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Biomedical subjects

A Asai

Publications and source records attributed to A Asai.

At least 73 records · Page 4Linked to original sources
PubMed1999

Increased sarcolemmal permeability in the cerebral artery during chronic spasm: an assessment using DNA-binding dyes and detection of apoptosis.

Alteration of sarcolemmal permeability was evaluated in the cerebral artery after subarachnoid hemorrhage. Significance of membrane dysfunction in the pathogenesis of chronic spasm and contribution of apoptosis were investigated in a canine model. Permeability of the smooth muscle cell (SMC) membrane was assessed by double staining with a hydrophilic (ethidium bromide [EB]) and a lipophilic (Hoechst 33342) DNA-binding dye. Quantitative observations were made with a ultraviolet-fluorescence microscope and a ultraviolet-laser confocal microscope. Occurrence of apoptosis was studied using electrophoresis and TUNEL method. In the normal arteries, nuclei of SMC were stained with Hoechst 33342 but not with EB. In the spastic arteries, SMC in the inner layer of the tunica media were stained with EB. The incidence of EB-positive cells reached maximum on day 7 (45 +/- 19%) and decreased in 2 to 4 weeks (13 +/- 5.2% and 5.0 +/- 2.1%, respectively), in parallel with amelioration of spasm. Electron and light microscopic observations revealed increased density of SMC cytoplasm with widening of the extracellular space. Necrosis was not evident. Apoptosis was not detected by the two methods. These results demonstrate that an augmentation in sarcolemmal permeability takes place during the course of chronic vasospasm and suggest its close correlation to pathogenesis.

Animals↗
PubMed1999

Survey of Japanese physicians' attitudes towards the care of adult patients in persistent vegetative state.

OBJECTIVES: Ethical issues have recently been raised regarding the appropriate care of patients in persistent vegetative state (PVS) in Japan. The purpose of our study is to study the attitudes and beliefs of Japanese physicians who have experience caring for patients in PVS. DESIGN AND SETTING: A postal questionnaire was sent to all 317 representative members of the Japan Society of Apoplexy working at university hospitals or designated teaching hospitals by the Ministry of Health and Welfare. The questionnaire asked subjects what they would recommend for three hypothetical vignettes that varied with respect to a PVS patient's previous wishes and the wishes of the family. RESULTS: The response rate was 65%. In the case of a PVS patient who had no previous expressed wishes and no family, 3% of the respondents would withdraw artificial nutrition and hydration (ANH) when the patient did not require any other life-sustaining treatments, 4% would discontinue ANH, and 30% would withhold antibiotics when the patient developed pneumonia. Significantly more respondents (17%) would withdraw ANH in the case of a PVS patient whose previous wishes and family agreed that all life support be discontinued. Most respondents thought that a patient's written advance directives would influence their decisions. Forty per cent of the respondents would want to have ANH stopped and 31% would not want antibiotics administered if they were in PVS. CONCLUSIONS: Japanese physicians tend not to withdraw ANH from PVS patients. Patients' written advance directives, however, would affect their decisions.

Adult↗
PubMed1999

Antioxidative effects of turmeric, rosemary and capsicum extracts on membrane phospholipid peroxidation and liver lipid metabolism in mice.

Phospholipid hydroperoxides (PLOOH) in the plasma, red blood cells (RBC) and liver of mice were measured after dietary supplementation for one week (1% w/w of diet) with a turmeric extract (curcuminoid), hexane extract of rosemary, and supercritical CO2-extracted capsicum pigment (supplemented with alpha-tocopherol to prevent fading). A lower PLOOH level was found in RBC of the spice extract-fed mice (65-74% of the non-supplemented control mice). The liver lipid peroxidizability induced with Fe2+/ascorbic acid was effectively suppressed by dietary supplementation with the turmeric and capsicum extracts to mice. While no difference in the plasma lipids was observed, the liver triacylglycerol concentration of the turmeric extract-fed mice was markedly reduced to one-half of the level in the control mice. These findings suggest that these spice extracts could act antioxidatively in vivo by food supplementation, and that the turmeric extract has the ability to prevent the deposition of triacylglycerols in the liver.

