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Biomedical subjects

Y Ono

Publications and source records attributed to Y Ono.

At least 361 records · Page 20Linked to original sources

[Clinical study on poor-risk patients with non-seminomatous germ cell tumor].

Between 1988 and 1996, we treated 11 poor-risk patients with non-seminomatous germ cell tumors (NSGCT) at Nagoya University Hospital. "Poor-risk" was defined as i) advanced disease equal to or greater than class 7 of the Indiana University Classification (7 patients), ii) primary mediastinal extragonadal NSGCT (2), iii) tumor markers not normalized by the induction chemotherapy (1) or iv) primary retroperitoneal NSGCT with multiple lung metastases (1). Two patients with mediastinal tumors died during the chemotherapy. The minimal volume of fluid must be administered to patients with giant mediastinal tumors. The tumor marker normalized during the induction chemotherapy in only three patients. Three patients, whose tumor markers elevated during or one month after the induction chemotherapy, eventually died of cancer. The tumor markers in five of the seven patients which had not normalized during the induction chemotherapy, had decreased to the normal range during the salvage chemotherapy and two of the five subsequently achieved the status of "no evidence of disease" (NED). Six patients with and two without normalized tumor markers underwent retroperitoneal lymph nodes dissection and/or resection of residual tumors. Pathological examination of the resected tumors showed necrosis/fibrosis in five patients and two had elevated tumor markers immediately after the surgery and eventually died of the disease. Overall, eight (73%) of 11 poor-risk patients achieved a complete response but only five (45%) eventually achieved a NED status that was maintained (6.6 +/- 3.0 years). Our results were not satisfactory, and we believe that new strategies, such as early high-dose chemotherapy, are required for poor-risk patients, who are not likely to respond well to the induction chemotherapy.

Adolescent↗

[Hemophagocytic syndrome due to miliary tuberculosis in the course of aplastic anemia].

We report a 63 year-old female with aplastic anemia (AA) who was complicated with hemophagocytic syndrome induced by systemic miliary tuberculosis. Two years before admission to our hospital, she was diagnosed as AA and had been treated with granulocyte colony-stimulating factor, erythropoietin and methenolone acetate. In May, 1996, She was transferred to our hospital because of high fever and exacervation of pancytopenia. She showed severe pancytopenia, and an increase in macrophages showing remarkable erythrophagocytosis and decrease in hemopoietic cells in the bone marrow. In initial examination, high titer of IgM antibody to herpes simplex virus type I was identified and methylprednisolone pulse therapy was started under the diagnosis of virus associated hemophagocytic syndrome. Ten days later, however, she died for intestinal hemorrhage followed by multiorgan failure. In autopsy, multiple epitheloid cell granulomas with acid-fast bacilli were found in bone marrow, lungs, liver, spleen and kidneys.

Anemia, Aplastic↗

[The treatment and prognosis of acute late rejection after kidney transplantation].

To examine the acute late rejection episodes (ALR) occurring 4 months after kidney transplantation, 330 cadaver kidney transplant recipients who were operated on between 1982 and 1996 and immunosuppressed by cyclosporine or tacrolimus were analyzed. In 213 recipients who were followed up for 5 years or longer, the frequency of ALR without an acute early rejection (AER) was 14% and ALR with AER was 16%, respectively. ALR was the strongest deteriorating factor for graft survival at the chronic stage. Judging from the renal function 1 month after an ALR episode, the complete and partial response rates were 22% and 62% with steroid treatment and 16% and 58% with DSG treatment, respectively. The 5-year graft survival after the treatment was 20% with steroid treatment and 45% with DSG treatment. Although the intensity of the rejection classified based on the Banff grading system was the strongest factor affecting the graft survival, the multivariate analysis by Cox proportional hazard model for non-pathological factors revealed that urine protein and hypertension 1 month before the episodes may also be important prognostic factors. The body weight of recipient (> 55 kg) and donor age (> 55 y.o) were slightly correlated to the graft prognosis. Due to incomplete immuno-suppressive methods for acute late rejection, the conservative nephron sparing policy after a rejection episode is inevitable to obtain better graft survival at the chronic stage.

Acute Disease↗

[Long-term results and quality of life of hemi-Kock orthotopic ileal neobladder after radical cystectomy].

