Mechanisms of a tumor marker,glutathione transferase P,expression during hepatocarcinogenesis of the rat

The molecular mechanism of any tumor marker expression may shed a light on the mechanism of the particular tumorigenesis. This idea in mind, we have been pursuing the mechanism of specific induction of the placental type glutathione transferase (GST-P) gene during hepatocarcinogenesis of the rat. Making use of advanced technologies of molecular biology including proteomic analysis, gene cloning and production of specific transgenic rats etc., we were able to identify the enhancer and the activator proteins responsible for this tumor marker expression. Negative regulatory regions and modulatory proteins were also found. The overview of this long range study and the future outlook of the problem will be discussed.     

Boronic acid-based fluorescent receptors for selective recognition of thymine glycol

Thymine glycol is the major oxidation product of thymine. The amount of thymine glycol present within cellular DNA is one marker of the extent of oxidative damage, and chemosensors for thymine glycol have therefore a number of potential applications. In continuation of our studies devoted to the detection of modified nucleosides, we report herein our results toward the fluorescence detection of thymine glycol at both the nucleoside and the oligonucleotide levels using boronic acid sensors. These receptors show significant fluorescence enhancements and high selectivities in aqueous conditions upon binding with thymine glycol.     

Stroboscopic signs associated with benign lesions of the vocal folds

Stroboscopic signs were systematically rated for a group of 80 patients with benign vocal fold lesions, most of whom had either a nodule or a polyp. Each group revealed a characteristic pattern of ranking of signs and exhibited differences of most predominant signs. The results of the ratings were submitted to a multiple discriminant analysis to determine if post hoc stroboscopic ratings could be used to correctly classify patients into one of four diagnostic groups and into one of two treatment groups. All patients except one were correctly classified into the diagnostic groups, and all were correctly classified into the treatment groups. The important signs for classifying patients into the diagnostic groups were roughness of the edge of the affected vocal fold, phase closure pattern, and phase symmetry. The important signs for classifying patients into the treatment groups were roughness of the edge of the affected vocal fold, glottal closure configuration, and vibration characteristics of the affected (or more affected) vocal fold. The results suggest that objective evaluation of stroboscopic examinations can be valuable in correctly diagnosing patients and in selecting the proper treatment regimen for the patient.     

Effects of Bases on the Stabilities of Nucleoside C4'''' Radicals

C4'-H bond dissociation enthalpies of nucleosides were predicted using theoretical methods to a precision of 1-2 Kcal/mol. It was found that the stability of the C4' nucleoside radical is slightly dependent on the base. The orders of stability are dA < dG < dT < dC for deoxynucleosides and U < G < A = C for nucleosides.     

Mechanistic Insight into the Photoinduced Damage of an Unnatural Base Pair

Chemical- and photostability of unnatural base pairs (UBPs) are important to maintain the genetic code integrity, and critical for developing healthy semisynthetic organisms. As reported, dTPT3 was less stable upon irradiation, and thus might act as a pervasive photosensitizer to induce oxidative damage within DNA, causing harm to living semi-synthetic organisms when exposed to UVA radiation. However, there was no knowledge about molecular-level understanding of this damage process. In this paper, we not only identified four photoproducts of dTPT3, including desulfur-dTPT3 (dTPT3^H), TPT3 sulphinate (TPT3^SO2), TPT3 sulphonate (TPT3^SO3) and TPT3-thioTPT3 (TPT3^STPT3), but also established a Type II photosensitized oxidation mechanism. In addition, the antioxidant (sodium ascorbate) was able to effectively inhibit the photoproducts formation of dTPT3 and dTPT3 in DNA, suggesting that a reductive environment might protect DNA bearing dTPT3 against UVA oxidation and ameliorate its adverse biological effects. The comprehensive understanding of TPT3’ photochemical stability will give researchers helpful guidance to design more photostable UBPs and construct healthier semisynthetic organisms.     