Animals↗
PubMed1998

Construction, propagation, and titer estimation of recombinant adenoviruses carrying proapoptotic genes.

Generation of a recombinant adenovirus (Adv) that induces the constitutive expression of an apoptotic gene has been extremely difficult owing to severe apoptotic damage to the host cell. In this study, 293 cells were transduced with the caspase-inhibiting CrmA gene (293-CrmA cells), and used as host cells to generate Adv carrying apoptosis-inducing genes (proapoptotic genes). The 293-CrmA cells proved to be highly efficient for the construction of recombinant Adv carrying genes encoding Fas and Fas ligand. Moreover, the 293-CrmA line produced an ample quantity of these recombinant viruses. Because the conventional 293 plaque formation assay did not reflect the actual number of cells infected with the Adv carrying the proapoptotic gene, a determination of the Adv DNA copy number introduced into target cells was necessary to evaluate the quantity of infective virus. The techniques described here should be widely applicable for the construction of a recombinant Adv, in ample quantity, and for the estimation of the quantity of recombinant Adv produced.

Adenoviridae↗
PubMed1998

Apoptosis by retrovirus- and adenovirus-mediated gene transfer of Fas ligand to glioma cells: implications for gene therapy.

Astrocytic tumors frequently express Fas/APO-1 (Fas), in sharp contrast to surrounding normal brain cells, providing a potential window through which selective killing of tumor cells could be pursued. To assess this possibility, we transduced Fas into U251, a glioma cell line resistant to anti-Fas antibody-mediated apoptosis, and obtained transfectants with high levels of Fas expression. Anti-Fas antibody showed significantly enhanced cytotoxicity for the transfectants, suggesting that U251 cells maintained an intercellular cascade of Fas-mediated apoptosis. When U251 transfectants with high-level Fas expression were transduced with Fas ligand-encoding gene via retrovirus, they were unaffected by exposure to anti-Fas antibody or Fas ligand adenovirus (Adeno-FL). Thus, retroviral induction of Fas ligand into the glioma cells with high levels of Fas led to the selection of cells that were resistant to Fas-dependent apoptosis. These resistant U251 transfectants were susceptible to FADD adenovirus (Adeno-FADD)-induced apoptosis, indicating that a cascade of death signals was blocked at the steps between Fas ligand and FADD. As for adenoviral transduction of Fas ligand into gliomas, gliomas with a relatively high level of expression of Fas were remarkably sensitive to Adeno-FL-induced apoptosis. Besides, Adeno-FADD induced pronounced apoptosis in all glioma cells. Our data suggest the possibility of using adenovirus-mediated transduction of Fas ligand and FADD genes as a therapeutic approach to target gliomas.

Adenoviridae↗
PubMed1998

Nedaplatin and 5-FU combined with radiation in the treatment for esophageal cancer.

A series of patients with esophageal cancer was treated with chemotherapeutic regimens of the new antitumor platinum preparation nedaplatin plus 5-FU in combination with radiation therapy, and the therapeutic responses, side effects, and complications were clinically assessed. There were 2 patients with a complete response and 11 patients with a partial response, hence, a response rate of 76.5%. Major adverse reactions were those of hematological toxicity and included leukopenia (13 patients, 76.5%), thrombocytopenia (8 patients, 47.1%), and lowered serum hemoglobin concentration (9 patients, 52.9%). The leukopenia and thrombocytopenia, though of a grade 3 severity in 3 and 2 patients, respectively, subsided spontaneously in all affected cases. Gastrointestinal adverse reactions were mild and included appetite loss in 7 patients (41.2%) and nausea in 2 patients (11.8%). The only abnormality in renal function observed was a slight elevation of serum creatinine in one patient. The combined therapy of chemotherapy with nedaplatin and 5-FU plus radiation produced a high response rate in the treatment of carcinoma of the esophagus and was associated with reduced gastrointestinal and renal toxicity. The results indicate the combined therapy with nedaplatin to be clinically useful.

