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Biomedical subjects

A Asai

Publications and source records attributed to A Asai.

At least 19 recordsLinked to original sources
PubMed2006

How do bioethics teachers in Japan cope with ethical disagreement among healthcare university students in the classroom? A survey on educators in charge.

OBJECTIVE: The purpose of this study was to demonstrate how educators involved in the teaching of bioethics to healthcare university students in Japan would cope with ethical disagreement in the classroom, and to identify factors influencing them. METHODS: A cross sectional survey was conducted using self administered questionnaires mailed to a sample of university faculty in charge of bioethics curriculum for university healthcare students. RESULTS: A total of 107 usable questionnaires were returned: a response rate of 61.5%. When facing ethical disagreement in the classroom, coping behaviour differed depending on the topic of discussion, was influenced by educators' individual clear ethical attitudes regarding the topic of discussion, and was independent of many respondents' individual and social backgrounds. Among educators, it was commonly recognised that the purpose of bioethics education was to raise the level of awareness of ethical problems, to provide information about and knowledge of those issues, to raise students' sensitivity to ethical problems, and to teach students methods of reasoning and logical argument. Yet, despite this, several respondents considered the purpose of bioethics education to be to influence students about normative ethical judgments. There was no clear relationship, however, between ways of coping with ethical disagreement and educators' sense of the purpose of bioethics education. CONCLUSIONS: This descriptive study suggests that educators involved in bioethics education for healthcare university students in Japan coped in various ways with ethical disagreement. Further research concerning ethical disagreement in educational settings is needed to provide better bioethics education for healthcare students.

Adaptation, Psychological↗
PubMed2002

Co-transduction of Apaf-1 and caspase-9 highly enhances p53-mediated apoptosis in gliomas.

Mutation of the p53 gene plays a critical role in the development of cancer and response to cancer therapy. To analyze the mechanism of cancer development and to improve cancer therapy, it is important to assess which genes are downstream components of p53 in cancers, and whether the expression levels of these genes affect p53-mediated apoptosis. In this study, we transduced the wild type p53 gene along with the Apaf-1 and caspase-9 genes via adenovirus vectors into U251 and U-373MG glioma cells harbouring a mutated p53, and evaluated the degree of apoptosis. Co-induction of Apaf-1 and caspase-9 genes highly enhanced p53-mediated apoptosis in glioma cells. Induction of wild type p53 enhanced the expression levels of Bax, p21/WAF1, and Fas protein. To determine which gene is activated by wild type p53 induction and, in turn, activates Apaf-1 and caspase-9, we transduced the Bax, p21/WAF1 or Fas gene via adenovirus vector to U251 cells to achieve a similar expression level as that induced by the Adv for p53 in U251 cells. U251 cells transduced with Fas concomitant with the Apaf-1 and caspase-9 genes underwent drastic apoptosis. This suggests that induction of wild type p53 upregulates Fas, which in turn may play a role in the activation of Apaf-1 and caspase-9. These results are important for analyzing the mechanism of tumour development and for predicting the therapeutic effect of p53 replacement gene therapy in a particular patient.

Adenoviridae↗
PubMed2001

Menstrual and reproductive factors for subarachnoid hemorrhage risk in women: a case-control study in nagoya, Japan.

BACKGROUND AND PURPOSE: We sought to examine the relationship between menstrual and reproductive factors and the risk of subarachnoid hemorrhage (SAH), using a case-control study. METHODS: Cases consisted of a consecutive series of 124 women patients with first spontaneous SAH aged 30 to 79 years and confirmed aneurysm(s) by angiography and/or CT scan. Hospital and community controls subjects were identified, matched to each case by age (+/-2 years). RESULTS: Increased SAH risk was associated with (1) earlier age at menarche (adjusted odds ratio [OR]=3.24 for age <13 years compared with age >/=13 years; 95% CI, 1.25 to 4.03) and (2) nulligravidity (adjusted OR=4.23; 95% CI, 1.05 to 7.56). No significant association of SAH risk was found with regularity of menstrual cycle, age at pregnancy, age at first birth, and number of births. The greatest risk was for the combined effect of nulligravidity and earlier menarche (<13 years) (adjusted OR=6.37; 95% CI, 1.12 to 36.2). CONCLUSIONS: The combined effect of several variables related to menstrual and reproductive history may exert a greater influence on risk of SAH compared with a single menstrual or reproductive variable.

Adult↗
PubMed2001

Over-expression of APAF-1 and caspase-9 augments radiation-induced apoptosis in U-373MG glioma cells.

