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Biomedical subjects

T Okubo

Publications and source records attributed to T Okubo.

At least 127 records · Page 7Linked to original sources
PubMed1998

Influenza A virus infection increases IgE production and airway responsiveness in aerosolized antigen-exposed mice.

BACKGROUND: Respiratory viral infection is known clinically to promote sensitization to antigen inhalation and the development of asthma. OBJECTIVE: The purpose of this investigation was to determine whether influenza type A virus infection enhances inhalation sensitization and increases airway responsiveness in mice. METHODS: Mice were infected by intranasal inoculation with influenza A viruses (strains: H1N1 and H3N2) or PBS. Animals were exposed to aerosols of ovalbumin on day 3. Two weeks after ovalbumin sensitization, mice were challenged with ovalbumin aerosols; 24 hours later, airway responsiveness (AR) to inhaled methacholine, levels of ovalbumin-specific IgE, and bronchoalveolar lavage fluid (BALF) were examined. RESULTS: Neither influenza A virus (H1N1 nor H3N2) alone nor ovalbumin sensitization alone caused changes in AR or IgE. However, ovalbumin sensitization after inoculation with either influenza A virus increased AR and levels of ovalbumin-specific IgE. On BALF-cell analysis, ovalbumin sensitization after inoculation with influenza virus A increased the number of lymphocytes but not the number of eosinophils. No difference in AR or IgE levels was observed between the 2 strains of influenza A viruses. Immmunostaining of BALF cells showed an increase in T cells, especially CD8(+) cells, with ovalbumin sensitization after inoculation with influenza virus A. CONCLUSION: Infection by influenza A virus enhances sensitization to inhaled antigens and airway responsiveness in mice by means of mechanisms including CD8(+) cells and antigen-specific IgE.

Acute-Phase Reaction↗
PubMed1998

Additional recognition sites in the C-terminal heparin-binding domain of fibronectin promote adhesion of PMA-treated U937 cells.

Recently we have shown an evidence that a peptide, corresponding to residues Gln1892 to Gly1910, from the C-terminal heparin-binding domain of fibronectin promotes adhesion of phorbol-12-myristate 13-acetate (PMA)-treated U937 cells and binds to both integrin alpha 4 beta 1 and glycosaminoglycans on U937 cells surface. We present additional adhesion-promoting sites to PMA-treated U937 cells present in the C-terminal heparin-binding domain of fibronectin. Three synthetic peptides (residues Ala1819 to Lys1830, designated E5; Thr1828 to Gly1940, E4; and Lys1946 to Leu1963, D1) were active to inhibit adhesion of PMA-treated U937 cells to the 29-kDa fragment comprising the C-terminal heparin-binding domain of fibronectin. Scrambled versions of these peptides had no inhibitory activity on this adhesion. The IgG-conjugated peptides (IgG-E5, IgG-E4, and IgG-D1) were also active and supported adhesion to an extent comparable to that of the 29-kDa fragment. The adhesion of PMA-treated U937 cells on these three IgG-conjugated peptides was only inhibited by glycosaminoglycans and not by integrin alpha 4 beta 1. These results indicate that additional adhesion-promoting sequences are present in the C-terminal heparin-binding domain of fibronectin and that the activity of these peptides depends on peptide sequence, mainly the result of net charges or net hydropathy indices.

Amino Acid Sequence↗
PubMed1998

Allogeneic peripheral blood progenitor cell transplantation conditioned with anti-thymocyte globulin for treatment of graft failure after allogeneic bone marrow transplantation.

A 43-year-old female with AML-M1 developed late graft failure 4 months after her first allogeneic bone marrow transplant. The patient then underwent a second transplant with peripheral blood progenitor cells obtained from the same HLA-identical brother. The donor peripheral blood progenitor cells were mobilized with granulocyte colony-stimulating factor (10 micrograms/kg daily s.c. for 6 days). The patient received horse anti-thymocyte globulin alone (15 mg/kg per day for 5 days) as the conditioning regimen. Rapid hematopoietic recovery followed a sustained engraftment. The time to reach 0.5 x 10(9)/l neutrophils and 25 x 10(9)/l platelets was 10 and 12 days, respectively. Cytogenetic analysis of bone marrow performed on day +20 demonstrated a 46XY karyotype of donor origin. There was no acute graft-versus-host disease. The patient remains in complete remission with a karnofsky score of 90% 5 months after peripheral blood progenitor cell transplantation. To treat graft failure after allogeneic bone marrow transplantation, allogeneic peripheral blood progenitor cell transplantation conditioned with anti-thymocyte globulin alone should be considered as a feasible alternative to marrow transplant.

Adult↗
PubMed1998

Human Plasma Fibronectin Mediates Adhesion of U937 Cells by RGD and CS1.

Fibronectin specifically binds to U937 cells (monocytic cell line) in a dose-dependent manner. The specific receptors for the RGD sequence have been identified as alphainfinity 5beta infinity 1wedge alpha infinity: IIb& beta infinity 3, and that for CS1 has been defined as alpha infinity 4& beta infinity 1. RGDS, CS1 peptide, and two peptides together showed similar inhibitory activities on this adhesion, while the 29-kD dispase-digested fragment of the C-terminal heparin-binding domain did not. Thus, the adhesion of fibronectin to U937 cells is mainly mediated by RGDS in the cell-binding domain and CS1 in the alternatively spliced region. Flow cytometry using monoclonal antibodies revealed expressions of alpha infinity 3& beta 1 infinity, alpha4 & beta infinity 1, and alpha infinity 5 beta 1, and not expression of alpha infinity 2 beta infinity 1. Adhesion of U937 cells to fibronectin-coated wells is specific and is inhibited by anti-alpha infinity 4 beta infinity 1 and anti- alpha infinity 5 beta infinity 1 monoclonal antibodies. The IC-50 for anti-alpha infinity 5 beta infinity 1 antibody was almost a log lower than the value for anti-alpha infinity 4 beta infinity 1 antibody. These results demonstrated that interactions of RGDS and CS1 sequence of fibronectin with alpha infinity 5 beta infinity 1 and alpha infinity 4 beta infinity 1& on U937 cells were required for the adhesion of U937 cells to fibronectin. These results may provide further information to understand the mechanism(s) of tumor cell adhesion and atherogenesis.

Journal Article↗
PubMed1998

Isolated extramedullary relapse in knee joint after allogeneic bone marrow transplantation for Ph ALL.

We report a patient who relapsed in a patella and knee joint after allogeneic bone marrow transplantation (BMT) for Ph chromosome-positive acute lymphoblastic leukemia. The patient complained of pain and swelling of knee joint 14 months post-BMT. Fluid from the knee joint included leukemic cells consistent with the immunophenotype of blasts prior to BMT and also revealed the bcr/abl transcript by reverse-transcriptase polymerase chain reaction. Magnetic resonance imaging demonstrated an abnormal signal in the patella. Radiotherapy to the localized extramedullary lesion was successful and no bone marrow relapse has been detected cytologically and cytogenetically to date. This case suggests that the physician should be aware of unusual relapse sites of leukemia post-BMT.

Adult↗
PubMed1998

Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy.

We investigated hemostatic parameters in a prospective study of 16 patients who received bone marrow transplants (BMT). We found a significant rise in the levels of fibrinogen, plasmin-alpha2 antiplasmin inhibitor complex, tissue-plasminogen activator.plasminogen activator inhibitor complex (t-PA.PAI), von Willebrand factor antigen, and thrombomodulin on day 14 after transplant compared with values before transplant. Protein C and thrombin-antithrombin III levels did not change significantly. No significant changes in prothrombin time ratio, activated partial thromboplastin time, or protein S were detected. Patients who had grades II-IV graft-versus-host disease (GVHD) (n = 6) showed a significantly higher level of t-PA.PAI on day 14 compared with those with grades 0-I GVHD (n = 10) (P = 0.0062). Three patients with grades II-IV GVHD developed thrombotic microangiopathy (TMA) on days 19, 19 and 62. In these patients, we noted significantly lower levels of fibrinogen (P = 0.0383), and significantly higher levels of t-PA.PAI (P = 0.0008) and thrombomodulin (P = 0.0001) on day 14 compared with those patients who did not develop TMA. These results suggest that prothrombotic states and endothelial damage may be caused by the conditioning regimen and/or acute GVHD during BMT; thrombomodulin values on day 14 post BMT may be useful in surveillance for TMA because of endothelial cell injury.

Adolescent↗
PubMed1998

An effective method for isolating alginate lyase-producing Bacillus sp. ATB-1015 strain and purification and characterization of the lyase.

A new alginate lyase-producing micro-organism, designated as Bacillus sp. strain ATB-1015, was effectively isolated from soil samples pretreated for 3 months with a substrate of the enzyme, sodium alginate. Alginate lyase activity was assayed by the degrading activity of biofilm of Teflon sheet discs, which was formed by a mucoid strain of Pseudomonas aeruginosa PAM3 selected from clinical isolates. The extracellular alginate lyase was precipitated with ammonium sulphate from the culture broth, and purified by gel filtration and anion exchange chromatography. The molecular weight of the lyase was estimated to be 41 kDa by SDS polyacrylamide gel electrophoresis and Sephacryl S-200 HR column chromatography. The optimum pH and temperature for the enzyme activity were around 7.5 and 37 degrees C, respectively, and the Km value was 0.17% with the substrate, sodium alginate. The lyase activity was completely inhibited by treatment with 1 mmol l-1 of EDTA and the decreased activity was almost completely recovered by the addition of 2 mmol l-1 of CaCl2. The activity was not affected by treatment with the protein denaturants, 0.01 mol l-1 of SDS or 1 mmol l-1 of urea. The lyase had substrate specificity for both the poly-guluronate and poly-mannuronate units in the alginate molecule.

Alginates↗
PubMed1998

Occupational lung diseases and global occupational health on the Net.

Occupational lung disease is a major area of concern in occupational health, exhibiting a diverse panorama across countries. While pneumoconiosis is deemed to be the most common occupational disease in many developing countries, emphasis is shifting towards asbestos-related lung diseases and occupational asthma in industrialized countries. Following the Occupational Health for All strategies set forth by the World Health Organization, we propose that a model system based upon the Global Health Network can serve as an effective vehicle towards the prevention of occupational lung diseases on a global scale. It has the potential to: (1) enhance transmission of data and collaboration with the primary health care system in disease surveillance; (2) strengthen research and information transfer and (3) promote education and training at all levels of prevention, with a possible application to the interpretation of chest radiograms.

Computer Communication Networks↗
PubMed1998

Autoantibody inhibits binding of von Willebrand factor to glycoprotein Ib and collagen in multiple myeloma: recognition sites present on the A1 loop and A3 domains of von Willebrand factor.

A 49-year-old man with multiple myeloma (IgG-lambda Bence-Jones protein positive) presented a bleeding tendency: characterized intramuscular hemorrhage. Coagulation studies showed a von Willebrand factor (vWF) defect (Duke bleeding time > 20 min; ristocetin cofactor activity [vWF:RC] < 6%; significant reduction of large multimers of vWF. Mixing study suggested the presence of inhibitor directed against vWF:RC activity and collagen binding activity of vWF. The inhibitor was identified as an antibody of the IgG class. The inhibitor blocked the interaction of vWF with glycoprotein Ib in the presence of ristocetin, as did the pepsin-digested fragment of the inhibitor [F(ab)2'], but neither blocked botrocetin-mediated interaction of vWF with glycoprotein Ib. They also inhibited the binding of vWF to immobilized collagen type I. The inhibitor and the F(ab)2' reacted strongly with native vWF and fragment I (amino acids 911-1365) and with the 39/34 kDa fragment (amino acids 480/481-718), but not with fragment II (amino acids 1366-2050) and fragment III-T2 (heavy chains, amino acids 273-511; light chains, amino acids 674-728). We conclude that the IgG antibody inhibits both vWF:RC activity and the binding of vWF to collagen by reacting with the epitopes present on the A1 loop and A3 domains of vWF.

Autoantibodies↗
PubMed1998

A new genetic variant in the Sp1 binding cis-element of cholecystokinin gene promoter region and relationship to alcoholism.

Neuropeptide cholecystokinin (CCK) and the CCK receptors in the central nervous system mediate actions on increasing firings, anxiety, and nociceptions. Furthermore, CCK modulates the release of dopamine and dopamine-related behaviors in the mesolimbic pathway. In our study, genetic variation in the promoter and coding regions of the prepro-CCK gene were analyzed among 66 Japanese, 66 American Whites, 54 Chinese, and 41 Colombian natives. Two nucleotide sequence variants were found: a frequent mutation at nucleotide position -45 C to T involved in core sequence of Sp1 binding cis-element of the promoter region, and a C to T substitution at the 1662 position in intron 2. Analysis for the segregation study in 10 families of twins confirmed codominant heredity of two alleles. Distribution of genotypes and gene frequencies of 66 controls and 108 alcoholics in Japan presented that allelic variant T type in alcoholics was found in higher frequencies than that of controls, and distribution of these genotypes was significantly different between the both groups.

Alcoholism↗
PubMed1998

Avulsion injury of cervical nerve roots: enhanced intradural nerve roots at MR imaging.

PURPOSE: To study the magnetic resonance (MR) imaging features of intradural nerve roots in avulsion injury of the cervical nerve roots. MATERIALS AND METHODS: Presurgical gadolinium-enhanced MR imaging was performed in 27 consecutive patients. The images were evaluated for enhancement of the intradural nerve roots and enhancement of the spinal cord surface at the root entry zone ("root stump" enhancement) by two radiologists, who were blinded to the clinical information. Intradural nerve roots were classified as enhanced, normal, or not visible. Root stumps were classified as enhanced or normal. The results were compared with the results of nerve root continuity studies (exploratory surgery with intraoperative recording of somatosensory evoked potentials or neurologic examination). RESULTS: At the 250 nerve levels (500 nerve roots) studied, 12 enhanced nerve roots and 42 enhanced root stumps were found. Seven enhanced nerve roots and 38 enhanced root stumps were related to preganglionic injury. Results of the kappa test for interobserver concordance on findings of intradural nerve roots and root stumps were 0.55 and 0.93, respectively. CONCLUSION: Although visualization of nerve roots is a problem, enhanced MR imaging is a noninvasive means of obtaining anatomic information and unique physiologic information on injured intradural nerve roots.

Adolescent↗
PubMed1998

Nitric oxide modulates cardiac contractility and oxygen consumption without changing contractile efficiency.

Nitric oxide (NO) affects myocardial contractility and myocardial oxygen consumption (MVO2) in vitro. In alpha-chloralose-anesthetized dogs instrumented for the measurements of left ventricular (LV) pressure, LV volume using a conductance catheter, coronary blood flow, and coronary venous oxygen saturation (ScvO2) using a fiber-optic catheter, LV end-systolic pressure-volume relationships (ESPVR) and the relationship between MVO2 and LV pressure-volume area (PVA) were analyzed before and after intravenous infusions of the NO synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA; 5 mg/kg, 8 dogs) and the NO substrate L-arginine (600 mg/kg, 7 dogs). L-NMMA increased the slope of the ESPVR (Emax) (P < 0.05) without changing contractile efficiency indicated by the inverse of the slope of the MVO2-PVA line. L-NMMA also increased unloaded MVO2, indicated by the y-axis intercept of the MVO2-PVA line (P < 0.05). In contrast, L-arginine decreased Emax (P < 0.05) while decreasing MVO2 (P < 0.05), and without changing contractile efficiency. The basal oxygen metabolism was not affected by L-NMMA and L-arginine. These data imply that endogenous NO spares MVO2 by reducing oxygen use in excitation-contraction coupling and attenuates cardiac contractility without changing contractile efficiency.

Animals↗
PubMed1998

Neuropeptides mediate the ozone-induced increase in the permeability of the tracheal mucosa in guinea pigs.

We examined the effects of acute exposure to ozone on the permeability of the tracheal mucosa and the contribution of neural pathways to the effects of ozone using horseradish peroxidase (HRP; mol wt 40,000) as a marker of lumen-to-blood transfer of a macromolecule in guinea pigs in vivo. Each guinea pig was anesthetized and exposed for 30 min to either ozone [0.5 or 3 parts/million (ppm)] or air. Immediately after exposure, a tracheal segment was isolated between two polyethylene cannulas in vivo and filled with HRP solution (50 mg/ml). Blood samples were drawn before and 10, 20, 30, and 40 min after the intratracheal instillation of HRP. The plasma levels of HRP in guinea pigs exposed for 30 min to 3 ppm of ozone, but not to 0.5 ppm of ozone, were significantly greater than those in guinea pigs exposed to air. Although the increased plasma HRP levels after exposure to 3 ppm of ozone were unaffected by propranolol or atropine, they were completely inhibited by pretreatment with capsaicin (50 mg/kg sc, injected in two doses). These results suggest that endogenous neuropeptides mediate the ozone-induced increase in the permeability of the tracheal mucosa in guinea pigs in vivo, but neither an adrenergic nor a cholinergic pathway appears to be involved.

Animals↗
PubMed1998

Cardiac sympathetic stimulation increases cardiac contractility but decreases contractile efficiency in canine hearts in vivo.

The effect of cardiac sympathetic stimulation on cardiac contractile efficiency was studied in dogs. In 19 anesthetized and open-chest dogs, left ventricular (LV) pressure, LV volume, coronary blood flow and coronary venous oxygen saturation were measured simultaneously. The LV end-systolic pressure volume relations (ESPVR) and the relation between myocardial oxygen consumption (VO2)-pressure volume area (PVA) were obtained during a transient occlusion of the inferior vena cava before and after sympathetic stimulation (9V, 6 Hz, 40 sec) both with and without 50 mg/kg of 2,3-butanedione monoxime (BDM). Without BDM, sympathetic stimulation increased the slope of ESPVR by 62% (p<0.05), the slope of the VO2-PVA line by 19% (p<0.05) and the y-axis intercept of the VO2-PVA by 65% (p<0.05). With BDM, the increase in the slope of the VO2-PVA line became insignificant although other responses were similarly preserved. These data imply that cardiac sympathetic stimulation decreases cardiac contractile efficiency through mechanisms by which norepinephrine-induced beta-adrenergic activation enhances myosin ATPase-operating ATP hydrolysis in crossbridge formation.

Animals↗
PubMed1998

[A survey on return to work and fitness for work in Japan: the systems provided in corporate regulations and their application].

We conducted a survey to evaluate the current situation and the application of systems for return to work (RTW) and fitness for work (FFW) in Japanese companies. Self-administered questionnaires were mailed to 351 occupational health (OH) physicians listed in the membership directory of the Japan Society for Occupational Health published in 1990. The item of information sought were the size and industrial type of the company, the organization of OH staff, the process of assessment of RTW, the provision for sick leave in corporate regulations, the FFW criteria, and job training systems for RTW. Of the 145 companies from which questionnaire replies were received from OH physicians (response rate: 41%), 123 (85%) were manufacturing industries. When classified according to the number of employees, 41 (28%) had 3000 or more, 66 (46%) had between 1000 and 2999, 26 (18%) had 999 or fewer and 12 (8%) were unknown. 144 companies (99%) had provisions on temporary retirement in their corporate regulations. As for who makes compensation during temporary retirement, 66 (48%) and 61 (44%) companies answered "both company and health insurance society" and "health insurance society alone," respectively. 136 companies (94%) carried out assessment of RTW, and involved OH professionals and other related staff in the process of assessment. In the majority of cases, the OH physicians were in charge of the decision-making process on RTW and were authorized to make the final decision. In the companies with 3000 or more employees, the cases of longer-term sick leave were assessed in a more complete process than those of shorter-term sick leave. 119 companies (88%) conducted on additional health examination to assess the employee's FFW. Sixty-four companies (47%) had standardized criteria on FFW. One hundred and eighteen companies (83%) had job training systems for employees' RTW, and they mainly introduced restricting one's job and/or reducing one's work-load. It was suggested that complete systems for RTW and FFW were more available among companies with 3000 or more employees than among companies with 2999 or fewer employees.

Data Collection↗
PubMed1998

Serum level of eosinophil cationic protein in patients with chronic cough: relationship to blood eosinophils and airway hyperresponsiveness.

We measured the serum level of eosinophil cationic protein (ECP), determined the blood eosinophil count, and assessed pulmonary function by spirometry and airway responsiveness to methacholine in 80 patients with a cough lasting longer than 3 weeks without an obvious cause. The serum level of ECP was above the cutoff value of 15.7 ng/mL (mean + 2 SD in 105 healthy control adults) in 30 (37.5%) of 80 patients (high-serum-ECP group). The blood eosinophil count was significantly higher in the high-serum-ECP group than in the normal-serum-ECP group (p < 0.01). The cumulative dose of methacholine causing a 35% decrease in respiratory conductance (PD35Grs) was significantly lower in the high-serum-ECP group than in the normal-serum-ECP group (p < 0.001). The serum concentration of ECP was correlated with the blood eosinophil count and the PD35Grs (r = 0.59, p < 0.001 and r = -0.48, p < 0.001, respectively). These findings suggest a possible role for serum level of ECP in management of patients with chronic cough.

Adult↗