We analyzed the long-term results and the quality of life in patients who received orthotopic lower urinary tract reconstruction using the Kock ileal neobladder. Between July 1990 and October 1993, 37 consecutive patients including 2 females received orthotopic hemi-Kock neobladder after radical cystectomy. In these patients, we analyzed the urinary continence, complications and urethral recurrence, and performed a questionnaire survey by mail. Good continence all day had been achieved in 71% of the patients 4 years after surgery. The rate of the pouch-related complications requiring reoperation was 27%. There was no urethral recurrence. Compared with preoperative conditions, 42% were not satisfied with urination. In these dissatisfied patients, the need to use pads in the daytime, sensation of residual urine and weak urine stream were significantly more frequent than in satisfied patients. In summary, the rate of complications was higher than that of other methods. However, the Kock orthotopic ileal neobladder is a stable procedure providing good function over the long-term.

Adult↗

[Extradural temporopolar approach for giant pituitary adenomas invading the cavernous sinus and parasellar regions].

OBJECTIVE: An extradural temporopolar approach has recently been used in the treatment of the parasellar, infrachiasmatic, or intracavernous regions. In this approach, the temporal (superficial) dural layer is separated from the deep layer (inner cavernous membrane) to expose the cavernous sinus extradurally. We report our experiences with 5 cases in which a giant pituitary adenoma invading the cavernous sinus and parasellar regions was resected via the extradural temporopolar approach. PATIENTS AND METHODS: Between January 1995 and December 1997, 60 patients with pituitary adenomas were operated on at Okayama University Hospital. The extradural temporopolar approach was used for 5 patients who had a giant pituitary adenoma invading the cavernous sinus and parasellar regions. The 5 patients were women aged from 32 to 62 years and presented with a visual dysfunction. Four patients had hormonally non-functioning pituitary adenomas and one had a growth-hormone secreting pituitary adenoma. RESULTS: The operations resulted in 1 total, 3 subtotal and 1 partial removal. There was no operative mortality or major morbidity. Transient oculomotor palsy occurred in 2 cases postoperatively. This approach provided excellent exposure of the tumor, relevant cranial nerves and arteries in and around the cavernous sinus through extradural retraction of the temporal lobe, allowing for sufficient resection of the intracavernous and parasellar portion of the tumor. Tumors invading the inferior portion of the clivus or the contralateral cavernous sinus could not be removed through this approach. CONCLUSION: Our findings suggest that the extradural temporopolar approach is useful for resection of giant pituitary adenomas invading the cavernous sinus and parasellar regions.

Adenoma↗

[Gene transduction for experimental brain tumors using recombinant adenovirus vector].

Recent advances in molecular biology have permitted significant progress toward the treatment of malignant brain tumors using gene transduction methods. Adenovirus vectors have recently been shown to transduce genes successfully into brain tumor cells both in vitro and in vivo. We have investigated the feasibility of gene transduction for brain tumors using adenovirus vectors. To evaluate in vitro transduction rate by adenovirus vectors, rat 9L gliosarcoma cells or human glioblastoma cells were infected with recombinant replication-deficient adenovirus vectors containing the E. coli beta-galactosidase gene (Adex-CALacZ) and stained with X-Gal. We observed a multiplicity of infection (MOI)-dependent rate. Approximately 100% transgene expression was achieved at a MOI of 5 after seven days of incubation. To evaluate transgene expression in a rat brain tumor model, AdexCALacZ was stereotactically injected into established rat 9L brain tumors. Intratumoral injection of AdexCALacZ resulted in high transgene expression in tumor cells. Although injection of AdexCALacZ in the normal basal ganglia resulted in broad and diffuse transduction into endogenous neural cells, direct intratumoral injection resulted in transduction that was relatively restricted to the tumor cells as well as some neighboring normal cells. Transduction rates were relatively elevated at the margin of the tumor. Our results suggest that adenovirus vectors might be a feasible method to transfer therapeutic genes into malignant brain tumors.

Adenoviridae↗

[Primary malignant lymphoma in the central nervous system treated with high dose methotrexate (MTX)-CHOP (M-CHOP)].

