Biomedical subjects

Akio Mizutani

Publications and source records attributed to Akio Mizutani.

14 recordsLinked to original sources

PubMed2006

Reduced wavelength-dependent quarter-wave plate fabricated by a multilayered subwavelength structure.

We developed a novel fabrication method of a reduced wavelength-dependent quarter-wave plate (QWP) based on form birefringence of a multilayered subwavelength structure. The multilayered structure was constructed by depositing a high-refractive-index thin film on a subwavelength-structured substrate with a low refractive index. The surface structure of the substrate was shallow enough to be formed by a mass replication technology. A high-refractive-index subwavelength grating was formed on ridges of the substrate by sputtering Zn2SnO4 (refractive index of 2.03 at a wavelength of 633 nm). Moreover, since the grooves of the high-refractive-index grating were very deep and narrow, the dispersion of form birefringence suppressed the dependency of phase retardance on the wavelength of light in a limited spectral region. The phase retardance of the fabricated QWP was 89 degrees at a 633 nm wavelength and 79 degrees at a 785 nm wavelength.

Journal Article↗

PubMed2006

Recombinant human activated protein C improves pulmonary function in ovine acute lung injury resulting from smoke inhalation and sepsis.

OBJECTIVE: To investigate the effects of recombinant human activated protein C (rhAPC) on pulmonary function in acute lung injury (ALI) resulting from smoke inhalation in association with a bacterial challenge. DESIGN: Prospective, randomized, controlled, experimental animal study with repeated measurements. SETTING: Investigational intensive care unit at a university hospital. SUBJECTS: Eighteen sheep (37.2 +/- 1.0 kg) were operatively prepared and randomly allocated to either the sham, control, or rhAPC group (n = 6 each). After a tracheotomy had been performed, ALI was produced in the control and rhAPC group by insufflation of 4 sets of 12 breaths of cotton smoke. Then, a 30 mL suspension of live Pseudomonas aeruginosa bacteria (containing 2-5 x 10(11) colony forming units) was instilled into the lungs according to an established protocol. The sham group received only the vehicle, i.e., 4 sets of 12 breaths of room air and instillation of 30 mL normal saline. The sheep were studied in the awake state for 24 hrs and were ventilated with 100% oxygen. RhAPC (24 mug/kg/hr) was intravenously administered. The infusion was initiated 1 hr post-injury and lasted until the end of the experiment. The animals were resuscitated with Ringer's lactate solution to maintain constant pulmonary artery occlusion pressure. MEASUREMENTS AND MAIN RESULTS: In comparison with nontreatment in controls, the infusion of rhAPC significantly attenuated the fall in Pao2/Fio2 ratio (control group values were 521 +/- 22 at baseline [BL], 72 +/- 5 at 12 hrs, and 74 +/- 7 at 24 hrs, vs. rhAPC group values of 541 +/- 12 at BL, 151 +/- 29 at 12 hours [p < .05 vs. control], and 118 +/- 20 at 24 hrs), and significantly reduced the increase in pulmonary microvascular shunt fraction (Qs/Qt; control group at BL, 0.14 +/- 0.02, and at 24 hrs, 0.65 +/- 0.08; rhAPC group at BL, 0.24 +/- 0.04, and at 24 hrs, 0.45 +/- 0.02 [p < .05 vs. control]) and the increase in peak airway pressure (mbar; control group at BL, 20 +/- 1, and at 24 hrs, 36 +/- 4; rhAPC group at BL, 21 +/- 1, and at 24 hrs, 28 +/- 2 [p < .05 vs. control]). In addition, rhAPC limited the increase in lung 3-nitrotyrosine (after 24 hrs [%]: sham, 7 +/- 2; control, 17 +/- 1; rhAPC, 12 +/- 1 [p < .05 vs. control]), a reliable indicator of tissue injury. However, rhAPC failed to prevent lung edema formation. RhAPC-treated sheep showed no difference in activated clotting time or platelet count but exhibited less fibrin degradation products (1/6 animals) than did controls (4/6 animals). CONCLUSIONS: Recombinant human activated protein C attenuated ALI after smoke inhalation and bacterial challenge in sheep, without bleeding complications.

Airway Obstruction↗

PubMed2006

Estimation method for the light extraction efficiency of light-emitting elements with a rigorous grating diffraction theory.

The light extraction efficiency of a light-emitting element with microstructured surface is analyzed with a rigorous grating diffraction theory. The grating theory reveals an improvement of extraction efficiency due to diffraction of light by the surface microstructure. The simulation results show that the improvement of extraction efficiency is due mainly to the reflected diffraction rather than to the transmitted diffraction. A part of total-internal-reflection light is diffracted into directions at less than the critical angle. Extraction efficiency is improved by multiple reflection and diffraction of light in a high-refractive-index layer. We propose a simple design method for an efficient surface microstructure from the viewpoint of reflected diffraction.