The p53 tumor-suppressor gene plays a critical role in radiation-induced apoptosis. Several genes, including Bax and Fas, are involved in p53-mediated apoptosis, and their over-expression enhances the degree of radiation-induced apoptosis. Apaf-1 and caspase-9 have been reported to be downstream components of p53-mediated apoptosis, suggesting that these genes play a role in radiation-induced apoptosis. In this study, we transduced U-373MG cells harboring mutant p53 with the Apaf-1 and/or caspase-9 genes via adenoviral (Adv) vectors concomitant with X-ray irradiation and evaluated the degree of apoptosis. The percentage of apoptotic cells in U-373MG cells co-infected with the Adv for Apaf-1 (Adv-APAF-1) and that for caspase-9 (Adv-Casp9) and treated with irradiation (24%) was much higher than that in cells co-infected with Adv-APAF-1 and Adv-Casp9 and not treated with irradiation (0.86%) and that in cells infected with either Adv-APAF-1 or Adv-Casp9 and treated with irradiation (2.0% or 2.6%, respectively). The apoptosis induced by co-transduction of Apaf-1 and caspase-9 and irradiation was repressed in cells that were co-infected with the Adv for Bcl-X(L) but not in cells co-infected with the Adv for Bcl-2. These results indicate that Apaf-1 and caspase-9 play a role in radiation-induced apoptosis in cancer cells harboring mutant p53. Bcl-X(L) may be critically involved in the radioresistance of cancer cells by repressing Apaf-1- and caspase-9-mediated apoptosis. Expression of Apaf-1 and caspase-9 in tumors may be an important determinant of the therapeutic effect of irradiation in cancer treatment.

Adenoviridae↗
PubMed2001

Adenovirus-mediated transfer of p53 augments hyperthermia-induced apoptosis in U251 glioma cells.

PURPOSE: Hyperthermia kills glioma cells by inducing apoptosis and is thereby an effective therapeutic modality for the treatment of malignant gliomas. However, cells harboring mutated p53 are refractory to hyperthermia-induced apoptosis. In this study, we assessed whether or not adenovirus (Adv)-mediated transduction of p53 overrides this resistant mechanism. METHODS AND MATERIALS: We transduced the p53 wild-type tumor suppressor gene into U251 glioma cells harboring mutated p53 using Adv vectors in combination with hyperthermia (43, 44.5 degrees C), and evaluated the degree of cell death and apoptosis. RESULTS: The percentage of cells that had died, as measured by trypan blue staining, among U251 cells infected with the Adv for p53 (Adv-p53) and treated with hyperthermia, was significantly higher than the percentage of cells that had died among U251 cells infected with Adv-p53 and not treated with hyperthermia, or those infected with the control Adv for dE (Adv-dE) and treated with hyperthermia. The degree of apoptosis, measured at 24 h after treatment, in hyperthermia-treated U251 cells infected with Adv-p53 (43 degrees C, 73%; 44.5 degrees C, 92%) was much higher than that infected with Adv-p53 (41%), or that infected with control Adv-dE and treated with hyperthermia (43 degrees C, 1.3%; 44.5 degrees C, 19%). Treatment with combined hyperthermia and Adv-p53 infection induced cleavage of caspase-3 in U251 cells. CONCLUSION: These results indicate that Adv-mediated transduction of p53 would render glioma cells highly sensitive to hyperthermia.

Adenoviridae↗
PubMed2001

Expression of smooth muscle proteins in cavernous and arteriovenous malformations.

Cavernous malformations (CVMs) and arteriovenous malformations (AVMs) were immunostained for three smooth muscle cell (SMC)-specific protein markers (smooth muscle alpha-actin, SM1 and SM2). Smooth muscle alpha-actin, a widely used marker of SMCs, is reportedly one of the earliest proteins expressed during differentiation of SMCs and expressed in some kinds of mesoderm-derived cells. In contrast, SM1, an isoform of myosin heavy chain (MHC), is detected only in SMCs. SM2 is another MHC isoform and expressed in the contractile phenotype of SMC. All 14 intraaxial CVMs were positive for smooth muscle alpha-actin, but SM1 was detected in only three of them and SM2 was not found. Their staining pattern resembled that of normal intraparenchymal and pial veins. All 15 cerebral AVMs and 5 out of 6 extraaxial CVMs from the cavernous sinus, orbit and scalp were positive for all three markers, as were the normal cerebral arteries. The venous components of AVMs, as well as the arterial components, expressed SM2, and were different from normal veins in the brain and intraaxial CVMs. This study shows that the histological analysis using the three markers for SMC is useful to differentiate intraaxial CVM from AVM and extraaxial CVMs.

