Biomedical subjects

Y Onishi

Publications and source records attributed to Y Onishi.

At least 91 records · Page 5Linked to original sources

PubMed1997

Inflammation and apoptosis.

Apoptosis is a highly regulated form of programmed cell death defined by distinct morphological and biochemical features; it plays an important role in embryogenesis and the maintenance of cellular and tissue homeostasis in multicellular organisms. Its perturbation has been implicated in a wide range of patho-physiological stages, including autoimmune, bacterial, and viral disease, and degenerative disorders. The critical role of apoptosis in eliminating harmful or injured cells from tissues suggests its participation in inflammatory processes and in the resolution of inflammatory reactions. In this article, we briefly review the molecular mechanism of apoptosis and the role of apoptosis in inflammation.

Animals↗

PubMed1997

Protein synthesis dependent and independent apoptosis of murine splenic T cells.

To elucidate the mechanism of apoptosis in matured T cells, we examined the effect of phorbol esters capable of activating protein kinase C, cAMP agonists, calcium ionophores, and dexamethasone on apoptosis in mouse splenic T cells. All of these agents induced apoptosis in thymocytes. Neither phorbol esters nor calcium ionophores induced apoptosis in the splenic T cells. Dibutyrylcyclic AMP induced apoptosis in splenic T cells but to a lesser extent than that in thymocytes. The results suggest that matured T cells are more resistant to various apoptogenic stimuli than thymocytes. Dexamethasone induced apoptotic cell death in splenic T cells as well as in thymocytes. Cycloheximide, an inhibitor of protein synthesis which completely inhibited thymocyte apoptosis, induced slight apoptosis in splenic T cells, but it inhibited the dexamethasone-induced apoptosis to a level at which cycloheximide induced apoptosis, indicating that at least two pathways of apoptosis exist in peripheral T cells; one protein synthesis dependent and the other independent. Taken together, the results suggest that the apoptosis of peripheral T cells is regulated by a mechanism different from that of thymocytes.

Animals↗

PubMed1996

Molecular cloning of the genes suppressed in RVC lymphoma cells by topoisomerase inhibitors.

Etoposide is a topoisomerase II inhibitor that induces DNA cleavable complex and has been used as an antitumor drug. We isolated two genes that were transcriptionally suppressed at an early stage of incubation in etoposide-treated RVC lymphoma cells, using modified PCR-based subtractive hybridization. Sequencing revealed that one of these genes, which was approximately 1.7 kb and which encoded a protein of 320 amino acids, was identical to hnRNP A1. The other was a novel gene of about 2.2 kb encoding a protein of 469 amino acids. These genes were also down-regulated in the cells incubated with camptothecin, a topoisomerase I inhibitor that induces DNA single strand breaks, but not in those exposed to ICRF-154, a topoisomerase II inhibitor that does not induce DNA cleavable complex formation. These results suggest that the early down-regulation of these genes contributes to the cytotoxicity of the topoisomerase inhibitors that induce DNA cleavage.

Amino Acid Sequence↗

PubMed1996

Vaccination of tumor cells transfected with the B7-1 (CD80) gene induces the anti-metastatic effect and tumor immunity in mice.

The present study demonstrates that the transfection of B7-1 or its variant MB7-2 genes into MHC class I+ tumor cells (B16-BL6 or K1735-M2 melanoma) resulted in the remarkable reduction of lung metastasis caused by i.v. injection into immunocompetent syngeneic mice. However, i.v. injection of the transfectants into T cell-deficient nude mice did not affect reduction of lung tumor colonies as compared with parental wild-type tumors, suggesting that such an inhibitory effect was closely associated with T cell-mediated responses. The reduced metastasis of B7+ tumor cells consequently led to the significant prolongation of survival. Expression of B7 on tumor cells did not influence the tumorigenicity in vivo and tumor cell invasion into basement membrane Matrigel in vitro. We also found that immunization of X-irradiated B7 transfectants was effective as a tumor vaccine for preventing lung metastasis caused by i.v. injection of B7- parental B16-BL6 cells but not against other syngeneic 3LL tumors. Thus, the B7-mediated anti-metastatic effect was tumor-specific. Vaccinations of irradiated B7+ tumor cells before and after surgical excision of the s.c. inoculated primary B7- tumors on day 21 achieved effectively the prevention of spontaneous lung metastasis. Our report that vaccination of irradiated B7+ tumor cells led to a therapeutic effect in an established tumor metastasis model clearly expands and confirms previous related observations.