Journal Article↗

PubMed2005

Effect of Ulinastatin, a human urinary trypsin inhibitor, on the oleic acid-induced acute lung injury in rats via the inhibition of activated leukocytes.

BACKGROUND: The acute respiratory distress syndrome (ARDS) is often caused by fat tissue embolism. One of the most common animal models of ARDS is produced by direct administration of oleic acid (OA). Activated leukocytes are critically involved in the pathological mechanism in this model. Human urinary trypsin inhibitor (UTI) is known to inhibit production of tumor necrosis factor (TNF)-alpha, which potently stimulates leukocyte activation. The purpose of this study was to clarify whether UTI improves OA-induced lung injury in rats by inhibiting activated leukocytes via TNF-alpha production. MATERIALS AND METHODS: Rats were subjected to a single intravenous administration of OA into the pedicle vein. Acute lung injury was evaluated by arterial blood gases and histological changes in lungs. Pulmonary vascular permeability, accumulation of neutrophils, and the levels of TNF-alpha in lung tissues were also examined. Rats were divided into four experimental groups: a sham operated, OA, OA + UTI, and OA + nitrogen mustard (NM)-induced leukocytopenia group. UTI was intravenously administered 30 min before OA administration. Leukocytopenia was induced by the administration of NM. RESULTS: UTI significantly improved the OA-induced histological changes for 4 h after OA administration. The OA-induced reduction of PaO2, the increase of pulmonary vascular permeability, and the levels of MPO activity and TNF-alpha in lung tissues were significantly improved in rats administrated UTI. The effects in the leukocytopenia group were similar to those in the UTI-administered group. CONCLUSION: Leukocytes play a critical role in the development of OA-induced lung injury. It was suggested that UTI contributed to the reduction in the OA-induced lung injury by inhibiting TNF-alpha and thereby suppressing leukocyte.

Acute Disease↗

PubMed2005

Olprinone reduces ischemia/reperfusion-induced acute renal injury in rats through enhancement of cAMP.

Activated leukocytes are implicated in development of ischemia/reperfusion (I/R)-induced organ injuries. Phosphodiesterase 3 inhibitors have anti-inflammatory effects by preventing cyclic adenosine monophosphate (cAMP) degradation. We examined the effects of olprinone, a specific phosphodiesterase 3 inhibitor, on I/R-induced acute renal injury model in rats. Forty-five minute renal I/R was induced in uni-nephrectomized rats. Rats were divided into a vehicle group, an olprinone group, and a dibutyril (DB) cAMP group. Olprinone (0.2 microg/kg/minute) infusion began 30 min after reperfusion and continued for 3 h. DBcAMP (5 mg/kg), a stable analog of cAMP, was intraperitoneally administered 5 min after reperfusion to clarify the effect of cAMP in our model. Olprinone reduced the I/R-induced increases in serum levels of blood urea nitrogen and creatinine, and improved histological changes, including acute tubular necrosis in the outer medulla. Hemodynamic status was not affected by olprinone. I/R-induced a decrease in renal tissue blood flow, an increase in renal vascular permeability, and an enhancement of leukocyte activation, reflected by renal tissue levels of myeloperoxidase activity, and the tissue levels of cytokine-induced neutrophil chemoattractant (an equivalent of human interleukin 8) and tumor necrosis factor-alpha were all significantly decreased by olprinone. Olprinone also increased the renal tissue and plasma levels of cAMP in rats subjected to renal I/R. DBcAMP showed similar effects. Our results indicated that olprinone reduced the I/R-induced acute renal injury, probably by inhibiting leukocyte activation. The effects of olprinone could be explained through its action on cAMP levels.

Animals↗

PubMed2005

Recto-peritoneal fistula following transperineal prostate biopsy.

A recto-peritoneal fistula is an extremely rare complication after prostate biopsy. We report herein on a peritonitis arising from a recto-peritoneal fistula 5 days after undergoing prostate biopsy. To our knowledge, this is the first case of recto-peritoneal fistula following transperineal needle biopsy of the prostate in the published literature.

Abdominal Abscess↗

PubMed2005

Numerical study on an asymmetric guided-mode resonant grating with a Kerr medium for optical switching.

Optical switching effects of a guided-mode resonant grating (GMRG) with a Kerr medium have been simulated with the nonlinear finite differential time domain (FDTD) method. An asymmetric waveguide grating with a large second spatial harmonic component has been proposed for the optical switch. Resonant reflection occurs at both of the band-edge wavelengths. These wavelengths are used for the pump light and the probe light. The enhanced electric field of the pump light changes the resonant wavelength for the probe light as a result of the Kerr effect. We designed the GMRG with resonant wavelengths of 1489.6 and 1630 nm, which were used for the pump light and the probe light, respectively. When the grating material has a third-order susceptibility chi(3) of 8.5 x 10(-10) esu, the transmittance of the probe light changes from 0 to 80% by increasing the intensity of the pump light from 0 to 60 kW/mm2.

