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Biomedical subjects

T Okubo

Publications and source records attributed to T Okubo.

At least 145 records · Page 8Linked to original sources
PubMed1998

Acute myelomonoblastic leukemia carrying the PEBP2beta/MYH11 fusion gene.

As recurrent chromosome abnormalities in leukemia are highly associated with particular subtypes, the genetic events of specific chromosome alteration must be associated with leukemogenesis and characteristics of the disease. The chromosomal breakpoints involved in inv(16) and t(16;16) have been shown to generate the fusion gene PEBP2beta(CBFbeta)/MYH11. The PEBP2beta/MYH11 fusion transcripts in all 8 patients with M4Eo, 2 of 18 with M4, and one CML in the blastic phase were detected by using RT-PCR and Southern blotting. We demonstrated the marked expression of CD34 and c-KIT (CD117) antigens in myelomonoblastic leukemia cells from all patients carrying this fusion gene, which was in contrast to the patients with M4 but without the fusion gene. These results indicate that immunophenotypic analysis is useful for detection of leukemia with the fusion gene, and that the PEBP2beta/MYH11 fusion gene is involved in immature cells expressing CD34 and c-KIT antigens.

Artificial Gene Fusion↗
PubMed1998

Residual leukemic cell counts in the bone marrow at the end point of intensive induction therapy may be a prognostic factor for acute myeloblastic leukemia in adults.

Between January 1990 and May 1994, 59 previously untreated adult patients with acute myeloblastic leukemia (AML) were treated with a combination of behenoyl-cytosine-arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP) and prednisolone (PSL). Forty one patients (69.5%) achieved complete remission (CR). The Kaplan-Meier analysis revealed an actuarial probability for remaining in remission of 36% in patients who achieved remission and a survival of 29% in all patients at 5 years. A favorable factor relative to achieving CR was performance status (P=0.04). In addition the presence of 300 cells/microl or less of residual leukemic cell counts in the bone marrow at the end point of induction therapy tended to favor remission (P=0.06) using the multivariate analysis with a multiple logistic regression model. In addition the residual leukemic cells counts of less than 300/microl in the bone marrow at the end point of induction therapy was the most significant factor for durable remission (P=0.05) by the Cox's proportional hazard model. We concluded that residual leukemic cells counts in the bone marrow at the end point of intensive induction therapy is a valuable prognostic factor for adults receiving response-oriented individualized induction therapy for AML.

Adolescent↗
PubMed1998

[Chronic myelogenous leukemia with long-term hypoplasia induced by alpha-interferon and hydroxyurea].

A 48-year-old woman was admitted with chronic myelogenous leukemia in November, 1996 and was treated with hydroxyurea (HU), because of marked leukocytosis; WBC 404,000/microliter. On January 29, 1997, administration of HU was stopped, and treatment of alpha-interferon (IFN alpha) was started with 6x 10(6)U, every day. However, the WBC count rose from 19,600/microliter to 56,800/microliter, and the combination of IFN and 2,000 mg of HU was started on February 4. The dose of HU was reduced to 500 mg on February 27, and the IFN administration was reduced to 3 times a week from April 4, because the WBC count was less than 10,000/microliter. Pancytopenia was revealed in May. The bone marrow biopsy specimen demonstrated marked hypoplastic changes, and chromosome analysis of bone marrow cells showed Philadelphia chromosome in all 20 metaphases. Treatment was interrupted for 7 months, but hematologic parameters did not recover. There were 9 cases reported in detail with bone marrow hypoplasia induced by IFN. One patient received IFN alone and 8 patients received anti-cancer drugs before treatment of IFN. We concluded that great care must be taken for IFN treatment of CML.

Antineoplastic Agents↗
PubMed1998

Intranasal administration of demopressin (DDAVP) for type 1 and type 2A von Willebrand disease.

