Search PubMed⌕ Search

Biomedical subjects

Y Aoki

Publications and source records attributed to Y Aoki.

At least 325 records · Page 18Linked to original sources
PubMed1997

[High-dose conformal radiotherapy for glioblastoma multiforme].

The purpose of this study was to evaluate the impact of administering high doses by rotational multi-leaf collimator (MLC) conformal radiation therapy. From 1984 to 1995, thirty-five consecutive cases with glioblastoma multiforme were treated using rotational MLC conformal therapy. There were 23 men and 12 women, with an average age of 45 years (12-73 years). Median Karnofsky performance score was 80(30-100). Median tumor volume was 56 cc (8-800 cc). All patients underwent surgical intervention (only biopsy in one, partial resection in 13, subtotal resection in 18, and gross total resection in three). Radiation dose ranged from 60 to 80 Gy (mean 68.5 Gy) in 21 patients treated before 1991, and was 90 Gy in the 14 patients treated thereafter. Biweekly intravenous chemotherapy was also administered in both arms. The 1-year, 2-year, and 5-year survival rates were 72%, 43%, and 21%, respectively. Residual tumor volume was the only statistically significant factor for survival by multivariable analysis. The five-year survival rate of patients with residual tumors 2 cm or less in diameter was as high as 44%. Local failure was observed in 15 of the 18 patients in the lower dose group, whereas it was observed in only 4 of the 10 patients in the higher dose group. The difference was statistically significant. Rotational conformal therapy in combination with intensive surgical resection showed a favorable outcome. However, increased dose did not lead to higher survival rate.

Adult↗
PubMed1997

[Clinical evaluation of 2-mg granisetron tablet for nausea and vomiting induced by anticancer drugs including cisplatin].

The antiemetic effects on nausea and vomiting induced by anticancer drugs and safety of a 2-mg granisetron tablet were studied in cancer patients, particularly in the field of gynecology, who had been treated with anticancer drugs including cisplatin (CDDP) at 50 mg/m2 or more. The 1-mg granisetron tablet is already commercially available and used widely in clinical practice by oral administration of two tablets per dosage. In this investigation, the clinical efficacy, safety and usefulness of a 2-mg tablet, which can be taken more easily, were studied. The 2-mg granisetron tablet was judged to be "remarkably effective" or "effective" for nausea and vomiting in 22 (66.7%) of 33 patients. For safety, neither adverse experiences nor abnormal laboratory values were judged to be of clinical significance. The 2-mg granisetron tablet was considered "extremely useful" or "useful" in 22 (66.7%) of 33 patients. The above results confirmed the excellent antiemetic effect on nausea and vomiting induced by anticancer drugs including CDDP and the high degree of safety of a 2-mg granisetron tablet.

Adult↗
PubMed1997

[Analysis of IL-8 gene transcription in human bronchial epithelial cells by stable transfection of a reporter gene].

Transcriptional activation of the expression of the gene for interleukin (IL)-8) in airway epithelial cells was analyzed by stable transfection of human bronchial epithelial cells (16 HBE) with a reporter plasmid pIL-8/Luc, which the expression of luciferase reporter gene is driven by human IL-8 promoter. As compared with the resting condition, the luciferase activity was 3.9 times higher after stimulation with phorbol-myristate-acetate (20 ng/ml), 1.6 times higher after stimulation with tumor necrosis factor-alpha (100 U/ml), and 2.7 times higher after stimulation with interleukin-1 beta (100 U/ml). Dexamethasone inhibited the effects of these stimulants by 10 to 50 percent. These results closely correspond to those of IL-8 mRNA analyses with Northern blotting and IL-8 protein analyses done by enzyme-linked immunosorbent assay. The transgenic cell line IL-8 Luc/16HBE can also be used in screening for drug effects, and may be useful for quantifying IL-8 inducibility in clinical samples obtained from the lungs.

Bronchi↗
PubMed1997

[Spreadsheets of a conventional application software for calculation of plausibility of paternity: application to parentage testing with highly polymorphic markers in deceased party].