Aged↗
PubMed1998

Does Helicobacter pylori eradication depend on the period of amoxicillin treatment? A retrospective study.

In this study, the effect of different periods of amoxicillin (AMPC) treatment on the eradication rate of Helicobacter pylori in 173 patients with peptic ulcers (gastric ulcer, 109; duodenal ulcer, 64) was investigated. AMPC (1.5 g/day) was administered for 2, 4, or 6 weeks with omeprazole (20mg/day) and plaunotol (240mg/day), a mucoprotective drug, for 8 weeks. The H. pylori eradication rate was 46.7% for 2 weeks' treatment, 83.4% for 4 weeks' treatment, and 100% for 6 weeks' treatment. The eradication rate had a good correlation with the period of AMPC treatment. The healing rates of peptic ulcer at 4 and 8 weeks were 93.3% and 100%, respectively, in the 2-week group, 98.0% and 99.3% in the 4-week group, and 85.7% and 100% in the 6-week group. The recurrence rate of gastric and duodenal ulcers was 3.5% and 0% respectively, in the patients in whom H. pylori was eradicated and 30.0% and 40%, respectively, in the patients in whom H. pylori was not eradicated for 12 months after the H. pylori eradication treatment. Adverse effects of this regimen were observed in 5 (2.9%) of the 173 patients. Diarrhea was observed in 3 patients and eruption in 2. These adverse effects disappeared within a few days after only AMPC was withdrawn. Therefore, these may be caused by AMPC. The eradication rate of H. pylori depends on the period of AMPC treatment. This regiment, AMPC (1.5g/day) + omeprazole (20mg/day) + plaunotol (240mg/day), is safe and well tolerated for eradication of H. pylori.

Adult↗
PubMed1998

Heparin-binding epidermal growth factor-like growth factor stimulates mitogenic signaling and is highly expressed in human malignant gliomas.

We previously reported that schwannoma-derived growth factor (SDGF), a member of heparin-binding epidermal growth factor (EGF) family, participates in autocrine pathways and promotes rat glioma cell growth. To investigate the potential role of similar molecules in human gliomas, we examined 7 human glioma cell lines and 11 glioblastoma specimens for expression of the human homologue of SDGF, amphiregulin (AR), as well as heparin-binding EGF-like growth factor (HB-EGF). Northern blot analysis revealed that only one cell line and no tumor specimens expressed AR mRNA. In contrast, HB-EGF mRNA was expressed in all human glioma cell lines and its level of expression was two- to five-fold higher than that of control brain tissues in 8 of 11 glioblastoma cases. Immunohistochemistry demonstrated that membrane-anchored HB-EGF (proHB-EGF) and EGFR were co-expressed in 44% of 34 human malignant gliomas. Introduction of exogenous HB-EGF (10 ng/ml) increased human glioma cell proliferation, and anti-HB-EGF blocking antibodies reduced the growth of glioma cells by 30-40%, confirming the presence of an autocrine loop. When added to the medium, transforming growth factor-alpha, basic fibroblast growth factor, or HB-EGF rapidly induced HB-EGF mRNA expression. These results indicate that HB-EGF and proHB-EGF contribute to the growth of human malignant glioma cells, most likely through autocrine and juxtacrine mechanisms.

Amphiregulin↗
PubMed1998

Advance directives and other medical decisions concerning the end of life in cancer patients in Japan.

The purpose of our survey was to investigate the experience of physicians regarding advance directives and other medical decisions concerning the end of life. A postal questionnaire was sent to 500 Japanese physicians who were most involved in medical care of terminal patients. A total of 339 (68%) physicians responded. In dealing with terminal patients, approximately half gave priority to their patients' wishes for medical care, if known, regardless of the patient's competency. Of the respondents, 149 had been presented with advance directives by their patients and 35% followed all advance directives presented in their practice. Cardiopulmonary resuscitation (CPR) for arrested patients to enable their family to be at the bedside at the time of the death was common. More than 60% of the respondents thought that active euthanasia and assisted suicide were never ethically justified. Our study indicates that the wishes of patients are currently not always given top priority in medical decisions concerning the end of life.