Desmopressin was administered intranasally to seven patients with von Willebrand disease (type 1: 4 patients, type 2A: 3 patients) to assess the response and safety. von Willebrand factor antigen ranged from 8% to 60% before treatment and increased significantly after intranasal DDAVP administration (the median relative increase: two- to threefold). Factor VIII levels also increased substantially over baseline levels after intranasal administration. Before treatment ristocetin cofactor activity was 32 +/- 12% in patients with type 1 vWD and 9 +/- 5% in patients with type 2A vWD. After intranasal administration, the levels of ristocetin cofactor activity increased to 56 +/- 21% and 29 +/- 9%, respectively. The bleeding time was normalized in 86% of the patients. The abnormality of vWF multimers in type 1 vWD returned more or less to normal after intranasal DDAVP administration whereas that in type 2A vWD did not. The intranasal administration of DDAVP is safe and effective for minor bleeding episodes and is adaptable for home use in patients with type 1 and type 2A vWD.

Administration, Intranasal↗
PubMed1998

[Investigation for polymorphism of ALDH2 exon12 in several Asian areas].

Mitochondrial aldehyde dehydrogenase (ALDH2) shows genetic polymorphism (Glu487Lys substitution) among Mongoloid populations, and the substitution is responsible for flushing symptom after alcohol intake. Recently, new ALDH2 alleles (ALDH2*3 and ALDH2*2Taiwan) in exon12 were reported in North American Indians and in Chinese from Taiwan by Novoradskey et al (1995). In the present study, we investigated the new allelic variants in exon12 for the five different ethnic groups (Mongolian, North Chinese, South Chinese, Myanmar, Japanese) by using PCR-SSCP and PCR-direct sequencing. Also, Glu 487 Lys substitution was analyzed to obtain additional information on gene geography of ALDH2 alleles in Asia reported so far. No new variants were found in the five population groups, but ALDH2*2 allele showed different frequencies among these groups. Especially, the frequencies of ALDH2*2 in Myanmer (0.02) and Mongolian (0.05) were significantly lower than other populations.

Aldehyde Dehydrogenase↗
PubMed1998

[A case report on surgery for chylothorax after anterior spinal fusion: usefulness and effectiveness of intraoperative milk administration and postoperative OK-432 administration].

A 75-year-old man of chylothorax after anterior spinal fusion successfully underwent thoracoabdominal operation in order to ligate chyloleakage. Not only preoperative milk intake but also intraoperative administration of milk through nasogastric tube was useful for identification of the site of leakage. OK-432 was administered through locally placed and chest tube after operation, after which residual chyloleakage was stopped. lntraoperative administration of milk through nasogastric tube was useful and OK-432 injection through topical and chest tube may be effective, these should be recommended for management of chylothorax.

Aged↗
PubMed1998

[A successful case report on intralesional OK-432 therapy for cystic mediastinal lymphangiomas].

A 42-years-old female was referred to the university hospital because of cystic lesions of the right superior mediastinum. Drainage tube was found at right supraclavicular fossa with prolonged lymphatic discharge. We diagnosed this case as a benign cystic lymphangiomas with CT scan and CT scan with cystography and chemical analysis of the contents of the cyst. Intralesional OK-432 therapy for cystic mediastinal lymphangioma was performed. OK-432 was administered through intralesionally placed drainage tube. Excellent result was obtained. A few weeks later, residual lymphatic discharge through drainage tube became stopped. No expansion of the mediastinal cyst was found after drainage tube removal. Intralesional OK-432 therapy for cystic mediastinal lymphangioma was very effective and useful, it should be recommended for the management of the first choice of therapeutic method for cystic mediastinal lymphangioma because of no neurological deficit after this treatment.

Adult↗
PubMed1998

[Surgical analysis for metastatic lung tumor from renal cell carcinoma].