From December 1995 to July 1997, six patients with primary malignant lymphoma in the central nervous system were treated with 2 to 5 cycles of the M-CHOP regimen (methotrexate 3 g/m2 on day 1, cyclophosphamide 750 mg/m2 on day 1, doxorubicin 40 mg/m2 on day 1, vincristine 1.4 mg/m2 on day 1, and predonisolone 60 mg on day 1 to 14: folic acid was given 3 hours after methotrexate at 10 mg/m2 every 3 hours for 9 doses intravenously). Five patients achieved complete remission (CR) and one experienced partial remission (PR). Posttherapeutic studies were performed in all patients with an average follow-up period of 20.1 months (range 8.1-26.8 months) after confirming the diagnosis. There was no evidence of recurrence of the tumors or growth of residual tumors in any of the patients in this period. The major toxic effect was myelosupression with leukopenia. Alopecia was observed in all patients. No treatment-related deaths were observed. The M-CHOP regimen seems to be a promising treatment for primary malignant lymphoma in the central nervous system.

Adult↗

Consensus statement on social anxiety disorder from the International Consensus Group on Depression and Anxiety.

OBJECTIVE: The goal of this consensus statement is to provide primary care clinicians with a better understanding of management issues in social anxiety disorder (social phobia) and guide clinical practice with recommendations for appropriate pharmacotherapy. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Other faculty invited by the chair were Julio Bobes, Deborah C. Beidel, Yukata Ono, and Herman G. M. Westenberg. EVIDENCE: The consensus statement is based on the 7 review papers published in this supplement and on the scientific literature relevant to the issues reviewed in these papers. CONSENSUS PROCESS: The group met over a 2-day period. On day 1, the group discussed each review paper, and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. CONCLUSIONS: The consensus statement underlines the importance of recognizing social anxiety disorder and provides recommendations on how it may be distinguished from other anxiety disorders. It proposes definitions for response and remission and considers appropriate management strategies. Selective serotonin reuptake inhibitors are recommended as first-line therapy, and effective treatment should be continued for at least 12 months. Long-term treatment is indicated if symptoms are unresolved, the patient has a comorbid condition or a history of relapse, or there was an early onset of the disorder.

Anxiety Disorders↗

Sympathetic reinnervation demonstrated on serial iodine-123-metaiodobenzylguanidine SPECT images after cardiac transplantation.

The transplanted heart is without autonomic nervous control in the early postsurgical period. We present here a case of cardiac transplantation in which 123I-metaiodobenzylguanidine (MIBG) SPECT and an exercise-loading test were used to monitor the sympathetic reinnervation. The distribution of myocardial 123I-MIBG uptake extended with time from 1 to 2 yr after surgery. However, functional improvement, estimated by the heart rate response to exercise, was not discernable during this period. The findings in this case suggest the feasibility of 123I-MIBG SPECT imaging in the serial monitoring of sympathetic reinnervation after transplantation and that scintigraphic evidence of reinnervation precedes functional recovery.

3-Iodobenzylguanidine↗

Direct visualization of the translocation of the gamma-subspecies of protein kinase C in living cells using fusion proteins with green fluorescent protein.

We expressed the gamma-subspecies of protein kinase C (gamma-PKC) fused with green fluorescent protein (GFP) in various cell lines and observed the movement of this fusion protein in living cells under a confocal laser scanning fluorescent microscope. gamma-PKC-GFP fusion protein had enzymological properties very similar to that of native gamma-PKC. The fluorescence of gamma-PKC- GFP was observed throughout the cytoplasm in transiently transfected COS-7 cells. Stimulation by an active phorbol ester (12-O-tetradecanoylphorbol 13-acetate [TPA]) but not by an inactive phorbol ester (4alpha-phorbol 12, 13-didecanoate) induced a significant translocation of gamma-PKC-GFP from cytoplasm to the plasma membrane. A23187, a Ca2+ ionophore, induced a more rapid translocation of gamma-PKC-GFP than TPA. The A23187-induced translocation was abolished by elimination of extracellular and intracellular Ca2+. TPA- induced translocation of gamma-PKC-GFP was unidirected, while Ca2+ ionophore-induced translocation was reversible; that is, gamma-PKC-GFP translocated to the membrane returned to the cytosol and finally accumulated as patchy dots on the plasma membrane. To investigate the significance of C1 and C2 domains of gamma-PKC in translocation, we expressed mutant gamma-PKC-GFP fusion protein in which the two cysteine rich regions in the C1 region were disrupted (designated as BS 238) or the C2 region was deleted (BS 239). BS 238 mutant was translocated by Ca2+ ionophore but not by TPA. In contrast, BS 239 mutant was translocated by TPA but not by Ca2+ ionophore. To examine the translocation of gamma-PKC-GFP under physiological conditions, we expressed it in NG-108 cells, N-methyl-D-aspartate (NMDA) receptor-transfected COS-7 cells, or CHO cells expressing metabotropic glutamate receptor 1 (CHO/mGluR1 cells). In NG-108 cells , K+ depolarization induced rapid translocation of gamma-PKC-GFP. In NMDA receptor-transfected COS-7 cells, application of NMDA plus glycine also translocated gamma-PKC-GFP. Furthermore, rapid translocation and sequential retranslocation of gamma-PKC-GFP were observed in CHO/ mGluR1 cells on stimulation with the receptor. Neither cytochalasin D nor colchicine affected the translocation of gamma-PKC-GFP, indicating that translocation of gamma-PKC was independent of actin and microtubule. gamma-PKC-GFP fusion protein is a useful tool for investigating the molecular mechanism of gamma-PKC translocation and the role of gamma-PKC in the central nervous system.

