Publications by authors named "Oku N"

Unlabelled: At least two quantitative rCBF measurements are needed to evaluate rCBF changes with pharmacological intervention. We have developed the split dose 123I-IMP SPECT method, which enables measurement of rCBF to be repeated in a short time.

Methods: Thirty-one cerebrovascular disease patients were investigated to assess reproducibility and vasoreactivity to acetazolamide.

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A 76-year-old woman with painful erythema on legs and right oculomotor disturbance was diagnosed as neoplastic angioendotheliosis (NAE, B cell type) by skin biopsy. Remission was obtained by 2 courses of VEPA regimen. But 3 months later, she relapsed with right oculomotor, optic, trochlear and trigeminal nerve disturbance which suggested that she had Tolosa-Hunt syndrome.

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Organ-specific colonization of metastatic tumor cells is regulated through complex interactions of specific adhesion molecules on the tumor cell surface with organ specific microvascular endothelium. The present paper shows the real time tumor cell trafficking under the actual blood flow, which became able to be determined using a new technology, positron emission tomography. This technology would be useful to evaluate the interaction of characteristic tumor cells with various organs in vivo.

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Since transient swelling during phase transition of liposomes with hyper-osmotic internal aqueous phase may cause permeation of large molecules through the lipid bilayer, this type of liposomes can be useful for delivering macromolecules. In fact, thermosensitive liposomes containing an internal solution with osmotic pressure 2-fold higher than the physiologic level and sized through 200-nm pore, released encapsulated macromolecules such as dextran (M(r) 144,000) effectively when they were incubated at 40-42 degrees C. These liposomes were stable in the presence of serum compared to the liposomes with internal osmotic pressure more than 3-fold higher than the physiologic level.

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Using two-color flow cytometry, we analyzed the subpopulations of CD34+ stem and progenitor cells in the blood and bone marrow from 10 patients with hematological malignancies. Peripheral blood mononuclear cells (PBMNC) harvested after chemotherapy (high-dose Ara C and VP-16) and rhG-CSF, and BM mononuclear cells, which were obtained before chemotherapy (BMMNCbefore) and after the stem cell collection (BMMNCafter) were isolated by Ficoll-Hypaque centrifugation. The purified cells were stained with FITC-conjugated anti-CD34 antibody and one of the following PE-conjugated antibodies: anti-CD7, CD10, CD11b, CD11c, CD13, CD19, CD33, CD38, CD45RO, CD56, and HLA-DR.

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The reconstitution of lymphocyte subsets after high-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT) was studied using two-color flow cytometry in 14 patients with acute leukemia (four AML and two ALL) and malignant lymphoma (six NHL and two HD). The CD3+HLA-DR+ lymphocytes (activated T cells) and CD8+ lymphocytes increased markedly by 4 weeks after PBSCT. Most of the increased CD8+ lymphocytes were CD11b-, S6F1+ cells and CD8+CD11b+ cells remained low throughout the follow-up period.

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A 69-year-old woman with IgE/kappa plasma cell leukemia (PCL) was treated with a sequential combination of VAD (vincristine, doxorubicin, dexamethasone) and MP (melphalan, prednisolone) followed by interferon-alpha (IFN alpha). A complete remission was achieved for 14 months. Maintenance therapy with IFN alpha has continued for an additional 10 months.

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A 67-year-old male was admitted to our hospital because of anemia, thrombocytopenia, and renal failure. On admission he showed splenomegaly and elevated serum LDH level. Bone marrow showed hypercellularity with massive infiltration of lymphoblastoid cells.

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To examine the effect of granulocyte colony-stimulating factor (G-CSF) on hematopoietic recovery after high-dose chemotherapy and peripheral blood progenitor cell transplantation (PBPCT), 20 patients with hematologic malignancies were divided into two groups. One group was given G-CSF at a daily dose of 50 micrograms/m2 subcutaneously, the other received no G-CSF. Neutrophil recovery was accelerated in the G-CSF treated patients and exceeded 0.

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Unlabelled: In the management of major cerebral artery obstruction, cerebral perfusion reserve is key to introducing cerebral revascularization surgery. The purpose of this study was to evaluate the feasibility of assessing cerebral perfusion reserve by consecutive 99mTc-hexamethyl-propyleneamine oxime (99mTc-HMPAO) SPECT with 5% carbon dioxide (CO2) inhalation.

Methods: The CO2 inhalation and consecutive 99mTc-HMPAO SPECT study was performed on 30 chronic ischemic cerebrovascular disease patients with unilateral major cerebral artery obstruction and on 27 patients without.

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The effect of hepatocyte growth factor/scatter factor (HGF/SF) and epidermal growth factor (EGF) on cadherin-mediated adhesion of human carcinoma cells was studied. HGF/SF induced scattering of colonic adenocarcinoma HT29 and gastric adenocarcinomas MKN7 and MKN74 cells. Likewise, EGF induced scattering of HT29 and MKN7 cells.

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Long-circulating liposomes.

Crit Rev Ther Drug Carrier Syst

October 1995

Liposomes have been investigated for use as drug carriers, and many previous studies have demonstrated enhanced efficacy of encapsulated drugs and the reduction of the side effects of drugs so entrapped. In many cases liposomal drugs are administered via the bloodstream. The stability in the bloodstream, clearance, and biodistribution are dependent on the composition, size, and charge of the liposomes.