Metastatic lung tumor from renal cell carcinoma were studied in 29 cases. Eighteen patients were treated surgically, 11 were treated non-surgically. The overall 5-year survival rate with the patients of pulmonary resection was 53.5%, and that with those of conservative therapy was 0%, and this difference is statistically significant (p < 0.05). There was no significant difference in any characteristics such as sex, age, stage, grade, disease free interval, metastatic pattern and combination with or without interferon therapy. There was no significant difference in surgically treated patients with pulmonary metastasis in terms of any factors such as age, sex, stage, grade, disease free interval, pulmonary metastasis pattern, metastatic number, surgical procedure, combination with or without interferon therapy statistically. Analysis for the surgically treated patients with pulmonary metastasis from renal cell carcinoma shows no significant difference in prognosis with any characteristics. This result shows efficacy of surgery even if for the patients with synchronous bilateral multiple pulmonary metastasis from renal cell carcinoma.

Adult↗
PubMed1998

[Fulminant hepatic failure related to immunosuppressive therapy in an asymptomatic HBsAg carrier with idiopathic interstitial pneumonia].

A 72-year-old woman who was an asymptomatic HBsAg carrier was admitted because of productive cough and dyspnea on exertion. After close examination, she was given a diagnosis of idiopathic interstitial pneumonia (IIP), and treated with glucocorticoids and cyclophosphamide. However, fulminant hepatitis type B developed and the patient died of respiratory complications stemming from the acute exacerbation of IIP. To avoid such outcomes, extra caution should be taken when planning immunosuppressive therapy for HBsAg carriers.

Aged↗
PubMed1997

Simultaneous determination of catechins in human saliva by high-performance liquid chromatography.

Green tea extracts have been suggested to possess a preventive effect against dental caries. A quantitative method for their anticariogenic substances, catechins, was developed to evaluate their concentrations in human saliva after mouthrinsing with green tea extract. Salivary catechins were extracted to the organic phase after forming a complex with diphenylborate and an ion-pair with tetra-n-butylammonium, and then back-extracted to the acidic aqueous phase. The extract was analyzed by high-performance liquid chromatography using diode array detection at absorption wavelengths ranging from 269 to 278 nm. In reversed-phase chromatography by a gradient elution, eight catechins originating from green tea and an internal standard were separated in 15 min without interfering peaks. All the catechins were simultaneously and selectively determined in the concentration range 0.05-25.0 microg/ml. In replicate spiking experiments with standards, the mean recovery ranged between 86 and 99%, and both intra- and inter-assay C.V.s were within 2.3%. When mouthrinsing with an aqueous solution of green tea extract (5.0 mg/ml) containing eight catechins, the quantitative results revealed that each catechin was retained at microg/ml levels in saliva for up to 60 min.

Catechin↗
PubMed1997

Transcriptional regulation of the human monocyte chemoattractant protein-1 gene. Cooperation of two NF-kappaB sites and NF-kappaB/Rel subunit specificity.

Human monocyte chemoattractant protein-1 (human MCP-1) mRNA accumulated in THP-1 cells 2 h after lipopolysaccharide (LPS) stimulation. DNase I footprinting revealed that LPS stimulation induced protein binding to the two closely located NF-kappaB sites, A1 and A2. By electrophoretic gel mobility shift assay and supershift assay, the binding of (p65)2, c-Rel/p65, p50/p65, and p50/c-Rel to the A2 oligonucleotide probe was detected after LPS stimulation. In contrast, 12-o-tetradecanoylphorbol 13-acetate did not induce a significant amount of MCP-1 mRNA in THP-1 cells 2 h after stimulation, and only p50/p65 bound to the A2 probe. trans-Activity of each NF-kappaB/Rel dimer was investigated by transfecting P19 cells with p65, p50, and/or c-Rel expression vectors, and a luciferase construct containing the enhancer region of the human MCP-1 gene. Expression of recombinant p65 or p65 and c-Rel resulted in elevated luciferase activities, indicating that (p65)2 and c-Rel/p65 had trans-activity. The binding of (p65)2 and/or c-Rel/p65 to the A2 probe was also detected from 12-o-tetradecanoylphorbol 13-acetate-stimulated HeLa, HOS, and A172 cells in which expression of MCP-1 mRNA was elevated. Finally, the role of the A1 site was investigated. Both (p65)2 and c-Rel/p65 bound to the A1 probe by electrophoretic mobility shift assay and a mutation in the A1 or A2 site resulted in a loss of the enhancer activity. These results suggest that the binding of (p65)2 and c-Rel/p65 to the A1 and A2 sites of this gene is important for the tissue- and stimulus-specific transcription of the human MCP-1 gene.

