Tokaimura accident. Neutron dose estimates from 5-yen coins.
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Japan↗
Biomedical subjects
M Kohno
Publications and source records attributed to M Kohno.
Dopamine as a novel antioxidative agent for rat vascular smooth muscle cells through dopamine D(1)-like receptors.
BACKGROUND: To elucidate the roles of vascular D(1)-like receptors in atherosclerosis, the effects of the specific D(1)-like agonists on platelet-derived growth factor (PDGF)-BB-mediated oxidative stress in vascular smooth muscle cells (VSMCs) were studied. METHODS AND RESULTS: Immunohistochemical studies demonstrated the coexistence of D(1A) and D(1B) dopamine receptors in VSMCs. Western blotting revealed a band of approximately 70 kDa for D(1A) and D(1B) dopamine receptors. VSMCs stimulated by PDGF-BB exhibited increased oxidative stress directly measured by flow cytometry. These effects were prevented by dopamine, SKF 38393, or YM 435, and this prevention was reversed by Sch 23390. These effects were blocked by a specific protein kinase A (PKA) inhibitor, N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide (H 89). The PDGF-BB-mediated increase in oxidative stress of VSMCs was significantly suppressed by the indirect phospholipase D (PLD) inhibitor suramin or the specific protein kinase C (PKC) inhibitor calphostin C. Both antisense but neither sense nor scrambled oligonucleotides to D(1A) and D(1B) receptors inhibited dopamine-induced suppression of increase in oxidative stress of VSMCs induced by PDGF-BB. CONCLUSIONS: These findings suggest that vascular D(1)-like receptors (D(1A) and D(1B) receptors) inhibit any increase in oxidative stress of VSMCs, possibly through activation of PKA and suppression of PLD and PKC.
Animals↗
G(i1) and G(oA) differentially determine kinetic efficacies of agonists for kappa-opioid receptor.
We examined the diversity of single receptor function by measuring receptor-G protein coupling in the baculovirus-Sf21 expression system. In comparative studies using Sf21 cell membranes expressing kappa-opioid receptor (KOR) plus Galpha(i1)beta(1)gamma(2) or KOR plus Galpha(oA)beta(1)gamma(2), there was no significant difference between both preparations in the K(i) values of various kappa-opioid ligands for the displacement of [(3)H]U69593 binding. However, a marked difference in the rank order of agonists to stimulate [(35)S]GTPgammaS binding was observed between both preparations. These findings suggest that agonist efficacy is dependent on the population of different G proteins expressed in various tissues.
Animals↗
Preferential inhibition of cyclooxygenase-2 by meloxicam in human rheumatoid synoviocytes.
The aim of this study was to evaluate the anti-inflammatory effect of 4-hydroxy-2-methyl-N-[5-methyl-2-thiazolyl]-2H-1, 2-benzothiazine-3-carboxamide-1,1-dioxide (meloxicam) using cultured rheumatoid synovial fibroblast-like cells (synoviocytes). Synoviocytes were treated with meloxicam in the presence or absence of interleukin-1beta. Meloxicam had no effect on both cyclooxygenase-1 and -2 expression as determined by Western blot analysis, immunohistochemical staining, and reverse transcription polymerase chain reaction (RT-PCR). Even the lower doses of meloxicam inhibited cyclooxygenase-2 activity, but only the higher doses of meloxicam inhibited cyclooxygenase-1 activity as determined by prostaglandin E(2) synthesis assay. So meloxicam had a preferential inhibitory effect of cyclooxygenase-2 relative to cyclooxygenase-1 on cultured rheumatoid synoviocytes without affecting cyclooxygenase expression. On the other hand, indomethacin had no selectivity and dexamethasone inhibited the expression of cyclooxygenase-2. Our data indicate that clinical efficacy and safety of meloxicam for rheumatoid arthritis may result from its preferential inhibition of cyclooxygenase-2 activity relative to cyclooxygenase-1 on rheumatoid synoviocytes.
Anti-Inflammatory Agents↗
Inhibition of human lung cancer cell growth by the peroxisome proliferator-activated receptor-gamma agonists through induction of apoptosis.
Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptors superfamily, have an important regulatory role in adipogenesis and inflammation. PPAR-gamma ligands induce terminal differentiation and growth inhibition of human breast cancer cells and prostatic cancer cells. In this study, we demonstrated that PPAR-gamma, but not PPAR-alpha, was expressed in human lung cancer cell lines by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. We also found that the synthetic PPAR-gamma agonist thiazolidinedione compounds (troglitazone) and the endogenous PPAR-gamma ligand, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), inhibited the growth of human lung cancer cells through the induction of apoptosis. However, PPAR-alpha agonist (bezafibrate) and other prostanoids (PGE(2), PGF(2alpha)) did not induce apoptosis. These findings suggest that PPAR-gamma may play an important role in the pathogenesis of lung cancer and that PPAR-gamma agonist may be useful therapeutic agents in the treatment of human lung cancer.
Apoptosis↗
Selective inhibition of cyclooxygenase-2 with antisense oligodeoxynucleotide restricts induction of rat adjuvant-induced arthritis.
The effects of cyclooxygenase (COX)-2 antisense oligodeoxynucleotide (ODN) in induction of adjuvant-induced arthritis were investigated. Female Lewis rats were injected with Mycobacterium butyricum intradermally at the base of tails to induce arthritis. Synthetic 18 mer phosphorothioate ODNs corresponding to the translation initiation site of rat COX-2 mRNA were prepared. The antisense (AS), sense (S), and "scrambled" (Sc) ODNs were intraperitoneally administered. Arthropathy was evaluated with arthritis score, paw edema, and histological examination. Expression of COX-1 and -2 protein and mRNA were examined with immunostaining and reverse-transcription polymerase chain reaction, respectively. COX-2 AS ODN significantly suppressed induction of arthritis in a dose-dependent manner without severe adverse effects, whereas S and Sc ODNs did not show significant inhibitory effects. COX-2 mRNA and protein expression were also suppressed only by COX-2 AS ODN without any alteration of COX-1 expression. These data suggest that selective inhibition of COX-2 with AS ODN may have a therapeutic potency in the treatment of rheumatoid arthritis.
Animals↗
Human interferon-alpha induces immobility in the mouse forced swimming test: involvement of the opioid system.
In a previous study, we indicated that human interferon (IFN)-alpha (IFN-alpha, 6 x 10(4) IU/kg, i.v.), but not human IFN-beta or -gamma, prolonged the immobility time of the forced swimming test in mice. In this study, we investigated the mechanism of the effect of human IFN-alpha. None of the mouse IFNs tested (IFN-alpha/beta, IFN-beta, and IFN-gamma, 3 x 10(5) U/kg, i.v.) changed the immobility time or the spontaneous locomotor activity in mice. Indomethacin (10 mg/kg, s.c.), a cyclooxygenase inhibitor, did not affect the increase in the immobility time induced by human IFN-alpha (6 x 10(4) IU/kg, i.v.). However, naloxone (1 mg/kg, s.c.), an opioid receptor antagonist, blocked the increasing caused by human IFN-alpha in the forced swimming test. These results suggest that the increase in the immobility time caused by human IFN-alpha in the forced swimming test might be mediated through opioid receptors, but not mouse IFN receptors.
Animals↗
Superconductivity from flat dispersion designed in doped mott insulators
Routes to enhance superconducting instability are explored for doped Mott insulators. With the help of insight for criticalities of metal-insulator transitions, geometrical design of lattice structure is proposed to control the instability. A guideline is to explicitly make flat band dispersions near the Fermi level without suppressing two-particle channels. In a one-dimensional model, numerical studies show that our prescription with finite-ranged hoppings realizes large enhancement of spin-gap and pairing dominant regions. We also propose several multiband systems, where the pairing is driven by intersite Coulomb repulsion.
Journal Article↗
Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells.
Adult T-cell leukemia (ATL) is characterized by infiltration of various tissues by circulating ATL cells, a finding often associated with a poor prognosis. Leukocyte migration from the circulation into tissues depends on integrin-mediated adhesion to the endothelium, and integrins are tightly regulated by several factors, such as chemokines. In this study, we focused on the interaction between chemokines and chemokine receptors on ATL cells to understand factors involved in ATL cell infiltration of lymphoid organs. We compared freshly isolated ATL cells from patients with and without lymphoid organ involvement for the expression of the chemokine receptor CCR7/EBI1, the functional receptor for secondary lymphoid-tissue chemokine (SLC), which is expressed at high levels by high endothelial venules of lymph nodes and Peyer's patches. Reverse transcriptase-polymerase chain reaction and flow cytometric analysis, using anti-CCR7 monoclonal antibody (CCR7.6B3), revealed that ATL cells from patients with lymphoid organ involvement expressed significantly more CCR7/EBI1 than control CD4(+)CD45RO(+) T cells and ATL cells from patients without lymphoid organ involvement. Consequently, significantly more ATL cells from patients with lymphoid organ involvement than control CD4(+)CD45RO(+) T cells and ATL cells from patients without lymphoid organ involvement adhered to surfaces coated with ICAM-1 and SLC or EBI1-ligand chemokine (ELC), another ligand for CCR7/EBI1, under static and flow conditions and migrated toward SLC or ELC at a low concentration (30 ng/ml). These findings suggest that increased CCR7/EBI1 expression plays a role in lymphoid organ infiltration of ATL cells. (Blood. 2000; 30-38)
Adult↗
Splenomegaly and chronic disseminated intravascular coagulation in Osler-Weber-Rendu disease: a case report.
A 45-year-old Japanese woman with splenomegaly and thrombocytopenia was referred to our hospital. The diagnosis of Osler-Weber-Rendu disease (Osler's disease) was made because of spotty telangiectasia on her tongue, recurrent epistaxis since childhood, and a diathesis indicated by her family history. The patient's laboratory examination revealed anemia, thrombocytopenia, and other data consistent with chronic disseminated intravascular coagulation (DIC). Bone marrow examination was normal. Abdominal computed tomography showed marked enlargement of the spleen with deformity and calcified plaque, not homogeneously enhancing. Hypersplenism was not observed. Platelet scintigraphy indicated a remarkable uptake in the spleen. She was diagnosed as having chronic DIC associated with vascular lesions of Osler's disease in the spleen. Splenectomy was performed and the subsequent pathological findings indicated that fragility of the fine vascular architecture of the splenic red pulp might have been responsible for pathogenesis. The large pooling of blood with coagulation was thought to be secondary.
Disseminated Intravascular Coagulation↗
A novel color M-mode Doppler echocardiographic index for left ventricular relaxation: depth of the maximal velocity point of left ventricular inflow in early diastole.
Color M-mode Doppler echocardiography (CMD) has been utilized in assessing left ventricular (LV) filling dynamics. We tested a novel CMD index, the depth of the spatiotemporal maximum of early diastolic inflow (D-maxV) in the left ventricle, to clarify its significance in assessing LV diastolic function. In 26 normal subjects and 32 patients with ischemic heart disease, D-maxV was determined with CMD as the distance from the mitral valve opening point to the center of the aliasing area in early diastole. Transmitral flow velocity was measured with pulsed Doppler. During routine catheterization, high-fidelity LV pressure measurements yielded diastolic variables in patients. D-maxV was significantly lower in the patients than the normals (13.0+/-7.0 vs 23.4+/-6.8 mm, P < 0.0001). D-maxV exhibited significant linear correlations with the minimal first derivative of LV pressure (r = 0.72, P < 0.01), the time constant of isovolumic relaxation (r = -0.67, P < 0.01), and LV minimal pressure (r = -0.53, P < 0.02) in the patients with wide ranges of peak early to late inflow velocity ratio (0.43-3.9) and deceleration time of early filling (79-293 ms). D-maxV showed an inverse correlation with LV end-diastolic pressure (r = -0.53, P < 0.02) and no significant correlation with mean pulmonary capillary wedge pressure. Moreover, Kaplan-Meier analysis focusing on the patients with myocardial infarction revealed that the group with D-maxV < 10.4 mm (n = 13) exhibited a lower cumulative cardiac event-free rate than that with D-maxV > or = 10.4mm (n = 14) (49.4% vs 92.9% at 5 years, P < 0.05). The depth of the spatiotemporal maximum of early diastolic LV inflow velocity reflects LV relaxation and is free of pseudonormalization. Evaluation of the LV relaxation separately from preload may have a prognostic value for myocardial infarction.
Adult↗
Altered interaction of FKBP12.6 with ryanodine receptor as a cause of abnormal Ca(2+) release in heart failure.
OBJECTIVE: Little information is available as to the Ca(2+) release function of the sarcoplasmic reticulum (SR) in heart failure. We assessed whether the alteration in this function in heart failure is related to a change in the role of FK binding protein (FKBP), which is tightly coupled with the cardiac ryanodine receptor (RyR) and recently identified as a modulatory protein acting to stabilize the gating function of RyR. METHODS: SR vesicles were isolated from dog LV muscles [normal (N), n=6; heart failure induced by 3-weeks pacing (HF), n=6]. The time course of the SR Ca(2+) release was continuously monitored using a stopped-flow apparatus, and [3H]ryanodine-binding and [3H]dihydro-FK506-binding assays were also performed. RESULTS: FK506, which specifically binds to FKBP12.6 and dissociates it from RyR, decreased the polylysine-induced enhancement of [3H]ryanodine-binding by 38% in N (P<0.05) but it had no effect in HF. In HF, the rate constant for the polylysine-induced Ca(2+) release from the SR was 61% smaller than in N. FK506 decreased the rate constant for the polylysine-induced Ca(2+) release by 67% in N (P<0.05) but had no effect in HF. The [3H]dihydro-FK506-binding assay revealed that the number (B(max)) of FKBPs was decreased by 83% in HF (P<0.05), while the K(d) value was unchanged. FK506 did not significantly change SR Ca(2+.)-ATPase activity in either N or HF. CONCLUSIONS: In HF, the number of FKBPs showed a tremendous decrease; this may underlie the RyR-channel instability and the impairment of the Ca(2+) release function of RyR seen in the failing heart.