Adult↗
PubMed1998

Telomerase activity in 144 brain tumours.

Unlimited proliferation in immortalized cells is believed to be highly dependent on the activity of telomerase, a ribonucleoprotein that synthesizes telomeric repeats onto chromosome ends. Using a polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) assay, we analysed telomerase activity in 99 benign and 45 malignant brain tumours. The TRAP assay results were quantitated by normalizing the telomerase activity of each specimen to that of human glioma cell line T98G to obtain the relative telomerase activity. Telomerase activity was also assessed visually from the autoradiograms as being positive or negative. One hundred and sixteen tumours with negative telomerase activity had null relative telomerase activity, whereas 28 tumours with positive telomerase activity had relative telomerase activities of 12-84.3% (mean 0% vs 36.1 +/- 19.3%, P < 0.0001). Thus, quantification of telomerase activity confirmed the results of the visual evaluation of telomerase activity on autoradiograms. Based on the assessment, malignant brain tumours had a higher positive rate of telomerase activity than benign tumours (57.8% vs 2.0%, P < 0.001). These data indicate that positive telomerase activity is strongly associated with malignant brain tumours and is rather rare in benign tumours, such as neurinomas or meningiomas.

Brain Neoplasms↗
PubMed1998

Postgraduate education in medical ethics in Japan.

The objective of this paper was to investigate what kind of postgraduate education in medical ethics medical residents in Japan receive and what they want for ethical education and guidelines. Sixteen teaching hospitals that provide a general internal medicine residency programme in Japan were used (145 medical residents working at the departments of general internal medicine). A total of 114 residents participated in our survey, yielding a response rate of 79%. Of these, 28% received education in medical ethics more than once a month; 24% were offered it only when ethical problems were involved in actual patient care; and 18% answered that opportunities were very rare and sporadic. A full 30% had received no education in medical ethics at all. Many residents (71%) learned medical ethics from individual supervising doctors. A majority of the residents had been taught about informed consent (79%) and doctor-patient relationships (54%); 46% had learned about the appropriateness of truth telling and of ethical decisions regarding withholding and withdrawing a life-sustaining treatment, respectively. A total of 85 residents (75%) wanted to have more comprehensive education in medical ethics, 13% could not decide, and 12% did not want it. Many (66%) thought that both doctors and ethical philosophers should jointly teach medical ethics in postgraduate residency programmes. The results suggest that many residents desire more comprehensive and interdisciplinary education in medical ethics and educators in Japan should aim to develop education programmes to meet these desires.

Attitude of Health Personnel↗
PubMed1998

Expression and growth stimulatory effect of fibroblast growth factor 9 in human brain tumors.

OBJECTIVE: Fibroblast growth factor 9 (FGF-9) is a relatively new member of the FGF family isolated from the conditioned medium of a human glioblastoma cell line as a secreting type factor that exhibits a growth-stimulating effect on primary glial cells. To elucidate the roles of FGF-9 in human brain tumors, the expression and biological activities of FGF-9 were studied using culture cells and surgically obtained tumor specimens. METHODS: Measurement of FGF-9 and basic FGF in conditioned media of cell cultures was performed by using a sandwich enzyme immunoassay. The mitogenic effect of FGF-9 was evaluated by cell growth studies. FGF-9 expression in vivo was demonstrated by immunohistochemistry. RESULTS: One of 4 glioma cell lines and 4 of 16 human meningiomas examined actually secreted detectable amounts of FGF-9 proteins. In comparison, basic FGF production was detected from 3 of 4 glioma cell lines and 11 of 16 human meningiomas. Similarly to basic FGF, recombinant human FGF-9 significantly stimulated the in vitro cell proliferation in three of four glioma cell lines investigated in a dose-dependent manner. A time course growth study using U87 MG cells revealed an accelerated growth stimulation by FGF-9 after Day 4. The growth stimulatory activity was also shown in three of four human meningiomas studied. Moderate to strong immunoreactivity for FGF-9 was observed in 40 (82%) of 49 human brain tumors examined irrespective of origin, tumor type, grade of malignancy, or whether initial or recurrent. In contrast, strong immunostaining was localized in neurons in the normal human cerebral cortex. CONCLUSION: The present findings suggest that FGF-9 may be involved in the biology of human brain tumors with a possible importance in tumor cell growth. Whether the growth factor is more generally involved in oncogenesis of human tumors awaits further investigation.