Base Sequence↗
PubMed1997

A synthetic peptide, FN-C/H-V, from the C-terminal heparin-binding domain of fibronectin promotes adhesion of PMA stimulated U937 cells.

Hematopoietic cells differentially bind to the C-terminal heparin-binding domain of fibronectin depending on the activation state of integrin alpha 4 beta 1. In this study, we have identified a synthetic peptide derived from the C-terminal heparin-binding domain of fibronectin that promotes adhesion of PMA-treated U937 cells (a monocytic cell line) in a dose-dependent manner. A peptide (FN-C/H-V; residues Gln1892 to Gly1910) was active to inhibit adhesion of PMA-treated U937 cells to the 29-kDa fragment comprising the C-terminal heparin-binding domain of fibronectin. A peptide with scrambled version of FN-C/H-V lost the inhibitory activity on the adhesion. Furthermore, the IgG-conjugated FN-C/H-V promoted the adhesion of PMA-treated U937 cells to an extent comparable to that of the 29-kDa fragment. The adhesion of PMA-treated U937 cells on IgG-conjugated FN-C/H-V was inhibited both by anti-alpha 4 beta 1 antibody and by glycosaminoglycans including chondroitin sulfate and heparan sulfate. The other peptide, FN-C/H-II, was also a weak adhesion-promoting domain. These results suggest that the amino acid sequence defined by peptide FN-C/H-V contributes to the main adhesion-promoting activity of the 29-kDa fragment of fibronectin to stimulated U937 cells. The regulation of interactions of alpha 4 beta 1 integrin and glycosaminoglycans with ligands in fibronectin may have important implications for the migration and function of U937 cells.

Amino Acid Sequence↗
PubMed1997

Kinetic Analyses of the Colloidal Crystallization of Silica Spheres As Studied by Reflection Spectroscopy

Reflection spectroscopy is used in kinetic analyses of the nucleation and growth processes of colloidal crystals of silica spheres (110 nm in diameter) in exhaustively deionized aqueous suspensions. Sphere concentrations range from 0.001 to 0.0025 in volume fraction (phi) for the nucleation and 0.0014 to 0.0036 for the crystallization process, respectively. Induction periods are from 1 to 500 s and become longer with decreasing sphere concentration. Nucleation rates are 10(-3) to 10(3) &mgr;m-3 s-1 and increase sharply as sphere concentration increases. The crystallization process has been observed through the sharpening and the increase of intensity in the reflection peaks for the suspension in a test tube, which stands still after being inverted. Crystal growth rates v range from 2 to 15 &mgr;m/s and decrease linearly as the reciprocal sphere concentration increases. Crystal growth rates represented by the number of unit cells u also increase as phi increases, ranging from 2 to 23 unit cells/s. The importance of electrostatic intersphere repulsion through electrical double layers and of cooperative fluctuation of colloidal spheres in crystallization processes is supported. Copyright 1997Academic Press

Journal Article↗
PubMed1997

CPP32 activation during dolichyl phosphate-induced apoptosis in U937 leukemia cells.

Treatment of U937 cells with dolichyl phosphate led to an increase in the activity of the ICE family protease CPP32, accompanied with cleavage of pre-CPP32 to generate p17. Peptide inhibitors YVAD-cmk and Z-Asp-CH2-DCB (specific to ICE) and DEVD-CHO (specific to CPP32) blocked the dolichyl phosphate-induced apoptosis. The dolichyl phosphate-induced increase of CPP32 activity was inhibited by adenylate cyclase inhibitors, SQ 22536 and 2',5'-dideoxyadenosine. Dolichyl phosphate caused a transient increase of intracellular cAMP concentration. The results suggest that modulation of cAMP synthesis due to the stimulation of adenylate cyclase by dolichyl phosphate plays a critical role in CPP32 activation and apoptosis.