We designed a spreadsheet package for the computation of plausibility of paternity, that can cope with highly polymorphic genetic markers and cases of deceased parties. The application program is Microsoft EXCEL, which is one of the best-selling spreadsheet software running on both Microsoft Windows and Macintosh OS. Komatsu's formula for paternity testing was mainly employed in the spreadsheet package. Probability of the mother-child-alleged father combination was calculated using "IF" function to compare the members' genotypes, whereas "VLOOKUP (or HLOOKUP)" function was employed to refer to a list of genes and their frequencies. In case of a phenotype consisting of several genotypes, the list of phenotypes versus genotypes was also given, to which the function referred. To extend these spreadsheets available for the test of deceased party, additional sheets were also created to estimate frequencies of alleged father's possible genotypes. These probabilities were calculated on the basis of types of his parents and siblings, those of his wife and their biological children, and those of both. This package would be cut out to compute the probability of paternity with extremely polymorphic loci with gentle user interface. Calculation time is satisfactorily short, although it requires considerably large disk space in some extremely complicated cases. Japanese version of this package is freely available at anonymous FTP site of the Department of Forensic Medicine, Tohoku University School of Medicine.

Female↗
PubMed1997

[Correlates and prognosis in relation to intellectual dysfunction in a community-residing elderly population].

To estimate the risk factors for intellectual dysfunction and examine its prognosis in a community-residing (non-institutionalized) elderly population, a randomly selected sample of 1,473 elderly people aged 65 years and over living in S city, Osaka Prefecture, was studied in October 1992, and data were obtained from 1,383, a response rate of 93.9%. A cohort of 1,383 was followed for 42 months and follow-up was completed for 1,300 (94.0%). The main results were as follows: 1) The prevalence of intellectual dysfunction did not differ significantly between sexes, and there was an increasing prevalence of intellectual dysfunction with age in both sexes. The prevalence of severe intellectual dysfunction was found to increase highly at age 85 and over. 2) By univariate analysis, odds ratios for age older than 75 years, low Activities of Daily Living (ADL), urinary and fecal incontinence, and no participation in social activities were significantly higher than 1 in any level of mild, moderate, and severe intellectual dysfunction. In the multivariate analysis using logistic regression, age older than 75 years and urinary and fecal incontinence showed significant higher odds ratios than 1 for severe intellectual dysfunction, and low ADL and treatment for hypertension also showed significant higher odds ratios than 1 for moderate intellectual dysfunction. 3) From analysis using the Kaplan-Meier method, the cumulative survival rates decreased with a decline in intellectual functioning in both age groups of 65-74 and 75 years and older. 4) Application of the Cox proportional hazards model resulted in adjusted hazard ratio for severe intellectual dysfunction of 1.79 (95% confidence interval, 1.02-3.12), controlling for other factors such as sex, age, general health status, incontinence and social activities.

Activities of Daily Living↗
PubMed1996

Change in ascorbate radical production in an irradiated experimental tumor with increased tumor size.

We have reported that ascorbate radical (Asc.-) could serve as an indicator of the amount of hydroxyl radical and superoxide produced by irradiation in vivo. Using this method, we investigated the relationship between tumor size and Asc.- production after irradiation (10 Gy) and between tumor size and the radical-scavenging ability of WR-2721 (300 mg/kg). Asc.- was measured in normal muscle and SCC-VII tumors transplanted into mice (n = 6). In tumors, the increase in Asc.- significantly decreased with increasing tumor size (r = -0.483; P < 0.05). The increase in Asc.- production after irradiation was more inhibited by WR-2721 in normal muscle tissue than in tumor tissue at various sizes. In tumors, the increase in Asc.- was less inhibited by WR-2721 with increasing tumor size. These results demonstrate that the increase in radical production after irradiation and drug distribution decreased with increasing tumor size and that WR-2721 has excellent differential protection. This method is expected to measure changes in the amounts of local hydroxyl radical and superoxide modified by a change of tumor environment or drug administration.

Amifostine↗
PubMed1996

IGF2 but not H19 shows loss of imprinting in human glioma.

Genomic imprinting is a gamete-specific modification resulting in the allele-specific expression of genes in somatic cells. A loss of imprinting (LOI) has been found in many embryonal and adult tumors, suggesting that it plays a role in tumor development. The incidence of LOI, however, does not seem to be ubiquitous among tumors because neuroblastoma and colorectal cancer revealed no LOI. We examined the involvement of LOI of IGF2 and H19 genes in human gliomas. The two genes were imprinted in normal brain subcortex tissues. In glioma, 8 of 14 informative cases (57%) revealed LOI in IGF2. The frequency did not depend on the tumor grade. For H19, in contrast, all 13 informative cases maintained imprinting. These results suggest that LOI of IGF2 but not H19 plays a role in the development of human glioma.

Adult↗
PubMed1996

Characterization of mutations induced by 300 and 320 nm UV radiation in a rat fibroblast cell line.