Animals↗

PubMed1996

Decrease in benzodiazepine receptor binding in a patient with Angelman syndrome detected by iodine-123 iomazenil and single-photon emission tomography.

A receptor mapping technique using iodine-123 iomazenil and single-photon emission tomography (SPET) was employed to examine benzodiazepine receptor binding in a patient with Angelman syndrome (AS). AS is characterized by developmental delay, seizures, inappropriate laughter and ataxic movement. In this entity there is a cytogenic deletion of the proximal long arm of chromosome 15q11-q13, where the gene encoding the GABAA receptor beta3 subunit (GABRB3) is located. Since the benzodiazepine receptor is constructed as a receptor-ionophore complex that contains the GABAA receptor, it is a suitable marker for GABA-ergic synapsis. To determine whether benzodiazepine receptor density, which indirectly indicates changes in GABAA receptor density, is altered in the brain in patients with AS, we investigated a 27-year-old woman with AS using 123I-iomazenil and SPET. Receptor density was quantitatively assessed by measuring the binding potential using a simplified method. Regional cerebral blood flow was also measured with N-isopropyl-p-[123I]iodoamphetamine. We demonstrated that benzodiazepine receptor density is severely decreased in the cerebellum, and mildly decreased in the frontal and temporal cortices and basal ganglia, a result which is considered to indicate decreased GABAA receptor density in these regions. Although the deletion of GABRB3 was not observed in the present study, we indirectly demonstrated the disturbance of inhibitory neurotransmission mediated by the GABAA receptor in the investigated patient. 123I-iomazenil with SPET was useful to map benzodiazepine receptors, which indicate GABAA receptor distribution and their density.

Adult↗

PubMed1996

Delayed image of iodine-123 iomazenil as a relative map of benzodiazepine receptor binding: the optimal scan time.

"Delayed" single-photon emission tomograpic (SPET) images after an intravenous bolus injection of iodine-123 iomazenil have been used as a relative map of benzodiazepine receptor binding. We determined the optimal scan time for obtaining such a map and assessed the errors of the map. SPET and blood data from six healthy volunteers and five patients were used. A three-compartment kinetic model was employed in simulation studies and analyses of actual data. The simulation studies suggested that, in the normal brain, the scan time at which a single SPET image best represented the relative receptor binding was 3.0-3.5 h post-injection. This finding was supported by actual data from the volunteers. The simulation studies also suggested that the optimal scan time was not greatly changed by the variability of the input functions, and that the error in the SPET image contrast in the vicinity of the optimal scan time was not increased by changes in the tracer kinetics in the entire brain. The SPET image contrast in the patients at 3.0 h post-injection agreed well with the reference receptor binding estimated by kinetic analysis, with a mean error of 3.6%. These findings support the use of a single SPET image after bolus injection of [123I]iomazenil as a relative map of benzodiazepine receptor binding. For this purpose, a SPET scan time of 3.0-3.5 h post-injection is recommended.

Alzheimer Disease↗

PubMed1996

Molecular characterization of the Drosophila Mo25 gene, which is conserved among Drosophila, mouse, and yeast.

To study the general physiological role of the Mo25 gene, which has been cloned from mouse cleavage-stage embryos, we isolated a Drosophila equivalent, dMo25, cDNA from an embryo cDNA library. The 2,222 nucleotides contained a single open reading frame encoding a polypeptide of 339 amino acid residues with a calculated molecular mass of 39,278 daltons. The deduced amino acid sequence of the dMo25 cDNA had 69.3% identity with mouse Mo25. A homology search revealed that these were similar to a protein encoded in an open reading frame near the calcineurin B subunit gene on chromosome XI in Saccharomyces cerevisiae. In particular, the carboxy-terminal region was highly conserved in Drosophila, mouse, and yeast. The dMo25 gene was mapped to the left arm of the third chromosome at 73AB, and 2.3- and 1.8-kb mRNA bands were detected during development and in adult Drosophila. Conservation of the gene structure and the wide expression profile indicated that the function of the gene is likely to be fundamental in many cell types as well as during development.

Amino Acid Sequence↗

PubMed1996

Molecular cloning of Elk-3, a new member of the Ets family expressed during mouse embryogenesis and analysis of its transcriptional repression activity.