Brain↗
PubMed1998

Cost-effectiveness analysis of partner notification program for human immunodeficiency virus infection in Japan.

Successful implementation of partner notification program (PNP) as a part of human immunodeficiency virus (HIV) prevention strategies in some developed countries motivated the execution of cost-effectiveness analysis of this program in Japan. Total number of HIV infected individuals and best estimated number of their partners in 1995 were used to elicit incremental cost-effectiveness ratio over no partner notification program. Index cases and their HIV positive partners world change their sex practice to safer one, thus preventing HIV transmission at a certain rate. This was translated to prevention of certain number of new HIV carriers and finally life years gained were calculated for it. The incremental cost-effectiveness ratio was US$ 4,930 per life year gained. Sensitivity analysis indicated that partner notification program was cost-effective over a wide range of assumptions. These results compare favorably with other medical interventions in Japan. In conclusion, the results of this analysis strongly support the implementation of partner notification program as a part of HIV prevention strategies in Japan.

Adult↗
PubMed1998

Telomere length, telomerase activity and telomerase RNA expression during mouse mammary tumor progression.

To investigate the roles of telomere length (mean length of the terminal restriction fragments; TRFs), telomerase activity (TA) and telomerase RNA (mTR) expression in relation to mouse mammary tumor progression, we examined a pregnancy-dependent mouse mammary tumor line (TPDMT-4) and its four autonomous sublines (T4-OI320: non-metastatic; and T4-OI165, -OI96, and -OI145: artificial metastatic) of DDD/1 mouse origin, and an autonomous growing mammary tumor (JYG-MC) showing spontaneous lung metastasis developed in BALB/c mice infected with a Chinese feral mice (Sub-Jyg)-derived mouse mammary tumor virus (JYG-MTV). Compared with normal (pregnant) mammary tissue, the TA was elevated in the TPDMT-4 tumor and in the non-metastatic subline tumor (T4-OI320) (x10 fold, respectively), and was further increased (x13-15 fold) in parallel with the acquisition of metastatic potential (T4-OI165, -OI96, and -OI145). The mTR level was upregulated (x2.7-2.8 fold) in all autonomous growing tumors compared to the normal counter-part, but not in TPDMT-4. The TRF was shorter in accord with tumor progression (normal mammary tissue, 48 kb; TPDMT-4, 45 kb; T4-OI320, 37 kb; T4-OI165, -OI96 and -OI145, mean 37.7 kb; and JYG-MC, 21 kb). These results suggest that the activation of TA occurs as an early event at the stage of hormone-dependent tumorigenesis, followed by the up-regulation of mTR expression in accordance with the acquisition of autonomous growth, and then further activation of TA occurs when the tumor acquires metastatic potential. The TRF shortening was in parallel with the tumor progression.

Animals↗
PubMed1997

Caspase-dependent apoptosis of COS-7 cells induced by Bax overexpression: differential effects of Bcl-2 and Bcl-xL on Bax-induced caspase activation and apoptosis.