Actins↗
PubMed2001

Tumour suppressor activity of human imprinted gene PEG3 in a glioma cell line.

BACKGROUND: Mouse imprinted gene Peg3 encodes a large C2H2 type zinc finger protein with unique characteristics. Peg3 knockout mice were found to show an impairment in maternal behaviour of the adult female. Mouse Peg3 is located on the proximal region of chromosome 7 which is syntenic to the long arm of human chromosome 19. It has been reported that a loss of heterozygosity (LOH) of chromosome 19q occurs frequently in several glioma types. RESULTS: We isolated human PEG3 cDNA. Both human and mouse PEG3 were strongly expressed in the adult brain and the Peg3 protein was localized in the nuclei of both neurones and glial cells. A significant decrease in PEG3 expression was more commonly observed in glioma cell lines as compared with that in primary cultures of astrocytes. Transfection of PEG3 cDNA in a glioma cell line resulted in a loss of tumorigenicity in nude mice. CONCLUSIONS: The human PEG3 gene is a paternally expressed imprinted gene. Introduction of PEG3 cDNA into the glioma cells suggests that human PEG3 protein functions as a tumour suppressor. Human PEG3 is located on 19q13.4 and is one of the candidates for tumour suppressor genes that are predicted to be sited in gliomas.

5' Untranslated Regions↗
PubMed2001

Dialysis patients' preferences regarding cardiopulmonary resuscitation and withdrawal of dialysis in Japan.

The aim of this study is to show the preferences of Japanese dialysis patients for receiving cardiopulmonary resuscitation (CPR) in their current health status, if they were severely demented, or if they had terminal cancer and to determine their desires about continuing dialysis if they were severely demented or had terminal cancer. A questionnaire survey including the three scenarios was administered to 450 dialysis patients in 15 hospitals in JAPAN: Three hundred ninety-eight patients completed the questionnaires for a response rate of 88%. The majority of responding patients were men and were undergoing hemodialysis. Only 5% of the patients had discussed their preferences regarding CPR with their physicians, and 29%, with their family members. Forty-two percent of the patients answered that they would want to receive CPR if they experienced cardiopulmonary arrest in their current health status, and 12% answered in the affirmative if they were seriously demented or had terminal cancer. Eighteen percent of the patients would want to continue dialysis if they were demented, and 45%, if they had terminal cancer. Statistical analysis showed that more patients who were working tended to want to continue dialysis if they had terminal cancer than those who were not (53% versus 37%; P < 0.014). Patients' age and preferences did not statistically correlate. Preferences of Japanese dialysis patients for CPR and dialysis vary according to differences in health status, and only a minority would want to receive CPR for cardiopulmonary arrest even in their current health status.

Adult↗
PubMed2001

Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue.

Curcumin and its structurally related compounds (curcuminoids), the phenolic yellowish pigments of turmeric, display antioxidative, anticarcinogenic and hypocholesterolemic activities. In this study, we investigated the effects of dietary supplemented curcuminoids [commercial grade curcumin: a mixture of curcumin (73.4%), demethoxycurcumin (16.1%) and bisdemethoxycurcumin (10.5%)] on lipid metabolism in rats. Male Sprague-Dawley rats were assigned to three diet groups (n = 6) and fed a moderately high-fat diet (15 g soybean oil/100 g diet) for 2 wk. One diet group did not receive supplements (CONT), while the others were supplemented with 0.2 g curcuminoids/100 g diet (CUR0.2) or 1.0 g curcuminoids/100 g diet (CUR1.0). Liver triacylglycerol and cholesterol concentrations were significantly lower in CUR1.0 rats than in CONT rats. Plasma triacylglycerols in the VLDL fraction were also lower in CUR1.0 rats than in CONT rats (P < 0.05). Hepatic acyl-CoA oxidase activity of both the CUR0.2 and CUR1.0 rats was significantly higher than that of CONT rats. Furthermore, epididymal adipose tissue weight was significantly reduced with curcuminoid intake in a dose-dependent manner. These results indicate that dietary curcuminoids have lipid-lowering potency in vivo, probably due to alterations in fatty acid metabolism.

Adipose Tissue↗
PubMed2001

Caspase-9 transduction overrides the resistance mechanism against p53-mediated apoptosis in U-87MG glioma cells.