We isolated a cDNA clone, Elk-3, that encodes a novel Ets transcription factor from 16-day mouse embryos. The deduced amino acid sequence of the protein was homologous to human ELK-1 and SAP-1. This protein, ELK-1, and SAP-1 shared some unique structural properties such as an Ets DNA-binding site in the amino-terminal region, a serum response factor interacting domain and phosphorylation sites of serine or threonine residues in the carboxy-terminal region. Northern blotting weakly revealed that two transcripts of 4 and 2.1 kb are expressed in the adult ovary and lung and a 2.1-kb transcript predominated in 8- to 14-day embryos. We assayed the transcriptional activities of Elk-3 protein on the cytokeratin EndoA enhancer containing Ets binding sites in endodermal cells. Elk-3 protein strongly repressed enhancer activity but did not affect the activity of the basal promoter in the absence of the enhancer. Furthermore, Elk-3 can suppress the activity of Ets-2 as the transcriptional activator on the EndoA enhancer. These data suggested that the Elk-3 gene product plays a role in transcriptional regulation during embryogenesis.

Amino Acid Sequence↗

PubMed1996

Noninvasive quantification of iodine-123-iomazenil SPECT.

UNLABELLED: The feasibility of a noninvasive method for quantification of [123I]iomazenil binding using a standardized arterial input function and a single venous blood sample was assessed in normal volunteers. METHODS: Serial SPECT images and blood data from six healthy male volunteers after intravenous injection of [123I]iomazenil were used. The standardized input function was derived by averaging the six subjects' arterial curves. Individual input functions were estimated by calibrating the standardized input function with one-point venous blood radioactivity concentration. Ligand transport (K1) and receptor binding were computed from the estimated input functions and two separate SPECT scans using a table look-up procedure based on a three-compartment, two-parameter model. Reference values for K1 and receptor binding were determined from the serial SPECT data and individual arterial curves using a three-compartment, three-parameter model and curve fitting. RESULTS: Analyses of the error caused by the calibration in relation to the time postinjection revealed that the optimal calibration time was 30 min postinjection. Receptor binding obtained by this simplified method correlated well with the reference values (r = 0.941) and was estimated within an error of 10% in the cerebral cortical regions. Although the estimated K1 showed relatively poor correlation (r = 0.699) with the reference value, it was an excellent relative measure in each subject. CONCLUSION: Our method provided an absolute measure of the benzodiazepine receptor binding and a relative measure of ligand transport from two SPECT scans and a venous blood sample. This method would be useful for quantitative assessment of benzodiazepine receptors in clinical settings.

Adult↗

PubMed1996

Ectopic extramammary Paget's disease affecting the upper abdomen.

We present 57-year-old man in whom ectopic extrammary Paget's disease (EMPD) affected the upper abdomen. Although the clinical appearance was suggestive of Bowen's disease or superficial basal cell epithelioma (BCE), the biopsy specimen showed EMPD histologically. Only 12 cases of ectopic EMPD have been reported (including this case). In our 20 year experience of 129 EMPD, this is the first ectopic case. Thus, the frequency of ectopic EMPD is 0.78% (one of 129) in our study. The male/female ratio in the reported 12 cases is 2: 1, nearly the same as EMPD in general (2.1: 1, in our 129 cases). The mean age of the 12 patients is 65.8 years, which is not significantly different from ordinary EMPD (66.4 years, in our 129 cases). Comparing ectopic EMPD to ordinary EMPD, clinically and histologically, we could find no difference. As they appear to be the same disease, ectopic and ordinary EMPD may share similar origins and mechanisms of occurrence. We support the hypothesis that Paget's cells originate from the remaining pluripotential germinative cells which are able to differentiate into many kinds of secreting glands.

Abdomen↗

PubMed1996

[Parametric images of central-type benzodiazepine receptor binding and ligand transport by two SPECT scans of 123I-iomazenil: relative quantification without blood data].

Parametric images of intrasubject distribution of the central-type benzodiazepine receptor binding and ligand transport were determined from two SPECT images after an intravenous bolus injection of 123I-iomazenil in six healthy volunteers and five patients by using a table look-up procedure based on a 3-compartment, 2-parameter kinetic model. Individual arterial input functions were estimated by calibrating a standardized input function with the injected dose to avoid blood sampling. The parametric images without blood data provided the same information as those determined by using measured arterial input function. A simulation study suggested that this method gave relatively small error as long as true receptor binding and ligand transport did not differ from each other in a large extent. The present method may be practical in clinical settings.

Biological Transport↗

PubMed1996

[Aortic dissection after weaning from extracorporeal circulation].

