Late phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical cancer. ETP 21 Study Group--Cervical Cancer Group

We conducted a multi-site late phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical cancer in cooperation with 32 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Treatment cycles were to be repeated at 4- to 5-week intervals. Eighty patients were enrolled and 70 patients were evaluated. The overall response rate (95% CI), including one complete response patient and 18 partial response patients, was 27.1% (19/70). The most commonly observed toxicity was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were gastrointestinal toxicities such as anorexia, nausea, stomatitis and vomiting, as well as fatigue and alopecia. These adverse effects were well tolerated and controlled with medications. From these results we concluded oral etoposide administered for 21 consecutive days was an effective drug against cervical cancer.     

Left ventricular regional systolic motion in patients with right ventricular pressure overload

The highly reactive and cytotoxic hydroxyl radical (OH) was found by electrochemical detection to be produced in reactions involving hydrogen peroxide (H2O2) and the nitric oxide (NO) donor diethylamine- NO complex. Using aromatic hydroxylation of salicylate as a specific indicator of OH, three salicylate hydroxylation products were identified; catechol, 2,3- and 2,5-dihydroxybenzoic acid. Four additional compounds were detected but not identified. The interactions of H2O2 and NO represent a biologically feasible reaction mechanism that can account for OH-induced damage in cellular environments where transition metal ions are unavailable for participation in the superoxide-mediated Fenton reaction. The ability of the NO/H2O2 complex to generate OH independently of iron or other transition metals provides a new focus for studies concerned with the origin of tissue-specific damage caused by oxygen-derived species.     

Efficient directional cloning of recombinant adenovirus vectors using DNA-protein complex

We describe an efficient cloning system utilizing adenoviral DNA-protein complexes which allows the directional cloning of genes into adenoviral expression vectors in a single step. DNA-protein complexes derived from a recombinant adenovirus (AVC2.null) were isolated by sequential use of CsCl step gradients followed by isopycnic centrifugation in a mixture of CsCl and guanidine HCl. AVC2.null is an adenoviral expression vector containing unique restriction sites between the human CMV-IE promoter and the SV40 intron/polyadenylation site. Transgenes were prepared for cloning into this vector by introduction of compatible restriction sites by PCR. A vector expressing rat granulocyte-macrophage colony-stimulating factor (GM-CSF) was constructed using DNA-protein complex as well as by traditional recombination techniques. The efficacy of our adenoviral cloning system utilizing DNA-protein complex was two logs higher than that seen using homologous recombination. All viruses generated by directional ligation of the insert into the vector DNA-protein complexes contained the desired transgene in the correct orientation. This technique greatly simplifies and accelerates the generation of recombinant adenoviral vectors.     

Fiberscope-assisted evaluation of prereconstructed and postreconstructed external auditory canal

The malignant tumors of the external auditory canal often invade the middle ear area through the narrow canal, so it is difficult to determine the surgical excisional margin. A patient undergoing external auditory canal reconstruction following excision of a squamous cell carcinoma using a chondrocutaneous flap and fiberscope-assisted preoperative and postoperative diagnoses are described. We obtained good patency of the canal postoperatively. This technique is quite simple and easy to use. We believe fiberscope-assisted surgery is useful for extracting lesions in small areas. In the future, its application will extend to the area of plastic surgery.     

Wheel/rail contact dynamics in turnout negotiations with combined nodal and non-conformal contact approach

In railroad turnouts, geometries of tongue and crossing rails are very complex and their shapes are changing along the track. Therefore, wheels are subjected to not only tread and flange contacts, but also the back-of-flange and top-of-flange contacts in the case of spring switches of tram vehicles. For this reason, one needs to deal with significant jumps in contact points for solving wheel/rail contact problems in turnout, and an accurate prediction of jumps in contact points is one of the most important issues that need to be carefully handled in the dynamic simulation of vehicle/turnout interactions. In this investigation, a numerical procedure that can be used for solving such a complex wheel/rail contact problem in turnout is proposed. In particular, a combined nodal and non-conformal contact approach is developed such that significant jumps in contact points are detected using the nodal search, while the exact location of contact point is then determined with continuous surface parameterizations using non-conformal contact equations. With this combined nodal and non-conformal contact approach for the contact geometry analysis of vehicle/turnout interactions, multiple look-up contact tables can be generated in an efficient way without losing accuracy. Since detailed contact search is performed off-line to obtain look-up contact tables, significant changes in contact points in turnout can be efficiently predicted on-line with tabular data to be interpolated in a standard way. Several numerical examples are presented in order to demonstrate the use of the numerical procedure developed in this investigation.     

