Adverse effects of methylprednisolone pulse therapy in refractory Kawasaki disease.
Explore the source record for details and available documents.
Anticoagulants↗
Biomedical subjects
M Miura
Publications and source records attributed to M Miura.
Recovery of stem cells from cryopreserved periodontal ligament.
Human post-natal stem cells possess a great potential to be utilized in stem-cell-mediated clinical therapies and tissue engineering. It is not known whether cryopreserved human tissues contain functional post-natal stem cells. In this study, we utilized human periodontal ligament to test the hypothesis that cryopreserved human periodontal ligament contains retrievable post-natal stem cells. These cryopreserved periodontal ligament stem cells maintained normal periodontal ligament stem cell characteristics, including expression of the mesenchymal stem cell surface molecule STRO-1, single-colony-strain generation, multipotential differentiation, cementum/periodontal-ligament-like tissue regeneration, and a normal diploid karyotype. Collectively, this study provides valuable evidence demonstrating a practical approach to the preservation of solid-frozen human tissues for subsequent post-natal stem cell isolation and tissue regeneration. The present study demonstrates that human post-natal stem cells can be recovered from cryopreserved human periodontal ligament, thereby providing a practical clinical approach for the utilization of frozen tissues for stem cell isolation.
Adult↗
The first record of Dirofilaria immitis infection in a Humboldt penguin, Spheniscus humboldti.
Dirofilaria immitis infection is an important parastic disease in many mammals, especially canids, but has not been reported in bird hosts. Filarial worms were isolated from the lumen of the right atrium of the heart and the connective tissue of the lung of a captive female Humboldt penguin, Spheniscus humboldti, that died at a zoo in Japan. One of these worms was observed morphologically and identified as D. immitis by features such as 4 pairs of cephalic papillae, 1 pair of cervical papillae, esophagus divided into 2 regions, 4 pairs of pre-anal papillae, 5 pairs of post-anal papillae, and unequal spicules. In addition, the partial DNA sequence (234 bp) of mitochondrial CO / gene of the filarial worm was identical to that of D. immitis. This is the first report of D. immitis infection in a bird.
Animals↗
Porphyrin-mediated boron neutron capture therapy: a preclinical evaluation of the response of the oral mucosa.
Preclinical studies are in progress to determine the potential of boron neutron capture therapy (BNCT) for the treatment of carcinomas of the head and neck. Recently, it has been demonstrated that various boronated porphyrins can target a variety of tumor types. Of the porphyrins evaluated so far, copper tetracarboranylphenyl porphyrin (CuTCPH) is potentially a strong candidate for clinical use. In the present investigation, the response of the oral mucosa to CuTCPH-mediated boron neutron capture (BNC) irradiation was assessed using the ventral surface of the tongue of adult male Fischer 344 rats, a standard rodent model. CuTCPH was administered by intravenous infusion, at a dose of 200 mg/kg body weight, over a 48-h period. Three days after the end of the administration of CuTCPH, biodistribution studies indicated very low levels of boron (<2 microg/g) in the blood. Levels of boron in tongue tissue were 39.0 +/- 3.8 microg/g at this time. This was the time selected for irradiation with single doses of thermal neutrons from the Brookhaven Medical Research Reactor. The estimated level of boron-10 in the oral mucosa was used in the calculation of the physical radiation doses from the 10B(n,alpha)7Li reaction. This differs from the approach using the present generation of clinical boron carriers, where boron levels in blood at the time of irradiation are used for this calculation. Dose-response curves for the incidence of mucosal ulceration were fitted using probit analysis, and the doses required to produce a 50% incidence of the effect (ED50 +/- SE) were calculated. Analysis of the dose-effect data for CuTCPH-mediated BNC irradiation, compared with those for X rays and thermal neutrons alone, gave a compound biological effectiveness (CBE) factor of approximately 0.04. This very low CBE factor would suggest that there was relatively low accumulation of boron in the key target epithelial stem cells of the oral mucosa. As a consequence, with low levels of boron (<2 microg/g) in the blood, the response of the oral mucosa to CuTCPH-mediated BNCT will be governed primarily by the radiation effects of the thermal neutron beam and not from the boron neutron capture reaction [10B(n,alpha)7Li].