Journal Article↗

PubMed2004

[Colforsin daropate does not affect the cerebral blood-flow in cardiac surgery patients under cardiopulmonary bypass].

BACKGROUND: Cerebral blood flow partly plays a pivotal role in cerebral complications among cardiac surgery patients. We evaluated the effect of colforsin daropate (colforsin) on cerebral blood flow in cardiac surgery patients under cardiopulmonary bypass (CPB) by transcranial Doppler sonography (TCD). METHODS: Eighteen patients scheduled for coronary artery bypass surgery under CPB were assigned randomly to two groups:colforsin group (n=9) and control group (n=9). We assessed cardiac function by measuring cardiac index (CI) and systemic vascular resistance index (SVRI). Cerebral blood flow was evaluated by measuring the peak systolic blood flow velocity (Vs), end-diastolic blood flow velocity (Vd) together with mean blood flow velocity (Vm), and calculated the pulsatility index (PI) in the left carotid siphon by TCD. After baseline measurement, the colforsin loading dosage was increased from 0.25 to 0.5 microg x kg(-1) x min(-1) in colforsin group every 60 minutes. RESULTS: Colforsin significantly increased CI and decreased SVRI compared with pre-levels. In both groups there were no significant changes in Vs, Vd, Vm and PI. CONCLUSIONS: We have demonstrated that colforsin is effective for hemodynamics without cerebral blood flow change in cardiac surgery patients under cardiopulmonary bypass.

Aged↗

PubMed2003

Inducible nitric oxide synthase dimerization inhibitor prevents cardiovascular and renal morbidity in sheep with combined burn and smoke inhalation injury.

Inducible nitric oxide synthase (iNOS) is implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). ARDS treatment is frequently complicated by significant extrapulmonary comorbidity. This study was designed to clarify the role of iNOS in mediating extrapulmonary comorbidity in sheep after combined burn and smoke inhalation injuries using a potent and highly selective iNOS dimerization inhibitor, BBS-2. Twenty-two female sheep were operatively prepared. After 5 days of recovery, tracheostomy was performed under ketamine-halothane anesthesia. Sheep were given a 40% total body surface third-degree burns and insufflated with cotton smoke (48 breaths, <40 degrees C). Sheep were divided into four groups: noninjured and nontreated (sham group; n = 6), noninjured but treated with BBS-2 (sham/BBS-2 group; n = 4), injured but nontreated (control group, n = 6), and injured but treated with 100 microg.kg-1.h-1 BBS-2 (BBS-2 group; n = 6). Evaluation was in a laboratory intensive care unit setting for 48 h. The sham group had stable cardiopulmonary and systemic hemodynamics. Control animals showed multiple signs of morbidity. Decreased left ventricular stroke work index and stroke volume index with elevated left atrial pressure indicated myocardial depression. Systemic vascular leak was evidenced by robust hemoconcentration, decreased plasma oncotic pressure, and increased transvascular fluid flux into the lymphatic system. Finally, severely impaired renal function (urinary output) was associated with adverse net fluid balance. Treatment with BBS-2 prevented all these morbidities without adversely effecting cardiovascular hemodynamics such as cardiac index and mean arterial pressure. The results identify a major role for iNOS in mediating extrapulmonary comorbidity in a clinically relevant and severe trauma model and support the use of highly selective iNOS inhibitors as novel treatments in critical care medicine.

Animals↗

PubMed2003

Inhibition of neuronal nitric oxide synthase by 7-nitroindazole attenuates acute lung injury in an ovine model.

Nitric oxide (NO) has been shown to play a major role in acute lung injury (ALI) after smoke inhalation. In the present study, we developed an ovine sepsis model, created by exposing sheep to smoke inhalation followed by instillation of bacteria into the airway, that mimics human sepsis and pneumonia. We hypothesized that the inhibition of neuronal NO synthase (nNOS) might be beneficial in treating ALI associated with this model. Female sheep (n = 26) were surgically prepared for the study and given a tracheostomy. This was followed by insufflation of 48 breaths of cotton smoke (40 degrees C) into the airway of each animal and subsequent instillation of live Pseudomonas aeruginosa [5 x 10(11) colony forming units (CFU)] into each sheep's lung. All sheep were mechanically ventilated using 100% O2. Continuous infusion of 7-nitroindazole (7-NI), an nNOS inhibitor, NG-monomethyl-l-arginine (l-NMMA), a nonspecific NOS inhibitor, or aminoguanidine (AG), an inducible NOS inhibitor, was started 1 h after insult. The administration of 7-NI improved pulmonary gas exchange (PaO2/FiO2; where PaO2 is arterial PO2 and FiO2 is fractional inspired oxygen concentration) and pulmonary shunt fraction and attenuated the increase in lung wet-to-dry weight ratio seen in the nontreated sheep. Histologically, 7-NI prevented airway obstruction. The increase in airway blood flow after injury in the nontreated group was significantly inhibited by 7-NI. The increase in plasma concentration of nitrate and nitrite (NOx) was inhibited by 7-NI as well. Posttreatment with l-NMMA improved the pulmonary gas exchange, but AG did not. The results of the present study show that nNOS may be involved in the pathogenesis of ALI after smoke inhalation injury followed by bacterial instillation in the airway.

Acute Disease↗

PubMed2003

The inducible nitric oxide synthase inhibitor BBS-2 prevents acute lung injury in sheep after burn and smoke inhalation injury.

In this study we examined the role of inducible nitric oxide synthase (iNOS) in acute respiratory distress syndrome (ARDS) in sheep with severe combined burn and smoke inhalation injury. BBS-2, a potent and highly selective iNOS dimerization inhibitor, was used to exclude effects on the endothelial and neuronal NOS isoforms. Seven days after surgical recovery, sheep were given a burn (40% of total body surface, 3rd degree) and insufflated with cotton smoke (48 breaths, < 40 degrees C) under anesthesia. BBS-2 was provided by constant infusion at 100 microg/kg/hour, beginning 1 hour after injury. During 48 hours, control sheep developed multiple signs of ARDS. These included decreased pulmonary gas exchange, increased pulmonary edema, abnormal lung compliance, and extensive airway obstruction. These pathologies were associated with a large increase in tracheal blood flow and elevated plasma NO2-/NO3- (NOx) levels. These variables were all stable in sham animals. Treatment of injured sheep with BBS-2 attenuated the increases in tracheal blood flow and plasma NOx levels, and significantly attenuated all the pulmonary pathologies that were noted. The results provide definitive evidence that iNOS is a key mediator of pulmonary pathology in sheep with ARDS resulting from combined burn and smoke inhalation injury.

Animals↗

PubMed2002

Antithrombin reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation through promotion of prostacyclin production.

Antithrombin (AT) supplementation in patients with severe sepsis has been shown to improve organ failures in which activated leukocytes are critically involved. However, the precise mechanism(s) for the therapeutic effects of AT is not well understood. We examined in rats whether AT reduces ischemia/reperfusion (I/R)-induced renal injury by inhibiting leukocyte activation. AT markedly reduced the I/R-induced renal dysfunction and histologic changes, whereas neither dansyl glutamylglycylarginyl chloromethyl ketone-treated factor Xa (DEGR-F.Xa), a selective inhibitor of thrombin generation, nor Trp49-modified AT, which lacks affinity for heparin, had any effect. Renal tissue levels of 6-keto-PGF(1 alpha), a stable metabolite of prostacyclin (PGI(2)), increased after renal I/R. AT enhanced the I/R-induced increases in renal tissue levels of 6-keto-PGF(1 alpha), whereas neither DEGR-F.Xa nor Trp49-modified AT had any effect. AT significantly inhibited I/R-induced decrease in renal tissue blood flow and the increase in the vascular permeability. Ischemia/reperfusion-induced increases in renal tissue levels of tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and myeloperoxidase were significantly inhibited in animals given AT. Pretreatment of animals with indomethacin reversed the effects induced by AT. Iloprost, an analog of PGI(2), produced effects similar to those induced by AT. These observations strongly suggest that AT reduces the I/R-induced renal injury by inhibiting leukocyte activation. The therapeutic effects of AT might be mainly mediated by PGI(2) released from endothelial cells through interaction of AT with cell surface glycosaminoglycans.

6-Ketoprostaglandin F1 alpha↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2002

Guided-mode resonant grating filter with an antireflection structured surface.

We describe a new structure of guided-mode resonant grating (GMRG) filters with low sideband reflectance. This GMRG filter consists of a high-index thin film on an antireflective structured surface called "moth-eye structure." Since the high-index film undulates along the surface structure, the film acts as a modulated optical waveguide. An incident light wave satisfying a resonant condition is reflected by the GMRG filter, and nonresonant light waves pass through the filter. This GMRG filter is valid for reducing reflection of nonresonant light waves in a wide spectral range. The resonant reflection of this new filter was investigated by numerical calculation based on an electromagnetic grating analysis. In the case of a triangular antireflective surface structure whose thickness is 2x greater than its period, the sideband reflectance for nonresonant light waves was lower than 0.5% for TM-polarized light in a wide range of wavelengths.

Journal Article↗