Preparation and characterization of porous and electrically conducting carbon-clay composites

Porous and electrically conducting carbon-clay composites were prepared by firing mixtures of carbon powder (0 to 20 wt%) and clay minerals. They showed porosity of 50 to 65% and had high mechanical strength (compressive strength = 130 to 400 kg cm^–2) as well as high resistance against thermal oxidation in air. Their electrical conductivity, , increased with increasing carbon content levelling off at about 20 wt% of carbon content to give a value of about 2 S cm^–1. Formation of carbon chains is considered to be responsible for the electrical conduction in the composite, and a model to correlate the electrical conductivity with the carbon content has been proposed by modifying a model previously proposed by Scarisbrick.     

Crystallization of potassium titanate from the amorphous phase

By using amorphous potassium titanates as the starting materials, a sintered body of K₂Ti₄O₉ or K₂Ti₆O₁₃ with porous and fibrous textures was prepared. K₂Ti₂O₅ and a new phase, K₆Ti₄O₁₁ were synthesized by the thermal reaction of KNO₃ with TiO₂ at 1000° C for 10 to 20 h. On leaching in water to expel excess of potassium ions, both phases became amorphous. After mixing and moulding these amorphous materials in the desired proportion, a sintered body containing fibrous crystals of K₂Ti₄O₉ was readily fabricated by heating at 1000° C for 12 h. When 5 wt % B₂O₃ was added to the amorphous phases, single phase K₂Ti₆O₁₃, with a fibrous texture grew well on heating at 1000° C for 12 h. Addition of PVA polymer to the amorphous phases was responsible for controlling the porosity of the sintered body, e.g. about 52% theoretical density at 20 wt% PVA polymer. The optimum conditions for preparing the amorphous phases were systematically examined and the effect of the chemical reaction environments, such as different crucible materials on the calcination of KNO₃ and TiO₂ were also discussed.     

铝合金局部加压凝固及流动数值模拟的研究

局部加压方法是压铸中用于消除铸件厚壁处缩孔缺陷的一种新工艺.本研究通过实验模型测量了不同加压条件下铸件的冷却曲线,分析了局部加压引起的凝固变化.考虑局部加压引起的补缩流动,通过适时修改网格文件、初始和边界条件的方法,模拟了局部加压过程中铝合金的凝固及流动变化,并与实验结果进行了对比,二者基本吻合.     

Alzheimer’s Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment

Alzheimer’s disease (AD) is an age-related and progressive neurodegenerative disorder. It is widely accepted that AD is mainly caused by the accumulation of extracellular amyloid β (Aβ) and intracellular neurofibrillary tau tangles. Aβ begins to accumulate years before the onset of cognitive impairment, suggesting that the benefit of currently available interventions would be greater if they were initiated in the early phases of AD. To understand the mechanisms of AD pathogenesis, various transgenic mouse models with an accelerated accumulation of Aβ and tau tangles have been developed. However, none of these models exhibit all pathologies present in human AD. To overcome these undesirable phenotypes, APP knock-in mice, which were presented with touchscreen-based tasks, were developed to better evaluate the efficacy of candidate therapeutics in mouse models of early-stage AD. This review assesses several AD mouse models from the aspect of biomarkers and cognitive impairment and discusses their potential as tools to provide novel AD therapeutic approaches.     

Net shape formation of sub-micron alumina with reduced flaws by high-speed centrifugal compaction process

A new compacting method for powder materials is presented. High-Speed Centrifugal Compaction Process (HCP) utilizes centrifugal force of about 10,000 g for the compaction. HCP is suitable for net shape compaction of fine sub-micron and nano-powders. HCP possesses a unique compacting mechanism that is different from other colloidal processes including Pressure Casting (PC), and has a number of useful characteristics. HCP has a higher compacting speed than PC, wide applicability for net shape formation, as well as a defect removing function. Because of homogeneous and flawless green microstructure, HCP alumina shows superior sinterability and higher strength and hardness than most of other aluminas. This article is based on a presentation made in the symposium “The 3rd KIM-JIM Joint Symposium on Advanced Powder Materials“, held at Korea University, Seoul, Korea, October 26–27, 2001 under auspices of The Korean Institute of Metals and Materials and The Japan Institute of Metals.