骨・軟部悪性腫瘍の化学療法における[201]T1シンチグラフィによる感受性予測ならびに治療効果判定に関する研究

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1134号, 学位授与年月日：平成6年3月25日,学位授与年：199

Photometric Properties of Kiso Ultraviolet-Excess Galaxies in the Lynx-Ursa Major Region

We have performed a systematic study of several regions in the sky where the number of galaxies exhibiting star formation (SF) activity is greater than average. We used Kiso ultraviolet-excess galaxies (KUGs) as our SF-enhanced sample. By statistically comparing the KUG and non-KUG distributions, we discovered four KUG-rich regions with a size of $\sim 10^\circ \times 10^\circ$. One of these regions corresponds spatially to a filament of length $\sim 60 h^{-1}$ Mpc in the Lynx-Ursa Major region ($\alpha \sim 9^{\rm h} - 10^{\rm h}, \delta \sim 42^\circ - 48^\circ$). We call this ``the Lynx-Ursa Major (LUM) filament''. We obtained $V(RI)_{\rm C}$ surface photometry of 11 of the KUGs in the LUM filament and used these to investigate the integrated colors, distribution of SF regions, morphologies, and local environments. We found that these KUGs consist of distorted spiral galaxies and compact galaxies with blue colors. Their star formation occurs in the entire disk, and is not confined to just the central regions. The colors of the SF regions imply that active star formation in the spiral galaxies occurred $10^{7 - 8}$ yr ago, while that of the compact objects occurred $10^{6-7}$ yr ago. Though the photometric characteristics of these KUGs are similar to those of interacting galaxies or mergers, most of these KUGs do not show direct evidence of merger processes.Comment: 39 pages LaTeX, using aasms4.sty, 20 figures, ApJS accepted. The Title of the previous one was truncated by the author's mistake, and is corrected. Main body of the paper is unchange

Intestinal epithelial cell-derived IL-15 determines local maintenance and maturation of intraepithelial lymphocytes in the intestine

Interleukin-15 (IL-15) is a cytokine critical for maintenance of intestinal intraepithelial lymphocytes (IELs), especially CD8αα+ IELs (CD8αα IELs). In the intestine, IL-15 is produced by intestinal epithelial cells (IECs), blood vascular endothelial cells (BECs) and hematopoietic cells. However, the precise role of intestinal IL-15 on IELs is still unknown. To address the question, we generated two kinds of IL-15 conditional knockout (IL-15cKO) mice: villin-Cre (Vil-Cre) and Tie2-Cre IL-15cKO mice. IEC-derived IL-15 was specifically deleted in Vil-Cre IL-15cKO mice, whereas IL-15 produced by BECs and hematopoietic cells is deleted in Tie2-Cre IL-15cKO mice. The cell number and frequency of CD8αα IELs and NK IELs were significantly reduced in Vil-Cre IL-15cKO mice. By contrast, CD8αα IELs were unchanged in Tie2-Cre IL-15cKO mice, indicating that IL-15 produced by BECs and hematopoietic cells is dispensable for CD8αα IELs. Expression of an anti-apoptotic factor, Bcl-2, was decreased, whereas Fas expression was increased in CD8αα IELs of Vil-Cre IL-15cKO mice. Forced expression of Bcl-2 by a Bcl-2 transgene partially restored CD8αα IELs in Vil-Cre IL-15cKO mice, suggesting that some IL-15 signal other than Bcl-2 is required for maintenance of CD8αα IELs. Furthermore, granzyme B production was reduced, whereas PD-1 expression was increased in CD8αα IELs of Vil-Cre IL-15cKO mice. These results collectively suggested that IEC-derived IL-15 is essential for homeostasis of IELs by promoting their survival and functional maturation

Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer

Transfer RNA (tRNA) activity is tightly regulated to provide a physiological protein translation, and tRNA chemical modifications control its function in a complex with ribosomes and messenger RNA5 (mRNA5). In this regard, the correct hypermodification of position G37 of phenylalanine-tRNA, adjacent to the anticodon, is critical to prevent ribosome frameshifting events. Here we report that the tRNA-yW Synthesizing Protein 2 (TYW2) undergoes promoter hypermethylation-associated transcriptional silencing in human cancer, particularly in colorectal tumors. The epigenetic loss of TYW2 induces guanosine hypomodification in phenylalanine-tRNA, an increase in -1 ribosome frameshift events, and down-regulation of transcripts by mRNA decay, such as of the key cancer gene ROBO1. Importantly, TYW2 epigenetic inactivation is linked to poor overall survival in patients with early-stage colorectal cancer, a finding that could be related to the observed acquisition of enhanced migration properties and epithelial-to-mesenchymal features in the colon cancer cells that harbor TYW2 DNA methylation-associated loss. These findings provide an illustrative example of how epigenetic changes can modify the epitranscriptome and further support a role for tRNA modifications in cancer biology