Bcl-2 family proteins and ICE/CED-3 family proteases (caspases) are regarded as the basic regulators of apoptotic cell death. They are evolutionarily conserved and implicated in a variety of apoptosis. However, the precise mechanism by which these two families interact to regulate cell death is not yet known. In this study, we found that the overexpression of the Bcl-2 family member Bax induced apoptotic cell death in COS-7 cells through the activation of CPP32 (caspase-3)-like proteases that cleaved the DEVD tetrapeptide. This apoptotic cell death was suppressed by the viral proteins CrmA and p35, as well as by the chemically synthesized caspase inhibitors Z-Asp-CH2-DCB and zVAD-fmk. We also found that the Bax-induced apoptosis of COS-7 cells was suppressed by Bcl-xL and Bcl-2, though both Bcl-xL and Bcl-2 similarly prevented etoposide-induced apoptosis in COS-7 cells. In addition, Bcl-xL inhibited the activation of caspase-3-like proteases accompanying Bax-induced COS-7 cell death but Bcl-2 did not. These results indicate that the caspase activation is essential for Bax-induced apoptosis, and that the ability of Bcl-2 and Bcl-xL to prevent the Bax-induced caspase activation and apoptosis in COS-7 cells could be differentially regulated. Our results also suggest that Bcl-2 family proteins function upstream of caspase activation and control apoptosis through the regulation of caspase activity.

Animals↗
PubMed1997

Pim-1 kinase stimulates c-Myc-mediated death signaling upstream of caspase-3 (CPP32)-like protease activation.

Pim-1 oncoprotein is a serine/threonine kinase that can closely cooperate with c-Myc in lymphomagenesis, as does Bcl-2. Although the molecular mechanism of this cooperative transformation remains unknown, it is speculated that, similar to Bcl-2, Pim-1 contributes to transformation by inhibiting apoptosis. In this study, therefore, we examined the effect of Pim-1 expression on c-Myc-mediated apoptosis of Rat-1 fibroblasts triggered by serum deprivation. Our results showed that, rather than inhibiting apoptosis, Pim-1 expression stimulated c-Myc-mediated apoptosis in Rat-1 fibroblasts. Pim-1 stimulated c-Myc-mediated apoptosis through an enhancement of the c-Myc-mediated activation of caspase-3 (CPP32)-like proteases, since the suppression of this activity by a specific caspase inhibitor abolished the apoptosis stimulation by Pim-1. A kinase-defective Pim-1 mutant failed to stimulate c-Myc-mediated apoptosis, and Pim-1 expression alone in the absence of c-Myc overexpression did not induce apoptosis of serum-deprived Rat-1 cells, indicating that the kinase activity of Pim-1 and the activated c-Myc signaling pathway were required for apoptosis stimulation by Pim-1. Together, these results suggest that Pim-1 oncoprotein stimulates as a serine/threonine kinase the death signaling elicited by c-Myc at a step upstream of caspase-3-like protease activation in Rat-1 fibroblasts. Our results also suggest that Pim-1 kinase might function cooperatively with c-Myc through the phosphorylation of a factor(s) which regulates the common signaling pathway involved in c-Myc-mediated apoptosis and transformation.

Animals↗
PubMed1997

Increased expression of midkine during the progression of human astrocytomas.

Midkine (MK), a member of a new family of neurotrophic and angiogenic growth factors whose expression is developmentally regulated, is produced in fetal astrocytes. Malignant astrocytomas, one of the most neovascularized tumors, are derived from astrocytes. There has been no investigation of the expression of MK in human astrocytic tumors. To determine if increased levels of MK expression correlate with the progression of human astrocytomas, we examined surgical specimens of astrocytic tumors of various grades using Northern and Western blotting. MK mRNA and protein expression levels were higher in high-grade astrocytomas (anaplastic astrocytomas and glioblastomas) than in low-grade astrocytomas. As shown by in situ hybridization, MK mRNA expression was intense in a majority of glioblastoma cells but was weak in a small number of low-grade astrocytoma cells. These findings suggest that MK expression correlates with the malignant progression of astrocytomas. The aberrant MK expression in high-grade astrocytomas may underlie their rapid growth and well-vascularized features.

Astrocytoma↗