Animals↗
Pharmacokinetic differences between the enantiomers of lansoprazole and its metabolite, 5-hydroxylansoprazole, in relation to CYP2C19 genotypes.
OBJECTIVE: The purpose of this study was to elucidate the pharmacokinetics of each enantiomer of lansoprazole and 5-hydroxylansoprazole in three different CYP2C19 genotype groups of Japanese subjects. METHODS: Healthy subjects ( n=18), of whom 6 were homozygous extensive metabolizers (homEMs), 6 were heterozygous extensive metabolizers (hetEMs) and 6 were poor metabolizers (PMs), participated in the study. After a single oral dose of 60 mg of racemic lansoprazole, the plasma concentrations of the lansoprazole enantiomers, 5-hydroxylansoprazole enantiomers and lansoprazole sulfone were measured for 24 h post-dose. RESULTS: The plasma concentrations of ( R)-lansoprazole were remarkably higher in all three CYP2C19 genotype groups than those of the corresponding ( S)-enantiomer. The mean maximum plasma concentration ( C(max)) of ( S)-lansoprazole differed significantly among the three groups, whereas there was no difference for the ( R)-enantiomer. The relative area under the plasma concentration (AUC) ratios of ( R)- and ( S)-lansoprazole in the homEMs, hetEMs, and PMs were 1:1.5:4.0 and 1:1.8:7.4, respectively. Yet, the relative AUC ratios of 5-hydroxylansoprazole to lansoprazole for the ( R)- and ( S)-enantiomers in the homEMs, hetEMs, and PMs were almost the same (1:0.73:0.12 and 1:0.77:0.13, respectively). However, the AUC ratios of the ( S)-enantiomer were 13-fold greater for the three CYP2C19 genotypes than those of the corresponding ( R)-enantiomer. CONCLUSIONS: The magnitude of the contribution of CYP2C19 to the 5-hydroxylation of ( S)-lansoprazole was greater than that of the ( R)-enantiomer. The R/S ratios for the AUC of lansoprazole for the homEMs, hetEMs and PMs were 12.7, 8.5 and 5.8, respectively, suggesting a significant effect of CYP2C19 polymorphisms on the stereoselective disposition of lansoprazole.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Evidence for an oscillatory signature in atmospheric neutrino oscillations.
Muon neutrino disappearance probability as a function of neutrino flight length L over neutrino energy E was studied. A dip in the L/E distribution was observed in the data, as predicted from the sinusoidal flavor transition probability of neutrino oscillation. The observed L/E distribution constrained nu(micro)<-->nu(tau) neutrino oscillation parameters; 1.9x10(-3) 0.90 at 90% confidence level.
Journal Article↗
Search for electron neutrino appearance in a 250 km long-baseline experiment.
We present a search for electron neutrino appearance from accelerator-produced muon neutrinos in the K2K long-baseline neutrino experiment. One candidate event is found in the data corresponding to an exposure of 4.8 x 10(19) protons on target. The expected background in the absence of neutrino oscillations is estimated to be 2.4+/-0.6 events and is dominated by misidentification of events from neutral current pi(0) production. We exclude the nu(micro) to nu(e) oscillations at 90% C.L. for the effective mixing angle in the 2-flavor approximation of sin((2)2theta(microe)( approximately 1/2sin((2)2theta(13))>0.15 at Deltam(2)(microe)=2.8 x 10(-3) eV(2), the best-fit value of the nu(micro) disappearance analysis in K2K. The most stringent limit of sin((2)2theta(microe)<0.09 is obtained at Deltam(2)(microe)=6 x 10(-3) eV(2).
Journal Article↗
Limits on the neutrino magnetic moment using 1496 days of Super-Kamiokande-I solar neutrino data.
A search for a nonzero neutrino magnetic moment has been conducted using 1496 live days of solar neutrino data from Super-Kamiokande-I. Specifically, we searched for distortions to the energy spectrum of recoil electrons arising from magnetic scattering due to a nonzero neutrino magnetic moment. In the absence of a clear signal, we found micro(nu)</=(3.6x10(-10))micro(B) at 90% C.L. by fitting to the Super-Kamiokande day-night spectra. The fitting took into account the effect of neutrino oscillation on the shapes of energy spectra. With additional information from other solar neutrino and KamLAND experiments constraining the oscillation region, a limit of micro(nu)</=(1.1x10(-10))micro(B) at 90% C.L. was obtained.
Journal Article↗
Anomalously hindered E2 strength B(E2;2+(1)-->0+) in 16C.
The electric quadrupole transition from the first 2(+) state to the ground 0(+) state in 16C is studied through measurement of the lifetime by a recoil shadow method applied to inelastically scattered radioactive 16C nuclei. The measured mean lifetime is 77+/-14(stat)+/-19(syst) ps. The central value of mean lifetime corresponds to a B(E2;2+(1)-->0(+)) value of 0.63e(2) fm(4), or 0.26 Weisskopf units. The transition strength is found to be anomalously small compared to the empirically predicted value.
Journal Article↗
Effect of tacrolimus and cyclosporine on renal microcirculation and nitric oxide production.
OBJECTIVES: Cyclosporine (CSA) and tacrolimus (TAC) frequently induce nephrotoxicity and similar pathologic changes. Acute CSA-induced nephrotoxicity has been reported to be mediated by activation of vasoconstrictors such as endothelin. The purpose of the present study was to investigate the acute effects of TAC and CSA on the renal microcirculation and upon a vasodilator such as nitric oxide (NO) production. METHODS: Renal blood flow (RBF) in the microcirculation was measured by a Laser Doppler flow meter in uninephrectomised rats. RBF, mean arterial pressure (MAP), and renal vascular resistance (RVR) were measured in the following groups: (a) TAC (0.1 to 2.0 mg/kg/h, n = 3 approximately 6); CSA (20 and 50 mg/kg/h, n = 5); (b) L-NAME (10 mg/kg), an NO synthase inhibitor, 8 minutes prior to TAC (0.5 and 1.5 mg/kg/h, n = 5), or CSA (20 and 50 mg/kg/h, n = 5). Stable NO end-products, serum NO(2) and NO(3), were measured by the Griess method (n = 5). RESULTS: None of the parameters were changed by TAC alone, whereas TAC with L-NAME significantly reduced RBF (-28 +/- 7%) and increased RVR (46 +/- 17%) in a dose-dependent manner. CSA alone significantly reduced RBF (-37 +/- 6%) and increased RVR (69 +/- 22%) without any changes in MAP. The effects of CSA were enhanced by L-NAME. Serum concentration of NO(2) + NO(3) was significantly reduced by both L-NAME alone and CSA (50 mg/kg) (P < .05), while there were no changes with TAC (1.5 mg/kg). CONCLUSIONS: Blockade of NO production enhance the vasoconstrictive effect of CSA, and unmasked such an effect of TAC. These results suggest that the nephrotoxicity of CSA and TAC may involve the NO system.
Animals↗
Inhibition of the extracellular signal-regulated kinase (ERK) pathway and the induction of radioresistance in rat 3Y1 cells.
PURPOSE: Activation of the extracellular signal-regulated kinase (ERK) pathway generally results in stimulation of cell growth and confers a survival advantage. However, the potential involvement of this pathway in cellular radiosensitivity remains unclear. The study was designed to examine whether the ERK pathway affects intrinsic radiosensitivity in mammalian cells. MATERIALS AND METHODS: Exponentially growing rat 3Y1 cells were used. A specific inhibitor of mitogen-activated ERK kinase (MEK), PD98059, was used to inhibit the ERK pathway. In addition, kinase-deficient MEK was expressed in cells to inhibit the pathway in a dominant-negative manner. Activation of ERK was visualized by Western blot using an antibody that recognizes the phosphorylated form of ERK. Radiosensitivity was evaluated by a colony-forming assay. RESULTS: 3Y1 cells treated with PD98059 exhibited a significant inhibition of cell proliferation and radiation-induced transient activation of ERK. Unexpectedly, it was found that the inhibitor enhanced clonogenic radioresistance. This effect on radioresistance was confirmed by expression of kinase-deficient MEK. Apoptotic activities following irradiation were significantly inhibited in PD98059-treated cells as determined by caspase-3-like activities. CONCLUSION: Activation of the MEK/ERK pathway increases clonogenic radiosensitivity in rat 3Y1 cells. These findings, together with a variety of other data, suggest that there might be clinical implications in targeting the MEK/ERK pathway in radiotherapy.
Animals↗
A case of plasmacytic hyperplasia arising in a kidney allograft salvaged with immunosuppression reduction alone.
Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication of organ transplantation. Plasmacytic hyperplasia (PH) is thought of as the mildest form of PTLD; however, a graftectomy is necessary in most situations. We experienced an interesting case of PH arising in a kidney allograft, which could be relieved with a reduction in immunosuppression. A 27-year-old female underwent a living-related kidney transplantation. A 3-month non-episode protocol biopsy unexpectedly showed the devastating appearance of polymorphic plasma cell infiltration into the graft intersitium, compatible with PH. The PH was located in the graft by radiographic examinations. The infiltration of plasma cell disappeared completely on the 6-month graft biopsy specimen following immunosuppression reduction and the graft is functioning, although it was damaged by a subsequent acute rejection. Our present case indicates that some PTLD can be completely cured with a reduction in immunosuppression alone. The diagnostic modality for the evaluation of PTLD cell extinction is necessary to maintain graft function with adequate immunosuppression thereafter.
Adult↗
Coronary risk factors in Kawasaki disease treated with additional gammaglobulin.
AIMS: To assess the hypothesis that an additional intravenous gammaglobulin (IVGG) infusion, if administered early, may prevent coronary artery lesions (CAL) in patients with Kawasaki disease (KD) who do not respond to initial IVGG therapy. METHODS: Forty four KD patients (17 with CAL and 27 without CAL), treated with additional IVGG because of persistent or recrudescent fever after initial IVGG therapy, were studied. Main outcome measures were the presence of CAL by echocardiography and the number of febrile days before and after start of additional IVGG infusion (pre- and post-additional IVGG). RESULTS: In univariate analyses, risk factors for CAL were the number of febrile days pre-additional IVGG, the number of febrile days post-additional IVGG, the number of days that initial IVGG was divided over, the white blood cell count pre- and post-additional IVGG, and the C reactive protein concentration pre-additional IVGG. In a multivariate analysis, the only independent risk factor was the number of febrile days pre-additional IVGG (> or =10 days; odds ratio 7.86; 95% CI 1.44 to 42.8; p = 0.02). CONCLUSIONS: Among KD patients with persistent or recrudescent fever after initial IVGG therapy, administration of additional IVGG before the first 10 febrile days was associated with a decreased prevalence of CAL, when compared with the prevalence in those who were retreated later. An additional IVGG infusion, if administered early, may prevent CAL in initial IVGG non-responders.
Adrenal Cortex Hormones↗
Synthesis of copper octabromotetracarboranylphenylporphyrin for boron neutron capture therapy and its toxicity and biodistribution in tumour-bearing mice.
Copper tetracarboranyltetraphenylporphyrin (CuTCPH) is a minimally toxic carborane-containing porphyrin that has safely delivered high concentrations of boron for experimental boron neutron capture therapy (BNCT). Copper octabromotetracarboranylphenylporphyrin (CuTCPBr), synthesized by bromination of CuTCPH, is one of several new minimally toxic analogues of CuTCPH being studied in our laboratory, which could possess comparable or better tumour-targeting properties with enhanced tumour cytotoxicity. Its biodistribution, biokinetics and toxicity in mice with subcutaneous EMT-6 (mammary) or SCCVII (squamous cell) carcinomas were compared with those of CuTCPH. The administration of approximately 200 mg kg(-1) of either porphyrin in six intraperitoneal injections over 2 days had no apparent effect, but administration of approximately 400 mg kg(-1) slightly lowered body weights, elevated alanine and aspartate transaminase activities in blood plasma, and depressed blood platelet counts for several days. Enzymes and platelets returned to normal within 5 days after those injections and body weights returned to normal within 2 weeks. High average concentrations of boron from either porphyrin were achieved in the two tumour models from a total dose of approximately 200 mg kg(-1). The high tumour boron concentration decreased slowly while concentrations in blood decreased rapidly. Boron concentrations in brain and skin were consistently lower than in tumour by a factor of 10 or more. Although either CuTCPH or CuTCPBr can be labelled with (64)Cu for imaging by positron emission tomography (PET), CuTCPBr can also be labelled by (76)Br, another PET-imageable nuclide.