Analysis of Variance↗
Suppression by eicosapentaenoic acid of oxidized low-density lipoprotein and lysophosphatidylcholine-induced migration in cultured rat vascular smooth muscle cells.
The migration of medial smooth muscle cells into the intima is proposed to be an initial process of intimal thickening in atherosclerotic lesions. The present study was designed to determine whether pretreatment with the antiatherogenic agent eicosapentaenoic acid (EPA) inhibits the migration induced by oxidized low-density lipoprotein (LDL) and its major phospholipid component, lysophosphatidylcholine (lyso-PC), in cultured rat vascular smooth muscle cells (VSMCs) using Boyden's chamber method. The effects of EPA pretreatment on angiotensin II (Ang II)- and platelet-derived growth factor BB (PDGF BB)-induced migration were also examined in these cells. Oxidized LDL and lyso-PC induced migration in a concentration-dependent manner. EPA pretreatment clearly suppressed oxidized LDL (200 microg/mL)- and lyso-PC (10(-5) mol/L)-induced migration between 40 and 160 micromol/L. EPA pretreatment also suppressed Ang 11 (10(-7) mol/L)- and PDGF BB (5 ng/mL)-induced migration at a concentration of 80 and 160 micromol/L. However, in a trypan blue exclusion test, dead cells stained with trypan blue were not found 24 hours after treatment with EPA. These results suggest that EPA suppresses VSMC migration induced by oxidized LDL and lyso-PC, as well as Ang II and PDGF BB. These preliminary data concerning the effects of EPA may partly explain the antiatherosclerotic effects of this agent.
Animals↗
Physical properties of the mitral valve tissue assessed by tissue sound speed in cardiac amyloidosis: relationship to the severity of mitral regurgitation.
Cardiac amyloidosis has been documented to show mitral regurgitation (MR) and a thickened mitral valve (MV) due to amyloid deposits. However, the changes in the physical properties of the thickened MV tissue in cardiac amyloidosis, which may be a causative factor of the MR, have not been described. Physical properties of the tissue, which are expressed by the elastic bulk modulus, can be evaluated by tissue sound speed. If biological tissue is assumed to be fluid-like, the tissue sound speed may be given by c= square root of K/rho, where c is the tissue sound speed, K is the elastic bulk modulus, and rho is the density. A reduction in tissue sound speed indicates a reduction in the elastic bulk modulus of the tissue, assuming that there is little change in rho. This suggests that the tissue is less elastic. The purpose of this study was to assess the physical properties of MV tissue by evaluating the sound speed of the MV tissue in cardiac amyloidosis. MV specimens were obtained at autopsy from 20 control adults without cardiovascular diseases and from 20 patients with cardiac amyloidosis. An acoustic microscope operating at 450 MHz was used to measure the tissue sound speed in the tip and basal portions of the MV tissue. The density of MV tissue was measured by microgravimetry. The severity of the MR had been evaluated by Doppler echocardiography before death, and it was compared with the tissue sound speed measured after death. In cardiac amyloidosis showing mild MR, the tissue sound speed of the MV in the tip portion (1605 +/- 19 m/s) and in the basal portion (1791 +/- 64 m/s) were lower than the corresponding values in control subjects (1637 +/- 42 m/s and 1851 +/- 62 m/s). However, these differences were not statistically significant. In cardiac amyloidosis showing moderate MR, the tissue sound speed of MV in the tip portion (1563 +/- 17 m/s) and in the basal portion (1654 +/- 59 m/s) were significantly lower than the corresponding values in the control subjects (p < 0.001) and the patients with mild MR (p < 0.05). No significant differences were observed in the density of MV tissue among the three groups. Therefore, the low value of the MV tissue sound speed in patients with cardiac amyloidosis indicated a reduced elastic bulk modulus, suggesting the less elasticity of the MV tissue. Furthermore, the patients with moderate MR demonstrated the greater reduction in the tissue sound speed than the patients with mild MR. The data suggest that the changes in physical properties of the MV tissue may be one of the causes of MR in cardiac amyloidosis.