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Hepatocyte growth factor (HGF), a protein with pleiotropic biological activity affecting cell growth and motility, was found to markedly activate prostaglandin production in human gastric carcinoma TMK-1 cells. HPLC analysis revealed that HGF stimulated the production of prostaglandin E2 (PGE2), which is the major prostaglandin produced in these cells. HGF maximally stimulated PGE2 production at a concentration of 10 ng/ml, and it was a more potent stimulator of PGE2 production than epidermal growth factor (EGF), which is known to stimulate prostaglandin production in various cell lines.

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A 72-year-old male who was admitted to our hospital with severe anemia was diagnosed as refractory anemia with ring sideroblasts (RARS), according to the French-American-British (FAB) classification of myelodysplastic syndromes (MDS). The patient showed persistent eosinophilia with no definite signs of either allergy or a parasitic infection. Chromosomal analysis of bone marrow cells revealed inv(16)(p13q22), a known characteristic of M4Eo acute myeloid leukemia (AML) in the FAB classification.

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For a new drug delivery system of 5-fluorouracil, we prepared prodrugs possessing certain desired properties. The prodrugs, 1-(N-4-chlorophenyl-N-methylcarbamoyl)-5-fluorouracil and 1-(N-2,4-dichlorophenyl-N-methylcarbamoyl)-5-fluorouracil, contain high serum albumin binding potency and a comparably long half life in the bloodstream in vivo to Tegafur. These two prodrugs are expected to be retained in the bloodstream as a polymeric complex with albumin and to circulate in the body for a long time, like a polymeric prodrug.

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A 22-year-old woman diagnosed as AML (M3) received myeloablative chemotherapy followed by autologous peripheral stem cell transplantation (PBSCT). Rapid hematopoietic reconstitution occurred. By day 10, the neutrophil count was > 0.

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A 46-year-old man treated with azathioprine (100-150 mg/day) and prednisolone (10mg/day) for 14 years after allogeneic renal transplantation, was admitted to our hospital in December, 1988 for the evaluation of leukocytosis. His leukocyte count was 32,700/microliters with 38% monocytes and 2% blasts. Chromosomal analysis of the bone marrow revealed 45, XY, -7.

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A 56-year-old woman was admitted to our hospital in January, 1990 because of fever and petechiae. Leukocyte count of peripheral blood showed 41,000/microliters with 89% immature cells, and bone marrow was normocellular with 96.2% immature cells.

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The role of phospholipase A2 (PLA2) in the cytotoxic action of tumor necrosis factor (TNF) was examined. Recently, we described the characterization of TNF-resistant sublines isolated from TNF-sensitive cell line L929 (Hayakawa, M., Oku, N.

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For passive targeting of liposomes to tumor tissues, we earlier developed reticuloendothelial system (RES)-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA). In the present study, we encapsulated technetium-99m (99mTc)-diethylenetriaminepentaacetic acid (DTPA) in PGlcUA-liposomes (dipalmitoylphosphatidylcholine:cholesterol:PGlcUA = 40:40:20 as a molar ratio) and studied the biodistribution of the liposomes in tumor-bearing mice. 99mTc-DTPA encapsulated in liposomes effectively accumulated in tumor tissues after intravenous administration.

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In order to establish a noninvasive, quantitative method for measuring regional cerebral blood flow (rCBF) by N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPECT, we attempted to employ continuous venous sampling instead of arterial sampling. Forty two patients with cerebrovascular diseases were classified into two groups, with (group II: n = 35) and without (group I: n = 7) hand warming. In group II, either hand was warmed, wrapping in a hot blanket (group IIA) or immersed in a 44 degrees C water bath (group IIB).

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Because recombinant human granulocyte colony-stimulating factor (G-CSF) has been reported to increase the sensitivity of acute myelogenous leukemia (AML) blast cells to cytosine arabinoside (Ara-C) in vitro, we treated a patient with refractory AML with an Ara-C-based regimen in combination with G-CSF (G-CSF/Ara-C therapy). G-CSF (50 micrograms/m2/day, subcutaneous injection) was administered simultaneously with a continuous intravenous infusion of Ara-C (70 mg/m2/day). Complete remission was achieved, however, severe neutropenia, documented infection, stomatitis, and diarrhea were observed.

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We investigated the effects of long-term therapy with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a 69-year-old man with severe aplastic anemia (SAA). The patient was too old to receive a bone marrow transplantation, and high-dose methylprednisolone and antilymphocyte globulin were ineffective. We administered rhG-CSF in combination with metenolone acetate.

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A 64-year-old female was admitted for treatment of refractory myeloma (IgG-lambda). Because of severe liver cirrhosis, the patient was treated with interferon (IFN) alone (natural IFN 6 x 10(6) IR/day i.m.

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The incidence, number, size, and location of silent cerebral infarction on 0.1 T magnetic resonance imaging was investigated in 66 hypertensive patients (63 +/- 9 years old; mean +/- SD) and 42 age-matched normotensive subjects (61 +/- 9 years old) to determine the clinical significance of hypertension in silent cerebral infarction. Cerebrovascular risk factors and the severity of hypertensive changes in other major target organs were also investigated.

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