Amlodipine versus angiotensin II receptor blocker; control of blood pressure evaluation trial in diabetics (ADVANCED-J)

BACKGROUND: The coexistence of type 2 diabetes mellitus and hypertension increases the risk of cardiovascular diseases. The U.K. Prospective Diabetes Study has shown that blood pressure control as well as blood glucose control is efficient for prevention of complications in hypertensive patients with diabetes mellitus. However, some reports have shown that it is difficult to control the blood pressure and the concomitant use of a plurality of drugs is needed in hypertensive patients with diabetes mellitus. In recent years renin-angiotensin system depressants are increasingly used for the blood pressure control in diabetic patients. Particularly in Japan, angiotensin II (A II) antagonists are increasingly used. However, there is no definite evidence of the point of which is efficient for the control, the increase in dose of A II antagonist or the concomitant use of another drug, in hypertensive patients whose blood pressure levels are inadequately controlled with A II antagonist. METHODS/DESIGN: Hypertensive patients of age 20 years or over with type 2 diabetes mellitus who have been treated by the single use of AII antagonist at usual doses for at least 8 weeks or patients who have been treated by the concomitant use of AII antagonist and an antihypertensive drug other than calcium channel blockers and ACE inhibitors at usual doses for at least 8 weeks are included. DISCUSSION: We designed a multi-center, prospective, randomized, open label, blinded-endpoint trial, ADVANCED-J, to compare the increases in dose of A II antagonist and the concomitant use of a Ca-channel blocker (amlodipine) and A II antagonist in hypertensive patients with diabetes mellitus, whose blood pressure levels were inadequately controlled with A II antagonist. This study is different from the usual previous studies in that home blood pressures are assessed as indicators of evaluation of blood pressure. The ADVANCED-J study may have much influence on selection of antihypertensive drugs for treatment in hypertensive patients with diabetes mellitus. It is expected to give an important hint for considering the validity of selection of antihypertensive drugs from the aspects not only of the antihypertensive effect but medical cost-effectiveness

Regional 2-[ 18 F]fluoro-2-deoxy- d -glucose uptake varies in normal lung

2-[ 18 F]fluoro-2-deoxy- d -glucose positron emission tomography (FDG-PET) is a promising imaging procedure for detecting primary and metastatic cancer in the lungs. We have, however, failed to detect some small tumors in the lower lobes of the lungs. This study aimed to determine whether increase 18 F background activity in the dependent lower lungs is present, which could make lesion detection more difficult. We measured the standardized uptake values (SUVs) for FDG of normal lung remote from the nodular lesion in 16 patients with newly diagnosed untreated lung lesions stronlgy suspected to represent non-small cell lung cancers. In addition, 15 patients with known or suspected primary breast cancers without pulmonary lesions were included as control subjects. After PET transmission images of the thorax were obtained, approximately 370 MBq of FDG was injected intravenously and imaging was immediately begun. Patients were supine throughout the study. SUVs were determined with images obtained 50–70 min after FDG injection. Regions of interest (ROls) of 6×6 pixels were positioned over normal lung in anterior, mid, and posterior portions of upper, middle, and lower lung fields. Thus, as many as 18 ROls were positioned in each patient. The SUVs of the posterior portion were significantly higher than those of the anterior and mid portions in the population of 31 cases ( P <0.001). Also, the mean SUV of the lower lung field was significantly higher than the SUVs of the upper and middle lung fields in this population ( P <0.01). This pattern was seen among the two groups of 16 patients suspected of having lung cancer and 15 control subjects. Background 18 F activity was highest in posterior and lower lung in these patients. The maximum value of mean SUV observed in normal posterior lower lung was 0.804±0.230 (41% greater than the mean SUV in the anterior upper lung), which is in the range of the apparent SUV for a 5-mm lung lesion, with higher SUV, due to recovery coefficient issues. Thus this phenomenon could contribute to occasional false-negative lesions in those areas. Increased blood flow and FDG delivery and also scatter from heart and liver may contribute to the increased lower lung background activity. Regional differences in normal lung FDG uptake are significant and should be considered when interpreting pulmonary PET studies in patients with suspected primary or metastatic lung cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46841/1/259_2004_Article_BF00833385.pd

Achieving LDL cholesterol target levels <1.81 mmol/L may provide extra cardiovascular protection in patients at high risk: Exploratory analysis of the Standard Versus Intensive Statin Therapy for Patients with Hypercholesterolaemia and Diabetic Retinopathy study

Aims To assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension-to-treat population, intensive therapy [targeting LDL cholesterol = 2.59 to = 100 to = 2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy