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Biomedical subjects

T Okubo

Publications and source records attributed to T Okubo.

At least 19 recordsLinked to original sources
PubMed1999

Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP2alphaB gene associated with myeloblastic leukemias.

The AML1 gene encoding the DNA-binding alpha-subunit in the Runt domain family of heterodimeric transcription factors has been noted for its frequent involvement in chromosomal translocations associated with leukemia. Using reverse transcriptase-polymerase chain reaction (RT-PCR) combined with nonisotopic RNase cleavage assay (NIRCA), we found point mutations of the AML1 gene in 8 of 160 leukemia patients: silent mutations, heterozygous missense mutations, and biallelic nonsense or frameshift mutations in 2, 4, and 2 cases, respectively. The mutations were all clustered within the Runt domain. Missense mutations identified in 3 patients showed neither DNA binding nor transactivation, although being active in heterodimerization. These defective missense mutants may be relevant to the predisposition or progression of leukemia. On the other hand, the biallelic nonsense mutants encoding truncated AML1 proteins lost almost all functions examined and may play a role in leukemogenesis leading to acute myeloblastic leukemia.

Adult↗
PubMed1999

Kinetic Analyses of Colloidal Crystallization in a Sinusoidal Electric Field as Studied by Reflection Spectroscopy.

The effect of a sinusoidal electric field on crystal growth rates in the colloidal crystallization of silica spheres (110 nm in diameter) in exhaustively deionized aqueous suspensions has been studied by reflection spectroscopy. Sphere concentration is 0.0016 in volume fraction. Nucleation time is shorter than 1 s. The crystal growth rates, v, of the body-centered cubic lattices have been determined from the increase in the cube root of the intensity in the sharpened reflection peaks. The v value is 20 µm/s in the absence of an electric field. v decreases from 20 to 8 µm/s as the voltage applied increases from 0 to 10 V at 1 Hz. v decreases from 30 to 15 µm/s when frequency increases from 0.01 to 10 Hz at E = 6 V, and remains constant irrespective of frequencies higher than 10 Hz up to 10 kHz. Interestingly, the crystallization of bcc lattices is enhanced at low frequencies between 0.01 and 0.5 Hz. The main causes for the retardation of crystallization at high frequencies and voltages are (a) the additional translational fluctuation of the spheres and the surrounding electrical double layers by the electric field, and (b) the partial melting of the crystals by the shearing forces in an electric field. The importance of electrostatic intersphere repulsion resulting from overlap of the electrical double layers and cooperative and synchronized fluctuation of colloidal spheres in crystallization processes is strongly supported. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Nested case-control study of esophageal cancer in relation to occupational exposure to silica and other dusts.

BACKGROUND: Standardized proportionate mortality ratio (SPMR) was found to be 2.2 (95% CI = 1.3-3.5) for esophageal cancer (EC) among workers exposed to refractory brick dust in a large iron-steel complex in China. METHODS: A nested case-control design within a cohort of industrial workers. One hundred and twenty-five EC cases and 250 controls were identified from the death registry file. Interviews were conducted of the next of kin for past exposure information on job, domestic, and lifestyle factors. History of occupational exposure to various dusts was reconstructed from personnel files and by interviewing colleagues utilizing a job-exposure matrix. RESULTS: After adjusting for confounders, occupational exposure to silica dust was the most important risk factor among all variables investigated, with a 2.8-fold risk and a clear dose-response by length of exposure. Alcohol drinking (OR = 1.8) and coal cooking (OR = 2.0) were risk factors and high consumption of fruit diet (OR = 0.5) and meat diet (OR = 0.6) were protective factors. CONCLUSIONS: The relationship between occupational exposure to silica dust and the risk of EC found in an earlier SPMR study was confirmed. Ingestion of silica particles after lung clearance may increase the risk of EC among workers exposed to silica.

Aged↗
PubMed1999

A study on the effects of endogenous nitric oxide on coronary blood flow, myocardial oxygen extraction and cardiac contractility.

The purpose of the present study was to clarify how endogenous nitric oxide (NO) affects cardiac contractility and myocardial oxygen consumption (MVO2) in vivo. alpha-Chloralose-anesthetized dogs (n = 18) were instrumented to perform continuous and simultaneous measurements of coronary blood flow (CBF), anterior interventricular vein oxygen saturation (with the use of a fiberoptic catheter), aortic pressure, left ventricular pressure, and left ventricular volume. CBF, myocardial oxygen extraction (O2-extract), MVO2, the relationship between CBF and O2-extract during direct vasodilation induced by intracoronary papaverine (0.1, 0.2, 0.4 mg/kg), and cardiac contractility (Emax) were examined at control, after intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA, 2 mg/kg) and after antagonization of NO by L-arginine (20 mg/kg). L-NMMA decreased CBF from 62.0 +/- 1.7 to 59.7 +/- 2.4 (mL/min/100 g, P < 0.05) and increased O2-extract from 68.2 +/- 1.7 to 79.0 +/- 1.7% (P < 0.05). Emax was increased after L-NMMA from 3.2 +/- 0.2 to 3.7 +/- 0.1 (mmHg/mL/100 g, P < 0.05). These effects of L-NMMA were antagonized by L-arginine (P < 0.05 vs. after L-NMMA, P = NS vs. before L-NMMA). L-NMMA shifted CBF and O2-extract relationship determined by papaverine injection upward and L-arginine antagonized it to its baseline level. Endogenous NO reduces cardiac contractility and decreases MVO2, while increasing CBF.

Animals↗
PubMed1999

Superoxide mediates cigarette smoke-induced infiltration of neutrophils into the airways through nuclear factor-kappaB activation and IL-8 mRNA expression in guinea pigs in vivo.

We examined the hypothesis that superoxide mediates infiltration of neutrophils to the airways through nuclear factor (NF)-kappaB and interleukin-8 (IL-8) after acute exposure to cigarette smoke (CS) in vivo. Male Hartley strain guinea pigs were exposed to air or 20 puffs of CS and killed 5 h after the exposure. The differential cell count of bronchoalveolar lavage fluid and specific myeloperoxidase enzyme assay demonstrated that acute exposure to CS caused neutrophil accumulation to the airways and parenchyma, respectively. Acute exposure to CS increased DNA-binding activity of NF-kappaB in the lung. Acute exposure to CS also increased IL-8 messenger RNA (mRNA) expression in the lung. Pretreatment of guinea pigs with recombinant human superoxide dismutase (rhSOD) aerosols reduced the CS-induced neutrophil accumulation to the airways. Both activation of NF-kappaB and increased IL-8 mRNA expression were also inhibited by the pretreatment of rhSOD aerosols. Strong immunoreactivities for p65 and p50 were detected in the nuclei of alveolar macrophages after acute exposure to CS. The signal for IL-8 mRNA expression was demonstrated in the alveolar space after acute exposure to CS. Neither significant immunoreactivities for p65 and p50 nor IL-8 mRNA signals were observed in airway epithelium. These observations suggest that acute exposure to CS initiates superoxide-dependent mechanism that, through NF-kappaB activation and IL-8 mRNA expression, produces infiltration of neutrophils to the airways in vivo. It was also suggested that the alveolar macrophage is one potential source of NF-kappaB activation and IL-8 mRNA expression after acute exposure to CS.

Animals↗
PubMed1999

Modified Fontan operation. Considerations for the determination of the appropriate procedure.

BACKGROUND: Although the surgical results of the modified Fontan operation continues to improve, there are various advantages and disadvantages in terms of the post operative condition associated with the Fontan modifications. Late morbidity and mortality are mainly due to arrhythmias, thromboembolic complications, systemic venous hypertension and infective endocarditis. We reported our experience of the modified Fontan operation to determine an appropriate procedure for each patient. METHODS AND RESULTS: Seven patients (ranging from the age 1-14 years) underwent a modified Fontan operation including a lateral tunnel (n = 1), extracardiac conduit (n = 2) and autogenous atrial tunnel (n = 4). There was one hospital death due to sepsis in which the patient underwent lateral tunnel procedure. The mean follow up of another six patients was 20 months (ranging from 1-39 months) and all patients were classified as NYHA class I, and remained in normal sinus rhythm without any thromboembolic complications. CONCLUSIONS: When using the autogenous atrial tunnel, there are potential advantages; it is not associated with thromboembolism or endocarditis and has growth potential. However, in high-risk patients with increased pulmonary vascular resistance, impaired ventricular function and pre-operative atrial arrhythmias, it appears reasonable to use an extracardiac conduit.

Adolescent↗
PubMed1998

Electro-optic Properties of Colloidal Crystals As Studied by Reflection Spectroscopy.

Electro-optic properties of colloidal crystals of silica spheres in the exhaustively deionized aqueous suspension have been studied by the reflection spectroscopy using a T-type cell. Acoustic shear waves are induced when sine-wave electric fields ranging from 0.01 to 1 Hz are applied. Modulation effects of the crystals on the applied AC fields such as phase delay, change in response intensity, waveform transformation, and harmonics generation are observed. The shear waves propagate outside the electrodes where the electric field is absent. The synchronous fluctuation of the colloidal spheres including expanded electrical double layers in the crystal lattice will be one of the main causes of the electro-optic nature of the crystals. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Surface Tension of Biological Polyelectrolyte Solutions.

Surface tensions, gamma, of biological polyelectrolytes in aqueous solutions are studied systematically as possible at the air-water interface by the Wilhelmy method. The polyelectrolytes measured are sodium chondroitin sulfates A (NaCRA) and C (NaCRC), sodium poly-alpha,l-glutamate (NaPGA), poly-l-lysine hydrobromide (PLL . HBr), deoxyribonucleic acid (DNA), lysozyme (LZ), and bovine serum albumin (BSA). Linear-type macroions such as NaCR, NaPGA, PLL . HBr, and DNA have no surface activity in a wide range of polymer concentrations below the critical polymer concentration, m*, and increases as the concentration increases above m*. Surface activity of the undissociated state of macroions is rather high in general. Globule-like macroions such as LZ and BSA show high surface activity at isoelectric point above m* accompanied with orientation of the molecules along the air-water interface. Separation into the hydrophobic and hydrophilic parts at the interface and balancing in their strength are important for appearance of surface activity. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Novel mutations in the promoter and coding region of the human 5-HT1A receptor gene and association analysis in schizophrenia.

Dysfunction of serotonin systems has been implicated in schizophrenia. In the present study, the human 5-HT1A receptor gene containing the 5' untranslated region was screened in order to detect genetic variations, through which alteration of protein function or level of expression might contribute to schizophrenia. Genomic DNAs were isolated from whole-blood samples of 61 unrelated schizophrenic patients and 100 healthy controls. Genetic variations were screened systematically by single-strand conformational polymorphism (SSCP) analysis, followed by direct sequencing of polymerase chain reaction (PCR) product as well as restriction fragment-length polymorphism (RFLP). The novel mutations (-51T --> C, -152C --> G, -321G --> C, -480delA, and -581C --> A) were found in the 5' untranslated region. Furthermore, we found a novel missense mutation (Gly272Asp) in the coding region in addition to the mutations (Pro16Leu, 294G --> A, and 549C --> T) reported previously. No significant differences in genotype frequencies as well as allele frequencies were found between patients and controls. Our data provided no evidence of association between schizophrenia and the variants in the 5' untranslated region as well as the coding region of the human 5-HT1A receptor gene.

Genetic Markers↗
PubMed1998

Kinetic Analyses of Colloidal Crystallization in Alcoholic Organic Solvents and Their Aqueous Mixtures As Studied by Reflection Spectroscopy.

Reflection spectroscopy is used for the kinetic analyses of the nucleation and growth process of colloidal crystals of silica spheres (110 nm in diameter) in exhaustively deionized suspensions of purely alcoholic organic solvents (methyl alcohol, ethyl alcohol, and ethylene glycol) and aqueous mixtures with alcohols (methyl, ethyl, n-propyl, and n-butyl alcohols and ethylene glycol). Sphere concentrations studied range from 0.001 to 0.01 in volume fraction, rather high compared with those in water. Induction periods are from 5 to 2000 s and are prolonged with decreasing sphere concentration. Nucleation rates are 10(-3) to 10(3) mm-3 s-1 and increase sharply as sphere concentration increases. The crystal growth rates, v have been determined from the increase of intensity in the sharpened reflection peaks. Values of v range from 1 to 27 µm/s and decrease linearly as the reciprocal sphere concentration increases. Nucleation and crystallization rates decrease sharply as the fraction of the organic solvents increases in the mixtures with water. The importance of the electrostatic intersphere repulsion through the electrical double layers and the cooperative and synchronized fluctuation of colloidal spheres in the crystallization processes is supported. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

[Research on the contents of material safety data sheets].

The Material Safety Data Sheet (MSDS) system for the safe management of chemical substances was officially promulgated in 1993 and has been gradually put into practice through administrative guidance in Japan. However, little research has been done on the quality of such data sheets provided from various sectors of industries. We examined two sets of MSDSs obtained from a refractory ceramic plant. In the first survey in 1995, the set of MSDSs was from July, 1992 to March, 1994; and in the second survey in 1997, the set was from April, 1994 to November, 1996. The number of MSDSs examined in these two surveys was 159 and 81, respectively. The number of MSDSs in which "Hazard Identification" was indicated was 100 (63%) in the 1995 survey and 75 (93%) in the 1997 survey. The number of those in which "Toxicological Information (Stability and Reactivity)" was indicated was 81 (51%) and 80 (99%), respectively. The description rates for the essential items, including the above two, were found to be improving.

Data Collection↗
PubMed1998

Clinical significance of inhibitors in acquired von Willebrand syndrome.

Of 260 patients enrolled, 25 patients (9.6%) were associated with acquired von Willebrand syndrome (AvWS). We studied 25 patients with AvWS, retrospectively. AvWS was diagnosed by reduced levels of von Willebrand factor (vWF) (decrease of von Willebrand factor antigen [vWF:Ag] and von Willebrand ristocetin cofactor [vWF:RCoF]), a decrease of ristocetin-induced platelet agglutination (RIPA), sometimes decreased high-molecular-weight multimers, and prolonged bleeding time with neither prior nor family histories of bleeding problems and the evidence of normal vWF:RCoF in their families. The inhibitor of vWF was determined by mixing patient plasma with pooled normal plasma. Eight patients in this study had the inhibitors to vWF that were of the IgG class; the subclasses were IgG1 (7 cases) and IgG2 (1 case). Multimeric analysis of vWF showed selective loss of large multimers in most patients with AvWS similar to that of congenital type-2 von Willebrand disease (vWD). All inhibitors blocked ristocetin-mediated vWF binding to platelets. Five out of 6 IgGs evaluated here recognized the 39/34-kD fragment (residues 480/481-718) and Fragment III (residues 1-1365) that implied binding domain of glycoprotein Ib (GPIb), whereas 1 recognized Fragment I (residues 911-1365). A close relationship was found between the presence of the inhibitor and bleeding tendency. Of the 7 patients with inhibitors, 6 patients (86%) had a bleeding tendency, as well as 1 of the 15 patients without inhibitors (6%). The efficacy of treatment of underlying diseases and/or therapy with deamino D-arginine vasopressin (DDAVP) for the treatment of AvWS also depends on the presence of an inhibitor. Four of 8 patients with inhibitors (50%) had poor response to treatment of the underlying disease and/or therapy with DDAVP, as well as 1 of the 16 patients without inhibitors (6%). These results indicate that patients with AvWS developing inhibitors to vWF are likely to have bleeding problems and might be resistant to treatment of underlying diseases and/or therapy with DDAVP for bleeding to AvWS. We also showed evidence that intravenous immunoglobulin therapy (0.3 g/kg, 3 days) was effective to correct a hemostatic defect and manage severe bleeding in a patient with AvWS developing inhibitors. We might consider an additional treatment including expensive high-dose immunoglobulin therapy when uncontrollable bleeding is continued after the treatment of the underlying diseases and/or therapy with DDAVP.

Adult↗
PubMed1998

Inhibition of inducible nitric oxide synthase prevents LPS-induced acute lung injury in dogs.

Nitric oxide (NO) is produced by inducible NO synthase (iNOS) after LPS stimulation, and reacts with superoxide to form peroxynitrite. We hypothesize that in LPS-induced lung injury, NO generated by iNOS plays a key role through the formation of peroxynitrite. We developed an acute lung injury dog model by injecting LPS, and examined the effects of selective iNOS inhibitors, aminoguanidine (AG) and S-methylisothiourea sulfate (SMT), on the LPS-induced lung injury. At 24 h after LPS injection, arterial oxygen tension and mean arterial pressure decreased, and shunt ratio and lung wet-to-dry weight ratio increased. On histology, the LPS group had marked neutrophil infiltration and widening of the alveolar septa. On immunohistochemistry, iNOS and nitrotyrosine, a major product of nitration of protein by peroxynitrite, were observed in the interstitium, capillary wall, and neutrophils in the airspaces of the LPS group. Treatments with AG and SMT prevented worsening of gas exchange, hemodynamics, and wet-to-dry weight ratio. On histology, AG and SMT treatments markedly suppressed lung injury, iNOS protein, and nitrotyrosine production. We conclude that NO released by iNOS may play a critical role in the pathogenesis of LPS-induced acute lung injury. This study suggests that iNOS inhibitors may have potential in the treatment of LPS-induced acute respiratory distress syndrome.

Animals↗
PubMed1998

Comparison of the qualified occupational physician systems in the United Kingdom and Japan.

The British educational system of occupational medicine was compared to the Japanese system. Furthermore, a comparison was carried out between the certified occupational physician (COP) recognized by the Japan Society for Occupational Health in Japan and the Associateship of the Faculty of Occupational Medicine (AFOM) by the Faculty of Occupational Medicine (FOM) which is a part of the Royal College of Physicians in the United Kingdom. Judging from the comparison of the minimum total training period, the clinical training period, the occupational health training period, the method of examination and the success rate between COP and AFOM, it is suggested that the British system of occupational physicians may be better as a training system for occupational medicine and may regard occupational clinical training as more important than the Japanese system does. A comparison of a Diploma in Occupational Medicine (Dip Occ Med) approved by the FOM and the certification of occupational physicians by the Japan Medical Association has shown that the former has an examination but there is no test system in the latter. It should be discussed whether an examination system for the certification of occupational physicians should be introduced into the Japanese system in the near future.

Education, Medical, Continuing↗
PubMed1998

DNA cleavage and 8-hydroxydeoxyguanosine formation caused by tamoxifen derivatives in vitro.

DNA damage caused by tamoxifen and its derivatives was examined by estimating the conversion of supercoiled pUC18 plasmid DNA to linear form by means of agarose gel electrophoresis. N-Desmethyltamoxifen induced DNA cleavage and its effect was enhanced by the addition of reducing agents such as dithiothreitol, NADPH and 2-mercaptoethanol. 4-Hydroxytamoxifen itself had little effect, but the cleavage was slightly enhanced by the addition of reducing agents. DNA damage was higher with alpha-hydroxytoremifene than with alpha-hydroxytamoxifen, which had a prominent effect only at high concentration. The cleavage by alpha-hydroxy derivatives were not enhanced by reducing agents. No damage was induced by tamoxifen, toremifene, 3-hydroxytamoxifen or N-desmethyltoremifene. The DNA cleavage by N-desmethyltamoxifen was inhibited by the addition of EDTA, mannitol, sodium azide, methionine, catalase and superoxide dismutase. The formation of 8-hydroxy-2'-deoxyguanosine was also examined with calf thymus DNA in vitro. A slight increase of its level was found with 4-hydroxytamoxifen in the presence of dithiothreitol and also with N-desmethyltamoxifen in the presence of NADPH, but alpha-hydroxytoremifene and alpha-hydroxytamoxifen were ineffective. These experimental data suggest that among metabolites of tamoxifen, N-desmethyltamoxifen and probably also 4-hydroxytamoxifen cause oxidative DNA damage in which redox cycling is involved. The DNA damage by alpha-hydroxytoremifene appears to involve a different mechanism from that by N-desmethyltamoxifen. Tamoxifen and toremifene are possibly metabolized to the forms contributing to DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