Acute aortic dissection is a rare complication of cardiac surgery. But once it happens, its outcome is often miserable. We experienced this complication after discontinuing cardiopulmonary bypass (CPB). A 56-year old man with mitral regurgitation was referred for mitral valve replacement under CPB. After weaning from extracorporeal circulation (ECC), the right radial artery pressure decreased suddenly and its waveform became flat. After 5 minutes, dissection of the ascending aorta was diagnosed by transesophageal echocardiography (TEE). We started to prevent ischemic brain damage immediately, but a severe brain damage occurred. Its early diagnosis is necessary and the prevention of critical brain damage due to low perfusion of the blood is important for anesthetic management.

Aortic Dissection↗

PubMed1995

Effects of protein tyrosine kinase inhibitors with different modes of action on topoisomerase activity and death of IL-2-dependent CTLL-2 cells.

We studied the effects of protein tyrosine kinase inhibitors with different modes of action on topoisomerase activity and cell death in CTLL-2 cells, whose growth is IL-2-dependent. The Flavonoids genistein, biochanin A, and apigenin inhibited topoisomerase II to the same extent as etoposide, a specific inhibitor of the enzyme. Methyl 2,5-dihydroxycinnamate (2,5-MeC) also inhibited topoisomerase II, but was less potent than genistein. Herbimycin A and staurosporine did not inhibit topoisomerase II. None of the inhibitors of protein tyrosine kinases examined inhibited topoisomerase I activity. All the inhibitors induced cell death with internucleosomal DNA fragmentation in the presence of IL-2. Genistein, biochanin A, and apigenin induced DNA fragmentation and cell death early in the incubation period and did not alter the profiles of phosphotyrosine proteins in either the lysate or pelleted fractions, indicating that the early cell death was induced by the inhibition of topoisomerase II activity rather than by the inhibition of protein tyrosine kinase activity. 2,5-MeC similarly induced early cell death and DNA fragmentation, but to a lesser extent than genistein presumably due to the inhibition of topoisomerase II activity. Herbimycin A induced a slow increase in DNA fragmentation and cell death, accompanied by a decrease in phosphotyrosine proteins in the pelleted fraction, suggesting that the inhibition of protein tyrosine phosphorylation, presumably of the nuclear proteins, is related to cell death and DNA fragmentation. Staurosporine-induced DNA fragmentation appeared to be due to mechanism(s) other than the inhibition of topoisomerases and protein tyrosine kinases, since it neither altered the profiles of phosphotyrosine proteins nor inhibited topoisomerase activity.

Animals↗

PubMed1995

[A case of pure alexia whose writing ability with eyes closed was superior to that with eyes open].

We compared the writing ability between eyes open (looking at one's writing) and eyes closed (without looking) in a case of pure alexia. The patient is a 84-year-old right handed man who developed pure alexia following an infarction in the distribution of the left posterior cerebral artery. He showed right homonymous hemianopsia, slight memory disorder and slight anomia. He could not read any kinds of letters and words at all though he could categorize letters: Kana (phonograms), Kanji (morphograms) and Arabic numbers, and he could distinguish the real letters from false ones. He could achieve almost 60-70% of Kana and Kanji dictation, though it was not perfect. He was often confused and could not continue writing correct letters once interrupted. He wrote poorly when looking at what he was writing. So we compared the ability of dictation with his eyes closed, and that with his eyes open. We found the former way never caused confusion and got better results, which was statistically significant (Fisher's exact test (p < 0.05)). It seemed that his visual feedback of his own writing rather caused trouble in his writing. Thus we concluded that input (reading) process and output (writing) process work simultaneously and bi-directionally. Slight impairment of writing in pure alexia patients might be caused by the effect of impairment of input (reading) process, which is simultaneously connected with the output (writing) process.

Aged↗

PubMed1995

Biphasic effect of staurosporine on thymocyte apoptosis.

When mouse thymocytes were incubated with staurosporine at low doses (1-100 nM), apoptosis was induced dose- and time-dependently. Staurosporine-induced apoptosis was dependent on macromolecular synthesis, and it was also dependent on protein phosphorylation sensitive to 1-(5-isoquinolinesulfonyl-2-methylpiperazine dihydrochloride (H-7). Whereas, staurosporine at high doses (above 500 nM) did not induce significant DNA fragmentation, rather it inhibited the DNA fragmentation induced by 12-O-tetradecanoyl-13-acetate, A23187, and dibutyrylcyclic AMP, as H-7 did. K252a, a derivative of staurosporine, induced apoptosis, which was inhibited by H-7, even at high doses. These results indicate that staurosporine had a biphasic effect on thymocyte apoptosis, a stimulatory effect at low concentration, and an inhibitory effect at high concentration. K252a had only the former action.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1995

[A case of traumatic diaphragmatic hernia accompanied with rupture of pericardium].

We experienced a case of left traumatic diaphragamatic hernia accompanied with rupture of pericardium after blunt trauma by traffic accident. A 55-year-old man who had suffered blunt chest and upper abdominal trauma because of smash of two cars when he had been turning to right in the corner was admitted to our hospital. On arrival at the hospital, the patient complained severe dyspnea that reduced by lying on his right. Another position couldn't be taken because of deterioration of dyspnea. Chest X-ray showed disappeared left diaphragmatic line and abnormal transparent mass that suggest alimentary canal in the left intrapleural space. Cardiac ultrasonography showed abnormal tubular mass close to the left side of mediastinum that deviated to right. The patient was diagnosed as traumatic diaphragmatic hernia and emergency operation was performed. Left diaphragma was lacerated sagitally toward its top for about 12 cm in length. Left pleuropericardium was seen to be lacerated longitudinally for about 8 cm in length in front of the phrenic nerve intraoperatively. Both lacerations were closed by direct suture. The patient discharged on the 37th postoperative day without phrenic nerve palsy. At making diagnosis of patient with chest and abdominal trauma, injure of diaphragma and/or pericardium also must be considered. If it is possible, operation must be performed without hesitation in order to get good prognosis.

Accidents, Traffic↗

PubMed1995

[Severe hyperbilirubinemia after cisplatin-based chemotherapy].

Cisplatin is the most effective and widely used anti-cancer drug for ovarian cancer. We report 2 cases with severe hyperbilirubinemia after cisplatin-based chemotherapy. Case 1 was a 67-year-old woman with stage IV ovarian cancer. After operation, she had 2 courses of chemotherapy consisting of cisplatin (90 mg) and cyclophosphamide (550 mg). The regimen was changed to low-dose consecutive cisplatin (10 mg/day, day 1-day 5) because of her ileus and poor performance status. After 2 courses of cisplatin alone, her total bilirubin was elevated to 19.1 mg/dl. She died of respiratory distress. At autopsy, chronic cholangiolitis with intrahepatic bile stasis were noted. Case 2 was a 60-year-old woman with stage IIIc ovarian cancer. After operation she was treated with carboplatin (383 mg/day, day 1) and cisplatin (102 mg/day, day 3). One month after completing the first chemotherapy, her bilirubin elevated to 20.5 mg/dl. It took 3 months to normalize the serum bilirubin with steroid administration. During the second course using the same regimen as in the first course, the bilirubin elevated again. Cisplatin was suspected to be the drug inducing her hyperbilirubinemia. She was consecutively treated with carboplatin alone and the bilirubin did not elevate. Both cases had blood transfusion and intravenous hyperalimentation. It is difficult to disregard the effect of other drugs and therapy. In case 2, her bilirubin elevated repeatedly after cisplatin administration. Cisplatin may thus be the drug which induces the liver dysfunction.

Aged↗

PubMed1995

[Consensus and new development in epithelial ovarian cancer chemotherapy in 1995].

Recent clinical trials have confirmed that cisplatinum combination has advantages for advanced ovarian cancer interns of response rate, response duration and disease-free time, but little advantage for overall survival. Although addition of doxorubicin to cisplatin-based chemotherapy is a matter of controversy between European countries and the USA, high-dose epirubicin, which is an analog of doxorubicin, has a potent response in relapsed cases after CDDP combination chemotherapy. Clinical trails of epirubicin + CPA + CDDP for advanced ovarian cancer and underway in Japan. Under standard supportive care, escalated CDDP dose may prolong median survival time, but its advantage for long-time survival is questionable. Trials of high-dose chemotherapy as front line treatment for advanced ovarian cancer supported by PBSCT/G-CSF in combination with assessment of scheduled AUC have been collected from many world-wide institutes. GOG demonstrated that intraperitoneal administration of CDDP with intravenous CPA had obvious superiority to intravenous CDDP and CPA in overall survival and adverse effect for stage III ovarian cancer, under the conditions that 70% of cases had minimum residual tumor (< 0.5 cm). We have to make sure whether this modality has the same effect on early and stage IV ovarian cancer. Taxol plus CDDP has promising benefits for median disease free survival and median survival time, so it is becoming the standard regimen for advanced ovarian cancer in USA. The delay of the clinical introduction of taxanes should be eliminated promptly in Japan.

Antineoplastic Combined Chemotherapy Protocols↗