Adenine↗
PubMed1997

Enhancement of cell-mediated immunity against HIV-1 induced by coinnoculation of plasmid-encoded HIV-1 antigen with plasmid expressing IL-12.

Previous investigations have demonstrated that CTL may play an important role in suppressing the disease progression of HIV infection. In this study, we inoculated mice with IL-12 expression plasmid together with plasmid-encoding HIV-1 envelope to enhance CTL activity by activating a Th1-type response. The results of delayed-type hypersensitivity using the footpad swelling response and of CTL activity clearly showed that HIV-1-specific cell-mediated immunity was enhanced by inoculation of the IL-12 expression plasmid. Quantitation of cytokine in the sera of IL-12-inoculated mice revealed that IFN-gamma significantly increased. The enhanced cell-mediated immunity responses were abrogated by combined administration of the IL-12 expression plasmid and neutralizing anti-IFN-gamma Ab. Together, these results suggest that enhanced virus-specific cell-mediated immunity occurred via an endogenously produced IFN-gamma by inoculation of IL-12 expression plasmid.

AIDS Vaccines↗
PubMed1997

Contribution of oxygen radicals to DNA cleavage by quinone compounds derived from phenolic antioxidants, tert-butylhydroquinone and 2,5-di-tert-butylhydroquinone.

The effects of synthetic phenolic antioxidants, tert-butylhydroquinone (TBHQ), 2,5-di-tert-butylhydroquinone (DTBHQ) and 3-tert-butyl-4-hydroxyanisole (BHA), on DNA cleavage were examined with supercoiled plasmid DNA, pUC18, in vitro. Extensive single and double strand breaks of DNA by TBHQ were observed and almost all the DNA was converted to the linear form at 10(-2) M. The cleavage was stimulated by both CuCl2 and FeCl2, though the effect of FeCl2 was smaller. Metal ion chelators and some oxygen radical scavengers inhibited the cleavage. The generation of TBHQ semiquinone radical and hydroxyl radical in the presence of copper was demonstrated by ESR spectroscopy. DTBHQ also caused DNA cleavage, though its effect was much smaller than that of TBHQ. BHA had no effect in the experimental systems employed. Oxygen radicals were considered to contribute to the DNA cleavage by TBHQ and DTBHQ.

Animals↗
PubMed1997

Immunomodulatory effects of a plasmid expressing B7-2 on human immunodeficiency virus-1-specific cell-mediated immunity induced by a plasmid encoding the viral antigen.

B7 co-stimulation is essential for activating resting T cells following antigen recognition by the T cell receptor. To determine whether B7 has adjuvant activities on human immunodeficiency virus type-1 (HIV-1)-specific immunity induced by inoculation of a plasmid encoding HIV-1 env and rev (DNA vaccine), B7-1 and B7-2 expression plasmids were co-inoculated with the DNA vaccine. The delayed-type hypersensitivity response and cytotoxic T lymphocyte (CTL) activity were significantly enhanced when B7-2 expression plasmid was co-inoculated with the DNA vaccine, but were unaffected when the B7-1 expression plasmid was used with the vaccine instead. The immunological response enhanced by B7-2 decreased below the level of mice immunized with the DNA vaccine in combination with CTLA4Ig, an inhibitor of the B7/CD28 co-stimulatory signal, suggesting that this signal is critical for the enhanced response induced by co-inoculation of the DNA vaccine and B7-2 expression plasmid. This enhancement appeared to occur via an interferon-gamma (IFN-gamma)-dependent mechanism, as combined administration of the B7-2 plasmid and neutralizing anti-IFN-gamma antibody abrogated the virus-specific cell-mediated immunity. These results suggest that this gene-based co-inoculation strategy using HIV-1 viral antigen and B7-2 co-stimulatory molecule could be a powerful means of combating HIV-1 infection.

AIDS Vaccines↗