Acoustics↗
Effect of static magnetic fields on bacteria: Streptococcus mutans, Staphylococcus aureus, and Escherichia coli.
Biological effect of static magnetic field was investigated by using ferrite magnets to conduct a magnetic field exposure experiment on three species of bacteria: Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The effects were evaluated by culturing the bacteria and determining their growth rate, the maximum numbers of bacteria, and [3H]-thymidine incorporation. The results showed that the ferrite magnet caused strength-dependent decreases in the growth rate and growth maximum number of bacteria for S. mutans and S. aureus when cultured under anaerobic conditions, but that their growth was not inhibited under aerobic conditions. In addition, [3H]-thymidine was added after culturing each of the species of bacteria for 18 h. After that, culture was continued until 24 h, and changes in [3H]-thymidine incorporation were investigated. But no effect of the magnetic fields was detected. These findings suggested that oxygen related to growth the cases of S. mutans, S. aureus. However, no growth effects were detected on E. coli cultures.
Journal Article↗
Characteristics of polyarthritis in rabbits by hyperimmunization with attenuated Enterococcus faecalis.
To produce polyarthritis and rheumatoid factor like substance (RFLS), rabbits were hyperimmunized intravenously with 0.02% thimelosal (TMS)-treated Enterococcus faecalis (E. faecalis) as a persistent bacterial flora. Swelling of knee joints occurred at a rate of 41% (27/66), and of shoulder joints at a rate of 25% (17/66) while that of elbow joints occurred at a rate of 4.5% (3/66). On culturing of knee joint fluids, no colonies appeared while 2/4 fluid specimens from the shoulder joints gave positive colonies for 78 days after the first immunization; thereafter, no colonies appeared. On histological examination, in early stages, acute inflammatory reactions with degenerative changes of synovial tissue was observed. In later stages, chronic inflammatory changes, proliferation of synovial cells with pannus formation, destruction of articular cartilage and subchondral bone were observed. RFLS titer showed bi-phasic peaks at 11 days and 41 days after the first immunization. A high incidence of polyarthritis, particularly knee joints, occurred. Thus, hyperimmunization with attenuated E. faecalis as a normal intestinal flora may provide an animal model of chronic polyarthritis.
Agglutinins↗
Patterns and mechanisms of pedestrian injuries induced by vehicles with flat-front shape.
To clarify the difference between flat-front vehicles and bonnet-front vehicles with regard to the patterns and mechanisms of vehicle-induced pedestrian injuries, we investigated 101 cases of pedestrians who were struck by the front of a vehicle. There were 33 flat-front vehicle collision cases and 68 bonnet-front vehicle collision cases. The frequency of chest injuries in flat-front vehicle collisions (30.3%) was significantly higher than that in bonnet-front vehicle collisions (11.8%). Lower leg fractures were more common in bonnet-front vehicle collisions than in flat-front vehicle collisions. Although head injuries were common in both cases, the mechanisms of these injuries differed. The pedestrians who were struck by flat-front vehicles tended to sustain more severe injuries at lower impact speeds. All of these results stem from the difference in the front shape of the two types of vehicle. Pedestrians who are struck by the front of flat-front vehicles receive the impact force to the trunk, particularly the chest, at the initial impact and are thrown out forward after the impact, because the front of these vehicles is perpendicular to the road.
Journal Article↗
Fatal cardiovascular injuries to the unbelted occupant associated with airbag deployment: two case-reports.
We present two forensic autopsy cases of unbelted occupants associated with the airbag deployment in motor vehicle collisions. Both victims suffered from cardiovascular injuries which were the cause of death. Case 1: A 50-year-old man sustained a contusion on the left anterior chest with rib fractures and laceration of the intrapericardial inferior vena cava, the right ventricle, and the right pleuropericardium. Case 2: A 40-year-old man sustained multiple rib fractures, sternal fracture, and the rupture of the right ventricle. Autopsies and vehicle examinations revealed that both victims' chest seemed to strike the steering wheel through the deployed airbag. Therefore, we determined that the source of blunt impact force is the steering wheel through the airbag rather than airbag deployment only. In light of these two cases, we learned that the steering wheel should be considered as the blunt impact force inducing cardiovascular injuries even in cases in which the airbag has been deployed.
Journal Article↗