Animals↗
Activation of the phosphatidylinositol-3' kinase pathway and DNA synthesis by a mutant insulin-like growth factor I receptor lacking the NPXY motif.
We have investigated the role of the NPXY motif in the insulin-like growth factor I receptor (IGF-IR) by focusing on the activation of the phosphatidylinositol-3' kinase (PI3-K) pathway and DNA synthesis following IGF-I stimulation. For this purpose, we established stable R-cell lines, which are deficient in endogenous IGF-IR, and express human IGF-IR lacking the whole NPEY(950) sequence (DeltaNPEY). The DeltaNPEY cells showed an apparent autophosphorylation of IGF-IR, albeit with reduced sensitivity to stimulation compared with cells expressing similar levels of wild-type IGF-IR. Activation of insulin receptor substrate (IRS)-1 and IRS-2 was severely impaired in DeltaNPEY cells even at high concentrations of IGF-I. However, recruitment of p85, a regulatory subunit of PI3-K, to activated IRS-2 was similar between the cell lines, but recruitment of p85 to IRS-1 was reduced in DeltaNPEY cells. Essentially similar levels of p85- or phosphotyrosine-associated PI3-K and Akt activities were observed between the cell lines, although the sensitivity to stimulation was reduced in DeltaNPEY cells. Activation of extracellular signal-regulated kinase and DNA synthesis were virtually unaffected by the mutation, in terms of both sensitivity to stimulation and responsiveness. DNA synthesis was completely inhibited by the PI3-K inhibitor, LY294002. These results indicate that the IGF-IR is able to activate the PI3-K pathway and induce DNA synthesis in a normal fashion without the NPXY motif when the receptor is fully activated.
Amino Acid Motifs↗
[Long-term application of percutaneous cardiopulmonary support system without systemic heparinization].
Though the amount of systemic heparin sodium administration was reduced after the introduction of heparin sodium-coating material to percutaneous cardiopulmonary support system (PCPS), bleeding due to heparin sodium is still the one of the major complications. In 2 patients of postcardiotomy cardiogenic shock, we neutralized heparin sodium by protamine sulfate administration immediately after the institution of PCPS and did not perform systemic heparinization until hemostasis was secured. The time on PCPS without heparin sodium was 37 hours in 1 patient and 91 hours in another patient. While systemic heparin sodium was not administered, activated clotting time (ACT) ranged from 109 to 148 sec and the bypass flow rate was maintained in more than 2.5 l/min. The exchange of the devices was unnecessary during the assistance and the patients were successfully weaned from PCPS without major complications. We conclude that systemic anticoagulation can be avoided in the case of life-threatening hemorrhage.
Aged↗
Search for nu(e) from the sun at Super-Kamiokande-I.
We present the results of a search for low energy nu(e) from the Sun using 1496 days of data from Super-Kamiokande-I. We observe no significant excess of events and set an upper limit for the conversion probability to nu(e) of the 8B solar neutrino. This conversion limit is 0.8% (90% C.L.) of the standard solar model's neutrino flux for total energy=8-20 MeV. We also set a flux limit for monochromatic nu(e) for E(nu(e))=10-17 MeV.
Journal Article↗
Search for supernova relic neutrinos at Super-Kamiokande.
A search for the relic neutrinos from all past core-collapse supernovae was conducted using 1496 days of data from the Super-Kamiokande detector. This analysis looked for electron-type antineutrinos that had produced a positron with an energy greater than 18 MeV. In the absence of a signal, 90% C.L. upper limits on the total flux were set for several theoretical models; these limits ranged from 20 to 130 macro nu(e) cm(-2) s(-1). Additionally, an upper bound of 1.2 macro nu(e) cm(-2) s(-1) was set for the supernova relic neutrino flux in the energy region E(nu)>19.3 MeV.
Journal Article↗