New Visualization Technique with a Three-Dimensional Video-Assisted Stereoendoscopic System: Application of the BVHIS Display Method During Endolaryngeal Surgery

A three-dimensional video-assisted stereoendoscopic system (3D video system) developed by the Shinko Optical Company, Ltd. (Tokyo, Japan), and referred to as the binocular vision by horizontal image shifting display method (BVHIS display method), has been developed to digitally process ordinary video signals obtained with a video camera connected to a direct videolaryngoscope. The three-dimensional video system provides the surgeon with stereoendoscopic video images and enhances the ability of the surgeon to perform delicate endoscopic procedures. The three-dimensional video-assisted stereoendoscopic laryngosurgical procedure and its underlying principles are described in this paper. A total of 12 patients with laryngeal lesions causing dysphonia underwent three-dimensional video-assisted stereoendoscopic laryngosurgery. Although the video image obtained with the BVHIS display method is only pseudo-three-dimensional, this method enables the surgeon to perceive both depth perception and realism. We describe a surgical procedure using this new visualizing technique and the underlying principles of the technique. Preoperative and postoperative evaluations of the patients' vocal functions are also described. This system is a useful tool for the treatment of laryngeal lesions causing dysphonia.     

MR characteristics of neoplasms and vascular malformations associated with epilepsy

We assessed the magnetic resonance (MR) imaging characteristics of two categories of epileptogenic substrates, neoplasms, and vascular malformations, to determine MR sensitivity and typical imaging features. A blinded retrospective analysis was performed on MR scans from 41 patients who had a neoplasm or vascular malformation surgically resected as treatment for medically refractory epilepsy. Abnormalities were assessed for sensitivity of MR detection, prediction of pathologic category, location, calvarial remodelling, signal intensity, and effect on adjacent tissue. Pathologic findings consisted of 33 tumors and 8 vascular malformations. We correctly localized 100% of the 41 lesions and predicted the correct pathologic category for 95% of these lesions. Neoplastic and vascular lesions (NVLs) associated with epilepsy had certain characteristic features. The temporal lobe was the most common site for NVL, involved in 68%. NVL were located in the brain periphery in 85% and remodelled the calvarium in 32%. NVL were associated with mass effect in 61%, volume loss in 1%, and no effect on adjacent tissue in 37%. NVL associated with epilepsy can be detected with high sensitivity using MR imaging. The temporal lobe location, cortical involvement, and calvarial remodelling are findings typical of NVL. MR characteristics can successfully predict the pathologic substrate of these lesions.     

A fast tissue stiffness-dependent elastography for HIFU-induced lesions inspection

To monitor HIFU-induced lesion with elastography in quasi-real time, a fast correlation based elastographic algorithm using tissue stiffness–dependent displacement estimation (SdDE) is developed in this paper. The high time efficiency of the proposed method contributes to the reduction on both the number of the displacement points and the computational time of most of the points by utilizing local uniformity of the tissue under HIFU treatment. To obtain admirable comprehensive performance, the key algorithm parameter, a threshold to densify the displacement points, is optimized with simulation over a wedge-inclusion tissue model by compromising the axial resolution (AR) and the computational cost. With the optimum parameter, results from both simulations and phantom experiments show that the SdDE is faster in about one order of magnitude than the traditional correlation based algorithm. At the same time, other performance parameters, such as the signal-to-noise ratio (SNRe), the contrast-to-noise ratio (CNRe) and the axial resolution (AR), are superior to or comparable with that obtained from the traditional algorithm. In vitro experiments on bovine livers validate the improvement on the time efficiency under the circumstances of real tissue and real radio frequency (RF) signal. This preliminary work implies potential of the SdDE in dynamic or close real time guidance and monitoring of HIFU treatment.     

Crystal Structure of the T(6‐4)C Lesion in Complex with a (6‐4) DNA Photolyase and Repair of UV‐Induced (6‐4) and Dewar Photolesions

UV‐light irradiation induces the formation of highly mutagenic lesions in DNA, such as cis‐syn cyclobutane pyrimidine dimers (CPD photoproducts), pyrimidine(6‐4)pyrimidone photoproducts ((6‐4) photoproducts) and their Dewar valence isomers ((Dew) photoproducts). Here we describe the synthesis of defined DNA strands containing these lesions by direct irradiation. We show that all lesions are efficiently repaired except for the T(Dew)T lesion, which cannot be cleaved by the repair enzyme under our conditions. A crystal structure of a T(6‐4)C lesion containing DNA duplex in complex with the (6‐4) photolyase from Drosophila melanogaster provides insight into the molecular recognition event of a cytosine derived photolesion for the first time. In light of the previously postulated repair mechanism, which involves rearrangement of the (6‐4) lesions into strained four‐membered ring repair intermediates, it is surprising that the not rearranged T(6‐4)C lesion is observed in the active site. The structure, therefore, provides additional support for the newly postulated repair mechanism that avoids this rearrangement step and argues for a direct electron injection into the lesion as the first step of the repair reaction performed by (6‐4) DNA photolyases.