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学位の種別: 課程博士, 審査委員会委員 : （主査）東京大学教授 村上 誠, 東京大学教授 廣瀬 謙造, 東京大学教授 山内 敏正, 東京大学講師 山本 林, 東京大学講師 池田 一穂

Objective: Survivin has been identified as a protein expressed in cancer cells and a member of the inhibitor-of-apoptosis protein family. Recent studies suggest that the expression of survivin increases during the G2/M phase of the cell cycle, and may be used in clinical prognosis. We examined whether survivin expression in human gliomas would be a correlative of prognosis. Methods: We prepared polyclonal anti-survivin serum to establish a survivin index for stained sections, using an immunohistochemical procedure, according to the method used for scoring MIB-1 index, and then stained 29 paraffin-embedded sections from surgical specimens of 29 patients who were classified into three grades of World Health Organization with the mean age of low grade astocytoma (grade II) being 34.7; anaplastic astrocytoma (grade III), 48.8; and glioblastoma multiform (grade IV), 58.4. Results: On staining with the anti-survivin antiserum, all specimens contained positive cells, but the survivin index was heterogeneous among grades. The mean percentage of immunoreactive cells in each specimen was 70.0 (SD 18.2) in grade II, 81.3 (16.5) in grade III, and 85.0 (13.6) in grade IV. Then we compared the survivin index to the MIB-1 index and found that in low-grade gliomas (grade II and III), the difference in survival times between the high and low survivin indexes was significant (P=0.007), whereas that between the high and low MIB-1 indexes was not significant (P=0.092).Conclusion: Survivin is more sensitive marker than MIB-1 for the evaluation of low-grade gliomas in that it helps to predict patient survival. Much larger glioma patient series are needed to validate the findings of our limited study.

Pb(Zr, Ti)O3 thin films were grown on 8-inch Ir(111)/SiO2/Si substrate by a MOCVD system aiming at application utilizing high-density ferroelectric memory (FRAM). Two types of solvents, THF and cyclohexane were used for liquid source delivery. It was found that the ferroelectric properties of the MOCVD-PZT films using cyclohexane solvent were better than them using THF solvent. By choosing cyclohexane as solvent, the MOCVD-PZT thin films showed strong ⟨111⟩ preferred orientation and the Pt/PZT/Ir capacitors exhibited promising ferroelectric performances, for instance, large switching charge (Qsw) of 56.4 uC/cm2.

Pb(Zr, Ti)O 3 (PZT) thin films were prepared on 8" φ ¯ substrate by ULVAC-MOCVD system. Thickness and compositional uniformity of PZT films were remarkably depending on the deposition conditions. Film thickness uniformity of - 3% on 8" φ ¯ subatrate was achieved by optimizing the hardware construction (O 2 -Precursor mixing and gas flow control) and deposition parameters. Compositional uniformity was also improved by controlling temperature distribution on the substrate and choosing precursors which have the close decomposition temperature. For ferroelectric properties of MOCVD-PZT films on 8" φ ¯ substrate, 2Pr above 40 w C/cm 2 were obtained throughout their measurement points.

We have evaluated the relationship between carotid atherosclerotic change and periventricular hyper intensity (PVH). PVH was studied in 66 cases with cerebral thrombosis, comparing them with another group of age-matched controls, which consisted of 29 cases with hypertension, diabetes, and hypercholesteremia. MRI (fluid attenuated inversion recovery) and B-mode carotid ultrasonography of each lesion were analyzed. Thrombosis lesions, compatible with neurological manifestation were divided into two types, cerebral cortical type (including centrum semiovale type) and small infarction in the deep subcortical type. PVH was classified into 4 grades, none, rims/caps, patchy and diffuse. Smooth PVH was, adjoining the anterior/posterior angles and the margins of the lateral ventricles, were defined as caps and rims. Irregular PVH areas, confluent with each other, were defined as patchy, while diffuse PVH areas extending below the cortex beyond the level of the corpus callosum were defined as diffuse. Carotid atherosclerosis was evaluated using B-mode carotid ultrasonography. The severity of carotid atherosclerosis was assessed by using two indicators; incidence of carotid atherosclerosis and maximum percentage diameter of the stenosis areas. Patchy and diffuse type PVH was frequent in the thrombosis group. On B-mode carotid ultrasonography, diffuse PVH was prominent in patients with stenotic change and high maximum percentage of stenosis, but none/rims/caps PVH was accompanied by variable B-mode carotid ultrasonographical findings. Six patients had ulcerated plaques and they suffered more frequently with diffuse PVH. Diffuse PVH was more frequent in cases with severe carotid stenosis than in other PVH types. These findings suggested that large vessel atherosclerosis could result in diffuse PVH.

Thin Pb(Zr, Ti)O3 films were grown on a 8-inch Ir(111)/SiO2/Si substrate by a liquid-source MOCVD system. These films showed dependency of ferroelectric properties on several deposition parameters. PZT single phase was obtained at a substrate temperature of 620°C. The film showed (111) preferred orientation and the Pt/Pb1.16(Zr0.45, Ti0.55)Ox(115nm)/Ir capacitors had excellent ferroelectric properties. The switching charge (Qsw) value (at 2V), saturation voltage (V90) and leakage current density (at 1.5V) were 47.4uC/cm2, 1.7V and 7.5E-8A/cm2 respectively. The capacitor made by using an IrOx top electrode had excellent fatigue-free property.