The cytotoxic and mutagenic activities of monochromatic ultraviolet light (UV) at four wavelengths (254, 290, 300 and 320 nm) were determined using a rat fibroblast cell line CREF stably infected with a retroviral vector carrying the neo and HSV-tk markers. In this system, mutations can be positively detected as acyclovir-resistant colonies. Although the action spectra for these activities closely fit some of the previously reported spectra for photochemical DNA modifications, erythema, cell killing and mouse skin carcinogenesis, they diverge at 320 nm from the absorption spectrum for DNA and the action spectrum for bacterial inactivation and mutagenesis. Structural comparison of the HSV-tk mutants detected after irradiation with 300 and 320 nm UV revealed (1) CC dimers and C oligomers as predominant targets at both wavelengths; (2) increased incidence of relatively large deletions at 300 nm; and (3) greatly increased frequency of tandem double mutations at both wavelengths and of clustered multiple mutations at 320 nm. These results suggest the involvement of distinct mechanisms specifically operating, or becoming evident, in UV-mediated mutagenesis at these different wavelengths in mammalian cells.

Acyclovir↗
PubMed1996

Cloning and functional expression of a cDNA encoding a mouse type 2 neuropeptide Y receptor.

A cDNA clone homologous with the human neuropeptide Y (NPY)-Y2 receptor has been isolated from a mouse brain cDNA library. Analysis of the predicted amino-acid sequence indicates that the polypeptide encoded by this cDNA is 94% homologous to the human NPY-Y2 receptor. In Chinese hamster ovary (CHO) cells expressing the mouse NPY-Y2 receptor, an increase in intracellular Ca2+ and inhibition of forskolin-induced cAMP accumulation were observed due to stimulation with NPY, NPY-(13-36) and peptide YY, but not with pancreatic polypeptide or [Leu31, Pro34]NPY. The fact that the NPY-induced increase in intracellular Ca2+ and inhibition of forskolin-induced cAMP accumulation were eliminated by pretreatment with pertussis toxin suggests that the NPY-Y2 receptor couples to PTX-sensitive G-protein(s), probably Gi/Go, in CHO cells.

Amino Acid Sequence↗
PubMed1996

Enzymatic diagnosis of holocarboxylase synthetase deficiency using apo-carboxyl carrier protein as a substrate.

We developed a simple and sensitive method for assessing holocarboxylase synthetase (HCS) activity that is based on measuring incorporation of [3H]biotin into apo-carboxyl carrier protein, a subunit of acetyl-CoA carboxylase from E. coli. Kinetic analysis of HCS from normal fibroblasts showed that the Km for biotin was 260 +/- 94 nmol/l (mean +/- S.D.; n = 5). In contrast, the Km values of HCS from two cell lines derived from patients with HCS deficiency were 7200 and 3700, clearly distinguishable from the control value. The sensitivity of this assay was so high that we were able to characterize a mutant enzyme whose activity had not been previously detected. Our method is useful for enzymatic diagnosis of HCS deficiency and characterization of HCS.

Acetyl-CoA Carboxylase↗
PubMed1996

Alterations of c-fos gene methylation in the processes of aging and tumorigenesis in human liver.

The state of DNA methylation in the c-fos gene was examined in human livers of different ages, cirrhosis and hepatocellular carcinoma. The degree of methylation in the intron 1 to exon 4 region increased with age, whereas all of the 10 cirrhosis samples revealed a decrease in methylation when compared to normal livers of similar ages. The 11 hepatocellular carcinomas showed varied alterations suggesting that the alteration of the c-fos gene methylation is related to aging as well as to early-step of hepatocarcinogenesis.

Adolescent↗
PubMed1996

Functional coupling of adenosine A2a receptor to inhibition of the mitogen-activated protein kinase cascade in Chinese hamster ovary cells.