OBJECTIVE: Conflicting reports have been published with regard to the relationship between the efficacy of p53 gene therapy and the p53 status of gliomas. In this study, we evaluated whether U-87MG glioma cells harboring wild-type p53 and U251 and U-373MG glioma cells harboring mutated p53 demonstrate different sensitivities to p53-induced apoptosis. In addition, we tested whether transduction of Bax or caspase-9, which are downstream components of p53-induced apoptosis, can override the resistance mechanism of U-87MG cells to apoptosis. METHODS: We transduced U-87MG, U251, and U-373MG glioma cells with p53, Bax, or caspase-9 genes via adenovirus (Adv) vectors, to induce the same level of respective proteins, and evaluated the degree of apoptosis. RESULTS: U-87MG cells were highly resistant to Adv for p53 (Adv-p53)-mediated apoptosis, whereas U251 and U-373 cells underwent extensive apoptosis after Adv-p53 infection. In U-87MG cells, the elevation of Bax and Fas was not as marked as that observed in U251 and U-373MG cells after Adv-p53 infection. Endogenous expression of Bcl-XL and Bcl-2 in U-87MG cells was greater than that in U251 and U-373MG cells. U-87MG cells were more resistant to Bax-mediated apoptosis than were U251 or U-373MG cells. In contrast, U-87MG cells were more sensitive to caspase-9-mediated apoptosis than were U251 or U-373MG cells, suggesting that transduction of caspase-9 may override the resistance mechanism of U-87MG to p53-mediated apoptosis. CONCLUSION: These results demonstrate that proapoptotic function induced by p53 transduction in U-87MG cells was repressed at several steps and that induction of caspase-9 may circumvent this resistance mechanism.

Apoptosis↗
PubMed2001

Co-transduction of Apaf-1 and caspase-9 augments etoposide-induced apoptosis in U-373MG glioma cells.

Several apoptosis-related genes have been reported to be involved in chemotherapy-induced apoptosis in cancers. An assessment of the relationship between expression of those genes and the degree of chemotherapy-induced apoptosis may be useful in improving the efficacy of cancer therapy. We transduced Apaf-1 (apoptotic protease-activating factor-1) and caspase-9 into U-373MG glioma cells using adenovirus (Adv) vectors in the presence of etoposide and evaluated the degree of apoptosis. The degree of apoptosis in etoposide-treated U-373MG cells infected with Adv for Apaf-1 (Adv-APAF1) was higher (27%) than that in cells infected with control Adv (14%), that in cells infected with Adv for caspase-9 (Adv-Casp9) was higher (34%) than that in cells infected with Adv-APAF1, and that in cells infected with both Adv-APAF1 and Adv-Casp9 was the highest (41%). Treatment with etoposide increased expression of p53 and decreased expression of Bcl-X(L) in U-373MG cells which harbored mutant p53. These results indicate that the expression of Apaf-1 and caspase-9 may be important determinants in predicting the sensitivity of cancers to chemotherapy. Adv-mediated co-transduction of Apaf-1 and caspase-9 should render cancer cells highly sensitive to chemotherapy.

Adenoviridae↗
PubMed2001

Doctors' and nurses' attitudes towards and experiences of voluntary euthanasia: survey of members of the Japanese Association of Palliative Medicine.

OBJECTIVE: To demonstrate Japanese doctors' and nurses' attitudes towards and practices of voluntary euthanasia (VE) and to compare their attitudes and practices in this regard. DESIGN: Postal survey, conducted between October and December 1999, using a self-administered questionnaire. PARTCIPANTS: All doctor members and nurse members of the Japanese Association of Palliative Medicine. MAIN OUTCOME MEASURE: Doctors' and nurses' attitude towards and practices of VE. RESULTS: We received 366 completed questionnaires from 642 doctors surveyed (response rate, 58%) and 145 from 217 nurses surveyed (68%). A total of 54% (95% confidence interval (CI): 49-59) of the responding doctors and 53% (CI: 45-61) of the responding nurses had been asked by patients to hasten death, of whom 5% (CI: 2-8) of the former and none of the latter had taken active steps to bring about death. Although 88% (CI: 83-92) of the doctors and 85% (CI: 77-93) of the nurses answered that a patient's request to hasten death can sometimes be rational, only 33% (CI: 28-38) and 23% (CI: 16-30) respectively regarded VE as ethically right and 22% (CI: 18-36) and 15% (CI: 8-20) respectively would practise VE if it were legal. Logistic regression model analysis showed that the respondents' profession was not a statistically independent factor predicting his or her response to any question regarding attitudes towards VE. CONCLUSIONS: A minority of responding doctors and nurses thought VE was ethically or legally acceptable. There seems no significant difference in attitudes towards VE between the doctors and nurses. However, only doctors had practised VE.

Attitude of Health Personnel↗
PubMed2001

Radiation-induced apoptosis of oligodendrocytes in the adult rat brain.

Although radiation injuries to the brain are well documented, immediate early histological changes in the brain remain to be defined. The present study characterizes glial injury provoked in adult rat white matter within 24 h after a single irradiation of the whole brain (10 or 20 Gray). Irradiated brains were histologically and histochemically analyzed. TUNEL-positive cells exhibiting apoptotic morphology were counted in five representative regions of the white matter. Glial cell death was further evaluated by glial cell density 24 h after irradiation, which induced both dose (p < 0.0001)- and time- (p < 0.0001) dependent apoptosis in these cells. The overall apoptotic rate in the white matter peaked within 8 h after irradiation. Total glial cell density decreased significantly in the white matter 24 h after irradiation. TUNEL-positive cells were immunohistochemically negative for GFAP, a marker for astrocytes, but positive for CNP, a marker for oligodendrocytes. The apoptotic rate was highest in the external capsule (p < 0.0001), followed by the fimbria and genu of the corpus callosum (p < 0.0001). The rates were lowest in the internal capsule and cerebellum. These data indicated that brain irradiation induces rapid apoptotic depletion of the oligodendroglial population, which may participate in the development of radiation-induced pathological conditions.

Age Factors↗
PubMed2000

Degree of apoptosis induced by adenovirus-mediated transduction of p53 or p73alpha depends on the p53 status of glioma cells.

It has been reported that U-87MG glioma cells with wild-type p53 are resistant to p53 replacement gene therapy. As some gliomas harbor wild-type p53, it would be important to override the resistance mechanism due to wild-type p53 in glioma gene therapy. In this study, we transduced U-87MG cells or U251 glioma cells harboring mutated p53 with the p53 or p73alpha gene (a homologue of p53, that differently induces some p53-responsive genes) via adenovirus vectors (Advs) at same multiplicities of infection (MOIs) into respective cells (U-87MG: MOI 1000, U251: MOI 100), and evaluated the degree of apoptosis. The results demonstrate that the degree of apoptosis induced by Adv-mediated transduction of p53 in U-87MG cells was lower than that in U251 cells, whereas that induced by Adv-mediated transduction of p73alpha in U-87MG cells was higher than that in U251 cells. Bax expression in U-87MG and U251 cells induced by Adv-mediated transduction of p53 was almost the same as that of p73alpha. On the other hand, Adv-mediated transduction of p73alpha induced caspase-9 at higher levels than that of p53 in both cells. The results indicate that Adv-mediated transduction of p73alpha might be beneficial to overcome the resistance mechanism of glioma cells harboring wild-type p53.

Adenoviridae↗
PubMed2000

Occurrence of orally administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma.

Curcuminoids, curcumin and its structurally related compounds, constitute the phenolic yellowish pigment of turmeric. We investigated the absorption and metabolism of orally administered curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) in rats. HPLC and LC-MS analyses after enzymatic hydrolyses showed that the predominant metabolites in plasma following administration were glucuronides and glucuronide/sulfates (conjugates with both glucuronide and sulfate) of curcuminoids. The plasma concentrations of conjugated curcuminoids reached a maximum one hour after administration. The conjugative enzyme activities for glucuronidation and sulfation of curcumin were found in liver, kidney and intestinal mucosa. These results indicate that orally administered curcuminoids are absorbed from the alimentary tract and present in the general blood circulation after largely being metabolized to the form of glucuronide and glucuronide/sulfate conjugates.

Administration, Oral↗
PubMed2000

Changes in the apparent diffusion coefficient of water and T2 relaxation time in gerbil hippocampus after mild ischemia.

Selective neuronal death of the hippocampal CA1 area after mild ischemia is known as delayed neuronal death (DND). Progression of DND was evaluated using 7T MRI in gerbils. In the CA1, the T2 relaxation time started to increase on day 3 and was significantly higher on day 4 than that of the control gerbils. However, the apparent diffusion coefficient of water (ADC) was significantly lower on day 1 than in the control and continued to decline up to day 4. Changes in T2 coincided with loss of MAP2 immunoreactivity, while the ADC decrease preceded these changes. After 1 month, the ADC had returned to within the normal range, while T2 had decreased to below the control level. These results suggest that MRI is useful for monitoring DND.

Animals↗