa) is an appropriate target for drug discovery. Clinical evidence also supports the effectiveness of warfarin, an orally bioavailable non-specific anticoagulant. The reported synthetic fXa inhibitors are directed towards the enzyme active site, and have been mostly non-inhibitory against closely related proteases, such as thrombin and activated protein C.

Salivary transcriptome diagnostics for oral cancer detection.

Purpose: Oral fluid (saliva) meets the demand for noninvasive, accessible, and highly efficient diagnostic medium. Recent discovery that a large panel of human RNA can be reliably detected in saliva gives rise to a novel clinical approach, salivary transcriptome diagnostics. The purpose of this study is to evaluate the diagnostic value of this new approach by using oral squamous cell carcinoma (OSCC) as the proof-of-principle disease.

Parametric brain MR atlases: standardization for imaging informatics.

This paper is focused on the development of normal MR brain atlases of intrinsic MR parameters. These parameters permit quantitative comparisons across imaging studies (as opposed to raw image intensity values) and are important markers of neurological diseases. The development includes fast sequences to generate three parameters (T1: spin-lattice relaxation, T2: spin-spin relaxation, and Diffusion Tensor) covering the whole brain with isotropic and high-resolution images.

In vivo diffusion tensor imaging of the human prostate.

This study demonstrates the feasibility of in vivo prostate diffusion tensor imaging (DTI) in human subjects. We implemented an EPI-based diffusion-weighted (DW) sequence with seven-direction diffusion gradient sensitization, and acquired DT images from six subjects using cardiac gating with a phased-array prostate surface coil operating in a linear mode. We calculated two indices to quantify diffusion anisotropy.

Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma.

Background: Since morbidity and mortality rates due to oral cavity and oropharyngeal squamous cell carcinoma (OSCC) have improved little in the past 30 years, early detection or prevention of this disease is likely to be most effective. Using laser-capture microdissection, we have identified the expression of 2 cellular genes that are uniquely associated with OSCC: interleukin (IL) 6 and IL-8. These cytokines may contribute to the pathogenesis of this disease, and have been linked with increased tumor growth and metastasis.

Parallel synthesis and structure-activity relationships of a series of highly potent, selective, and neutral factor Xa inhibitors.

Parallel synthesis and iterative optimization led to the discovery of a series of potent and specific factor Xa inhibitors demonstrating excellent in vitro activity with promising pharmacokinetics.

N,N-Dialkylated 4-(4-arylsulfonylpiperazine-1-carbonyl)-benzamidines and 4-((4-arylsulfonyl)-2-oxo-piperazin-1-ylmethyl)-benzamidines as potent factor Xa inhibitors.

A class of N,N-dialkylated 4-(4-arylsulfonylpiperazine-1-carbonyl)-benzamidines and 4-((4-arylsulfonyl)-2-oxo-piperazin-1-ylmethyl)-benzamidines has been discovered as potent factor Xa inhibitors with desirable in vitro and in vivo anticoagulant activity, but with low oral bioavailability. The 5-chloroindole and 6-chlorobenzo[b]thiophene groups are optimal as the factor Xa S1 binding elements. The strategy of incorporating a side chain on the piperazine nucleus to enhance binding affinity has been examined.

Relationships between stem cells and cancer stem cells.

Stem cells have been shown to exist in a variety of tissues. Recent studies have characterized stem cell gene expression patterns, phenotypes, and potential therapeutic uses. One of the most important properties of stem cells is that of self renewal.

Design, synthesis, and SAR of anthranilamide-based factor Xa inhibitors with improved functional activity.

Compound 2 containing an aminomethylbenzoyl moiety as the S4 binding motif was synthesized in order to modulate hydrophlicity of anthranilamide-based factor Xa inhibitors with substituted biphenyl P4 groups. Structure-activity relationship studies around 2 have led to a series of potent factor Xa inhibitors which are highly active in the human plasma-based thrombin generation assay with 2XTG values less than 1 microM. Compound 55 shows strong antithrombotic activity in our rabbit deep vein thrombosis model, and also exhibits good oral bioavailability and a long half life in rats.

Design, synthesis, and SAR of anthranilamide-based factor Xa inhibitors incorporating substituted biphenyl P4 motifs.

Anthranilamides 4 and 5 were designed and synthesized as selective and orally bioavailable factor Xa inhibitors. Structural modifications aimed at lowering their lipophilicity were performed at the central phenyl ring and at the S4 binding biphenyl region by incorporating water solublizing substituents. The resulting compounds (e.

Functional outcomes following palatal reconstruction with a folded radial forearm free flap.

Defects of the soft palate often occur after extirpative procedures are performed to treat oropharyngeal cancers. These defects usually result in velopharyngeal insufficiency and an alteration in speech and deglutition. Palatal prostheses have been used to circumvent this problem in the past.

1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 3: Design, synthesis and SAR of orally bioavailable benzamidine-P4 inhibitors.

Using N,N-dialkylated benzamidines as the novel P4 motifs, we have designed and synthesized a class of 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides as highly potent and selective fXa inhibitors with significantly improved hydrophilicity and in vitro anticoagulant activity. These benzamidine-P4 fXa inhibitors have displayed excellent oral bioavailability and long half-life.