Activation of Gs-coupled receptors enhances the increase in cyclic AMP mediated by adenylate cyclases. As it has been shown that cyclic AMP inhibits the epidermal growth factor-activated mitogen-activated protein kinase (MAPK) signalling pathway, stimulation of Gs-coupled receptors may lead to the inhibition of MAPK activation. To investigate the effect of a Gs-coupled receptor on the MAPK cascade, we cloned the adenosine (Ado) A2a receptor from a guinea-pig leucocyte cDNA library, and established Chinese hamster ovary (CHO) cells stably expressing the receptor (CHOAdoA2R). The [3H]5'-N-ethylcarbamoyladenosine (NECA) binding characteristics (Kd = 91.0 +/- 5.4 nM, Bmax = 707 +/- 11 fmol/mg of protein, n = 3) and NECA-induced cyclic AMP production indicate that the cloned Ado A2a receptor was functionally expressed in the cells. In CHO cells, thrombin induced intracellular Ca2+ increase and MAPK activation through the intrinsic G-coupled receptor. In CHOAdoA2R cells, NECA partially inhibited thrombin-elicited MAPK activation. When combining NECA-treatment with 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid acetoxymethyl ester (BAPTA-AM) loading, a nearly complete inhibition of the MAPK activation occurred. Forskolin also partially inhibited the MAPK activation and synergized with BAPTA-AM, suggesting that partial inhibition of MAPK activation by NECA results from cyclic AMP production via Ado A2a receptor activation. The same synergism of MAPK inhibition between wortmannin and BAPTA-AM was observed, but not between wortmannin and NECA. These results suggest that cyclic AMP production through Ado A2a receptor inhibits thrombin-elicited MAPK activation by a Ca(2+)-independent/wortmannin-sensitive pathway in CHO cells.

Adenosine↗
PubMed1996

Phosphorylation of c-Jun stimulated in primary cultured rat liver parenchymal cells by a coplanar polychlorinated biphenyl.

Phosphorylation of c-Jun was stimulated in primary cultured rat liver parenchymal cells by treatment with a coplanar polychlorinated biphenyl congener, 3,3'4,4'5-pentachlorobiphenyl (PenCB), as well as by epidermal growth factor, but was not stimulated by the non-coplanar form. However, the amount of c-Jun mRNA did not increase with PenCB treatment. PenCB may activate a signal-transducing pathway consisting of protein kinases.

Animals↗
PubMed1996

Induction of IL-6 production by bone marrow stromal cells on the adhesion of IL-6-dependent hematopoietic cells.

Cellular interactions between hematopoietic cells and stromal cells play crucial roles in the proliferation and differentiation of the hematopoietic cells. Interleukin-6 (IL-6)-dependent 7TD1 cells markedly proliferated without IL-6 when they were co-cultured with hematopoietic-supportive bone marrow stromal cells, HESS-5 cells and HESS-1 CL.3 cells, which can support long-term hematopoiesis in vitro with but not without direct cell contact, cell contact being prevented with a microporous membrane. The production of IL-6 and the amount of IL-6 mRNA in hematopoietic-supportive stromal cells but not 7TD1 cells significantly increased only when the stromal cells were co-cultured in direct contact with 7TD1 cells. Furthermore, the amount of IL-6 mRNA increased according to the number of 7TD1 cells co-cultured. These inductions were not observed on co-culture with a murine myeloid cell line, M1 cells, or on the addition of the co-culture supernatant. These results suggest that 7TD1 cells transmit the signal to stromal cells that enhances IL-6 production by stromal cells via direct cell contact. A certain specific molecule for transduction of the signals may exist on the surface membrane of stromal cells and hematopoietic cells.

Animals↗
PubMed1996

Alteration of c-fos gene methylation in human gliomas.

In an attempt to find a common DNA alteration occurring in human glioma, we examined DNA methylation in 34 gliomas of various pathological grades and compared them with those in normal cerebral subcortex DNA. The total methylated cytosine levels in the genome did not differ appreciably between the tumors and the normal tissues; however, the degree of DNA methylation in several proto-oncogenes and suppressor oncogenes showed some alterations. Among them, the c-fos gene demonstrated deviation from that of normal tissues in all cases examined, suggesting that the alteration of c-fos gene methylation plays a role in the early steps of human glioma development.

Adult↗
PubMed1996

Recurrent placental site trophoblastic tumor of the uterus: clinical, pathologic, ultrastructural, and DNA fingerprint study.

Placental site trophoblastic tumor is a rare disease. Most benign cases of this disease show a few mitotic figures of the tumor while recurrent cases usually have more than 5 mitoses per 10 high-power fields. The present case was primarily treated by hysterectomy and chemotherapy and had 2 mitoses in 10 high-power fields. After 1 years and 4 months of therapy the patients was diagnosed as ovarian metastasis because of gradually increasing serum beta-human chorionic gonadotropin (hCG) level and abnormally high fluid levels of beta-hCG and human placental lactogen (hPL) punctured from her cystic ovarian tumor. This recurrent case was further treated with another regimen of chemotherapy for 7 courses, and the serum beta-hCG level had decreased at present. This report describes the recurrent case and discusses the histology of a few mitotic figures, electron microscopic findings, and results of the DNA fingerprint analysis of the primary tumor.

Adult↗