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Yoshiaki Inoue

Publications and source records attributed to Yoshiaki Inoue.

16 recordsLinked to original sources

ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors.

Cells must amplify external signals to orient and migrate in chemotactic gradient fields. We find that human neutrophils release adenosine triphosphate (ATP) from the leading edge of the cell surface to amplify chemotactic signals and direct cell orientation by feedback through P2Y2 nucleotide receptors. Neutrophils rapidly hydrolyze released ATP to adenosine that then acts via A3-type adenosine receptors, which are recruited to the leading edge, to promote cell migration. Thus, ATP release and autocrine feedback through P2Y2 and A3 receptors provide signal amplification, controlling gradient sensing and migration of neutrophils.

Adenosine↗

Extension of the inferior vena cava into the posteroinferior right atrium.

BACKGROUND: The inferior vena cava (IVC) is obliquely connected to the right atrium (RA), and often a low-voltage area is observed in the posteroinferior RA. OBJECTIVES: The purpose of this study was investigate the size of the IVC extension into RA and its anatomic background. METHODS: We investigated 30 human hearts [11 men and 19 women; mean age 79 +/- 10 years; 7 cardiac deaths (group A) and 23 noncardiac deaths (group B)]. After obtaining macroscopic measurements around the RA-IVC junction, serial sections were cut and examined histologically. We defined a horizontal baseline at the level of the cavotricuspid isthmus and measured (1) the length of IVC extension, which was defined as the distance from the baseline to the top of the RA-IVC junction, and (2) the width of the RA-IVC junction at the baseline level. RESULTS: The top of the RA-IVC junction was always located in the posteroinferior RA. The mean length of the IVC extension was 17.6 +/- 6.6 mm, and the mean width was 29.6 +/- 7.5 mm. The IVC extension was wider in group A than in group B (35.8 +/- 9.0 mm vs 27.5 +/- 5.9 mm; P = .0277). The right and left borders of the RA-IVC junction corresponded to the reflection of the pericardium. Histologic examination showed no myocardium in the IVC extension. CONCLUSION: The IVC extension into the posteroinferior RA always exists and varies in size. