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Biomedical subjects

T Okubo

Publications and source records attributed to T Okubo.

At least 199 records · Page 11Linked to original sources
PubMed1997

[Problems of the immunohistochemical differential diagnosis of neuroendocrine carcinoma and neuroblastomas].

Neurons arising from neural tube or neural crest do not express epithelial markers from the beginning of their differentiation and neuroblastomas arising from these anlages also do not express epithelial markers. On the other hand, neuroendocrine carcinomas, such as small cell carcinomas of the respiratory tract, express epithelial markers in addition to neuronal or neuroendocrine markers and demonstration of epithelial marker has been regarded as subtle evidence to rule out neuroblastomas. However, this general rule can not be applied to olfactory neuroblastomas. Unlike neurons derives from neural tube or neural crest, developing neurons arising from the anlage of olfactory nerve, i.e., olfactory placode, have keratin during the embryonic stage. Accordingly, it is unnatural for neoplastic neuroblasts of olfactory placodal origin to have keratin as the embryonic phenotype. In addition, neurons arising from this anlage have an epithelial antigen (EA) detected by Ber-EP4 from the beginning of their differentiation, and this antigen is preserved in the olfactory sensory nerve even in the postnatal stage, though it is lost from the neurons migrating from olfactory placode to brain, i.e., luteinizing hormone-releasing hormone producing neurons (LHRH neurons) during post embryonic stage. Therefore, demonstration of this epithelial antigen in the tumor with neurite formation can be regarded as a satisfactory diagnostic evidence of true olfactory neuroblastoma. LHRH also seems to be a useful marker to determine true olfactory placodal origin of the neuroblastoma. Finally, it is concluded that demonstration of epithelial markers could not be regarded as evidence to rule out neuroblastoma developed in the olfactory nerve region.

Antigens↗
PubMed1997

[Graft-versus-leukemia effect induced by abrupt discontinuation of cyclosporine A following allogeneic bone marrow transplantation].

Cyclosporine A (CyA) was abruptly discontinued in an attempt to induce graft-versus-leukemia (GVL) effect following allogeneic bone marrow transplantation (BMT). It appeared that GVL effect was co-expressed with graft-versus-host disease (GVHD) in 2 of 4 patients and especially minimal residual disease was eliminated during GVHD in a patient with Philadelphia-positive acute lymphocytic leukemia. Subpopulation of cytotoxic T and natural killer cells increased significantly in patients with discontinuation of CyA. This finding suggests that GVL effect was increased following discontinuation of CyA. These results may provide a therapeutic strategy after BMT in patients with high-risk group for relapse of leukemia.

Acute Disease↗
PubMed1997

[A neonate born to a mother with acute promyelocytic leukemia treated by all-trans retinoic acid].

We report a female neonate delivered in week 32 of gestation by a mother who had acute promyelocytic leukemia (APL) treated by all-trans retinoic acid (ATRA). APL was diagnosed in week 29 of gestation and was treated with ATRA from week 30. Physical examination and laboratory tests showed no abnormalities at birth. The girl has since shown normal development, with no peripheral blood abnormalities at 2 years old. Hypersegmented neutrophils, which often appear during ATRA treatment, were seen in the peripheral blood of the mother and cord blood but not peripheral blood of the neonate on the day of birth. ATRA is known to cross the placenta, and has been revealed to be teratogenic in animal studies. There have been eight neonates born to the mothers with APL who were treated with ATRA during pregnancy. All infants, including this one, have shown normal growth without any complications.

Adult↗
PubMed1997

[Surgical analysis for lung cancer in patients younger than 40 years].

Sixteen cases of primary lung cancer in patients younger than 40 years old had been operated on at the department. There were 8 males and 8 females and the male-to-female ratio was 1:1 that was closer than the ratio in elder patients over 40 years. Histologic types were adenocarcinoma in 7 cases, squamous carcinoma in 5 cases, carcinoid in 2 cases, and small cell carcinoma in 2 cases. In younger patients, adenocarcinomas, small cell carcinomas, and carcinoids were more commonly found than squamous cell carcinomas. Patients in stage I, II, and IIIA and those undergoing a curative resection were predominant in cases without any symptoms preoperatively. The 5-year survival rate of the 16 patients younger than 40 years was 42.9%, that was not significantly different from that of elder patients over 40 years old. This relatively better prognosis might be owing to a fact that operated patients were dominantly composed of asymptomatic patients. In younger patients who have good physical status and respiratory function compared with elder patients, aggressive surgical diagnosis followed by resection, if the definitive diagnosis of malignancy is established may contribute to the improvement of prognosis for patients who was suspected of having malignancy.

Adenocarcinoma↗
PubMed1996

Formation of 8-hydroxydeoxyguanosine in calf thymus DNA treated with tert-butylhydroquinone, a major metabolite of butylated hydroxyanisole.

Oxidative DNA damage caused by butylated hydroxyanisole (BHA), 2-tert-butyl(1,4)hydroquinone (TBHQ, a metabolite of BHA) and 2,5-di-tert-butyl(1,4)hydroquinone (DTBHQ), as well as 2,6-di-tert-butyl(1,4)benzoquinone (BHTQ, a metabolite of butylated hydroxytoluene), was evaluated by measuring the formation of 8-hydroxydeoxyguanosine (8OHdG) in calf thymus DNA. 8OHdG formation was greatly increased by TBHQ in a concentration-dependent manner. This effect was strongly enhanced by CuCl2 and suppressed by EDTA, bathocuproinedisulfonic acid disodium salt, methionine, glutathione reduced form or catalase, but was not affected by mannitol, sodium benzoate or sodium azide. Thus, TBHQ-induced 8OHdG formation may be mediated by copper. DTBHQ also induced the formation of 8OHdG, though to a much lesser extent than TBHQ, and its effect was stimulated by CuCl2. BHA had a small enhancing effect at high concentration, only in the presence of CuCl2, whereas in the case of BHTQ, it occurred both in the presence of CuCl2 and FeCl2.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

Interferon-gamma induces Ice gene expression and enhances cellular susceptibility to apoptosis in the U937 leukemia cell line.

The roles of interferons (IFNs) in apoptosis are not fully understood. In this study we show that in the U937 monoblastic leukemia cell line, pretreatment with IFN-gamma enhanced sensitivity to apoptosis triggered by gamma-irradiation or antitumor agents (etoposide or adriamycin), as well as by anti-Fas antibody. In addition, IFN-gamma caused an increased expression of the interleukin-1 beta-converting enzyme (Ice) gene, following strong induction of the interferon regulatory factor-1 (IRF-1) gene, the product of which is a transcriptional activator of the Ice gene. An inhibitor of ICE/Ced-3 family proteases, Z-Asp-CH2-DCB, blocked apoptosis in control cells as well as in IFN-gamma-pretreated cells. These results suggest that enhanced susceptibility of IFN-gamma-pretreated cells to apoptosis is mediated through the induction of Ice by IRF-1. This pathway is not affected by interleukin-1 beta (IL-1 beta) since neutralizing antibody against IL-1 beta failed to suppress the IFN-gamma-mediated enhancement of cell death, and IL-1 beta itself did not mimic the effect of IFN-gamma.

Antibiotics, Antineoplastic↗
PubMed1996

Electrically Induced Shear Waves in Colloidal Crystals

The static light scattering method is used for the detection of acoustic waves induced in colloidal crystals and liquids by low-frequency electric pulses. The method is sensitive to both density and shear modes and can be applied for the study of the liquid-crystalline phase transitions. At low fields the variations of light scattering intensity follow both the amplitude and the phase variations of the wave motion and enable the determination of resonance parameters, hence of viscoelastic parameters of the colloidal system.

Journal Article↗
PubMed1996

Characterization and epitope mapping of several new anti-P-glycoprotein monoclonal antibodies.

Monoclonal antibodies (MAbs) were raised against partially purified Class I P-glycoprotein from multidrug-resistant Chinese hamster ovary CHRB30 cells. Fifteen stable monoclonal hybridoma cell lines were established, and the secreted antibodies were classified into 8 groups on the basis of banding pattern on immunoblots of P-glycoprotein digested with cyanogen bromide or partially digested with proteases. One representative of each group was tested further for several activities. Six of the 8 recognized human P-glycoprotein in the multidrug-resistant SKVLBI cell line. None of the antibodies recognized P-glycoprotein in unfixed cells, suggesting that all recognize cytoplasmic epitopes or extracellular epitopes not accessible in native P-glycoprotein. All 8 antibodies were able to immunoprecipitate P-glycoprotein from non-denaturing detergent solution. The linear epitopes of the antibodies were mapped to 11-27 amino acids. Two of the antibodies had epitopes in the linker region, 3 in the N-terminal nucleotide binding domain, 2 in the C-terminal nucleotide binding domain and 1 in the predicted cytoplasmic loop between predicted transmembrane helices 8 and 9. These antibodies, with known epitopes, could have uses for P-glycoprotein detection, structure/function studies, purification and quantitation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Identification of a novel binding site to the integrin alphaIIbbeta3 located in the C-terminal heparin-binding domain of human plasma fibronectin.

Fibronectin has been shown to bind to integrin alphaIIbbeta3 in Arg-Gly-Asp (RGD)-dependent and -independent manners. A recent study has indicated that a 29-kDa dispase-digestive fragment from the C-terminal heparin-binding domain of human plasma fibronectin (lacking RGD sequence) inhibits binding of fibronectin to thrombin-stimulated platelets and ADP-induced aggregation (Tanabe, J. , Fujita, H., Iwamatsu, A., Mohri, H., and Ohkubo, T.(1993) J. Biol. Chem. 268, 27143-27147). We provide here the evidence that a peptide corresponding to residues from Ala1704 to Glu1718 (designated F1) from this fragment inhibited binding of 125I-labeled 29-kDa fragment of fibronectin to thrombin-stimulated platelets and ADP-induced aggregation. The F1 peptide bound directly to alphaIIbbeta3 integrin receptor. These results indicate that a novel binding site in the C-terminal heparin-binding region of fibronectin is localized within the residues from Ala1704 to Glu1718. Binding of 125I-labeled 29-kDa fragment of fibronectin to thrombin-stimulated platelets was not inhibited by RGDS peptide and the 12-residue peptide from the cell-binding domain of fibronectin, suggesting that binding site in the C-terminal heparin-binding domain may be different from those of RGDS and the 12-residue peptide. This additional alphaIIbbeta3-binding domain(s) in fibronectin may also play some role for prevention of thrombus formation by direct interaction with alphaIIbbeta3.

Adenosine Diphosphate↗
PubMed1996

[Estimation of regional UV-B levels as exposure indices for ecological and environmental epidemiologic studies].

A formula to estimate ground level UV-B from meteorological data was developed for the purpose of utilization in ecologic and/or environmental epidemiologic studies. Estimated values were obtained for various regional points in Japan. There was a very high correlation (r = 0.98) between estimated and observed values at four weather stations during 1991-93. Ranks of the UV-B level for the 1990 year mean and decennial period means during 1961-1989 approximately equated ranks of latitude. However, > or = 10% variation in period means or > or = 10 difference in rank was observed at several regional points. Estimated UV-B level is affected by meteorological conditions including solar radiation and total ozone, and may serve as a refined and improved exposure index compared to conventional indices used in prior studies.

Ecology↗
PubMed1996

[Mortality of chromium plating workers in Japan--a 16-year follow-up study].

Health hazards due to exposure to chromium in the chromium plating industry has been documented in only a few epidemiological studies. A prospective cohort study was conducted to examine the health hazards of chromium plating with a follow-up period of over sixteen years. Subjects were 1193 male metal platers in the small-scale chromium plating plants in Tokyo. They were divided into a chromium plater subgroup (n = 623) and non-chromium plater subgroup (n = 567) and were followed up from October 1976 through December 1992. The 95% confidence interval (95%CI) of the standardized mortality ratio (SMR) was used to evaluate statistical significance. In the chromium plating subgroup, the risk of chronic hepatitis or liver cirrhosis was significantly elevated (SMR 2.34; 95%CI 1.17-4.19) and a trend toward statistical significance was seen for the risk of lung cancer (SMR 1.18; 95%CI 0.99-3.04). No significantly elevated risk was seen in the non-chromium plating subgroup. We concluded that, as the number of disease-specific deaths was small, further follow-up is necessary.

Adult↗
PubMed1996

The novel recognition site in the C-terminal heparin-binding domain of fibronectin by integrin alpha 4 beta 1 receptor on HL-60 cells.

The hematopoietic cell recognition sites of human fibronectin (FN) are the Arg-Gly-Asp-Ser (RGDS) sequence recognized by widely distributed integrin receptor alpha 5 beta 1 and the type III connecting segment (III CS) containing two cell-binding sites, designated CS1 and CS5, that are recognized by the alpha 4 beta 1 receptor. The C-terminal heparin-binding domain of FN (Hep II) has recently been demonstrated to support adhesion of alpha 4 beta 1-dependent melanoma cells [A. P. Mould and M. J. Humphries (1991) EMBO J. 10, 4089-4095]. Previously we demonstrated that this region of FN mediated binding of FN to HL-60 cells (acute promyelocytic leukemia cell line) by direct interaction independently of RGD and CS1 [H. Fujita et al., (1995) Exp. Cell Res. 217, 484-488]. In this study we have characterized a novel site in the Hep II region for binding to HL-60 cells. alpha 4 beta 1 and alpha 5 beta 1 were expressed on HL-60 cells, while alpha 2 beta 1 and alpha 3 beta 1 were not present, as shown by flow cytometry using monoclonal antibodies specific for the different integrins. Anti-alpha 4 beta 1 (P4C2) and anti-beta 1 (JB1a) antibodies inhibited binding of a 29-kDa dispase-digestive fragment of FN to HL-60 cells. This fragment contains the C-terminal heparin-binding domain of FN but lacks CS1 and CS5. Only the peptide representing the sequence from Val1866 to Arg1880, designated E1, inhibited the binding of the 29-kDa fragment to HL-60 cells. The active region of this peptide was a sequence of Thr-Asp-Ile-Asp-Ala-Pro-Ser (TAI-DAPS), which is homologous to Leu-Asp-Val-Pro-Ser (LDVPS) derived from the active site of CS1. Furthermore, labeled E1 peptide directly bound to HL-60 cells. The anti-alpha 4 beta 1 antibody (P4C2) inhibited this interaction. These results indicate that the site of binding to hematopoietic cells is present in the Hep II region of FN and the definition of the chemical structure of FN clarifies a fundamental mechanism of cell invasion of the extracellular matrix.

Amino Acid Sequence↗
PubMed1996

Induction of HIV-1 Nef-specific cytotoxic T lymphocytes by Nef-expressing DNA vaccine.

Recently, some individuals who have remained seronegative despite definite exposure to HIV-1 have been reported. Among these individuals, an unusually high frequency of HIV-1 Nef-specific cytotoxic T lymphocytes was observed. Direct injection of plasmid DNA encoding foreign antigen can elicit both cell-mediated immunity and antibody responses (DNA vaccine). We constructed an HIV-1 Nef-expressing plasmid, and we induced HIV-1 Nef-specific cytotoxic T lymphocytes. This is the first report of inducing HIV-1 Nef-specific cytotoxic T lymphocytes by DNA vaccine.

Amino Acid Sequence↗
PubMed1996

Role of superoxide anions in airway hyperresponsiveness induced by cigarette smoke in conscious guinea pigs.

To investigate the involvement of superoxide in airway hyperresponsiveness and bronchoconstriction induced by cigarette smoke (CS), we evaluated the effects of superoxide dismutase (SOD), a scavenger of superoxide anion, and apocynin, an inhibitor of superoxide anion-generating NADPH oxidase in phagocytes, on the airway responses induced by CS in conscious guinea pigs. Airway responsiveness was assessed by PC200Mch, the concentration required to produce a doubling in the baseline specific airway resistance (sRaw) to an inhaled methacholine aerosol, in nonanesthetized spontaneously breathing animals. Before being exposed to ten puffs of CS, animals inhaled either SOD (5,000 units/ml or 25,000 units/ml) or vehicle. Although SOD did not affect PC200Mch in the air control group, this agent significantly reduced the CS-induced airway hyperresponsiveness. Repeated administration of apocynin (12 mg/kg for 4 days) did not affect PC200Mch after exposure to CS. These data suggest that the superoxide from CS was involved in the airway hyperresponsiveness induced by CS, whereas phagocytic reactive oxygen species were not. The data also suggest a potential therapeutic role for antioxidants in airway hyperresponsiveness.

Acetophenones↗
PubMed1996

Affinity of Fibrinogen Binding to Platelet Membrane Glycoprotein IIb/IIIa Increases with RGDS and gamma Chain Fibrinogen Peptide Hybrid.

Arg-Gly-Asp (RGD)-containing peptides and the peptide unique to fibrinogen in the C-terminal domain of the gamma chain are important for fibrinogen binding to platelet membrane glycoprotein (GP) II b/III a. We synthesized a unique hybrid peptide of YRGDSPLGGAKQAGDV encompassing the RGD sequence (RGDS) with the gamma chain peptide (LGGAKQAGDV). Maximum binding to thrombin-stimulated platelets was achieved within 40 minutes with the YRGDS peptide and within 20 minutes with the hybrid peptide and native fibrinogen. The platelet binding sites were 58,600 molecules with the hybrid peptide and 52,400 molecules with YRGDS. These peptides inhibited fibrinogen binding to thrombin-stimulated platelets in a dose-dependent manner. The order of inhibitory potency of these peptides was as follows: fibrinogen models R: hybrid peptide > YRGDS > GQQHHLGGAKQAGDV (G15). The RGES peptide had no inhibitory activity. These three peptides inhibited binding of the anti-GP II b/III a monoclonal antibody (LJ-CP8) to platelets. The hybrid peptide showed the most potent inhibitory activity, with an IC50 of 48 µM. These results suggest that the linear combined RGDS and gamma chain peptide created with proline increases the affinity of binding to activated platelets.

Journal Article↗