3T3 Cells↗

Regression of experimental brain tumors with 6-thioxanthine and Escherichia coli gpt gene therapy.

The identification of transgenes with antitumor activity is critical to the development of gene therapy of cancer. Retrovirus-mediated transfer of the Escherichia coli gpt gene into rat C6 glioma cells without subsequent selection still inhibited the proliferation of this mixed polyclonal population upon addition of the prodrug, 6-thioxanthine, with an ID50 of 4.1 microM, whereas parental C6 cells were not affected at a concentration of 500 microM. In a time-course assay, effects of the prodrug on the mixed polyclonal cell proliferation required at least 10 days of exposure. In mixed co-cultures, a bystander effect was not present over the first 4 days of prodrug exposure, but required trypsinization of the co-cultures and replating at lower densities. This "modified" bystander assay thus revealed a 50% decrease in C6 cell proliferation, even when the initial ratio of gpt-expressing to parental C6 cells was as low as 1:19. In a nude mouse model of subcutaneous tumors, co-grafts of C6 glioma and gpt-retrovirus producer cells displayed retarded growth upon exposure to 6-thioxanthine (6-TX). In a nude mouse model of intracerebral tumors, grafting of the gpt-retrovirus producer cells leads to an 80% reduction in intracerebral tumor volumes after 6-TX treatment. This reduction results in a 28% increase in the mean time of survival of animals that harbor intracerebral tumors (p < 0.0005). These antitumor effects indicate that the gpt/6-TX enzyme/prodrug pair is a promising alternative to the thymidine kinase gene and ganciclovir combination in the gene therapy of cancer.

Animals↗

The role of the cytoskeleton in migration and proliferation of a cultured human gastric cancer cell line using a new metastasis model.

Using an in vitro model for investigating the mechanism of migration and proliferation of a cultured human gastric cancer cell line which we established recently, we studied the suppressive effect of inhibitors of the cytoskeleton proteins, actin and myosin, on the migration and proliferation of cancer cells. These inhibitors suppressed the capacity of cancer cells to migrate and proliferate dose-dependently. Thus the integrity of the cytoskeletal system may play an important role in the mechanism of metastasis of gastric cancer cells.

Actins↗

Activation of protein kinase C by tyrosine phosphorylation in response to H2O2.

Protein kinase C (PKC) isoforms, alpha, betaI, and gamma of cPKC subgroup, delta and epsilon of nPKC subgroup, and zeta of aPKC subgroup, were tyrosine phosphorylated in COS-7 cells in response to H2O2. These isoforms isolated from the H2O2-treated cells showed enhanced enzyme activity to various extents. The enzymes, PKC alpha and delta, recovered from the cells were independent of lipid cofactors for their catalytic activity. Analysis of mutated molecules of PKC delta showed that tyrosine residues, which are conserved in the catalytic domain of the PKC family, are critical for PKC activation induced by H2O2. These results suggest that PKC isoforms can be activated through tyrosine phosphorylation in a manner unrelated to receptor-coupled hydrolysis of inositol phospholipids.

Amino Acid Sequence↗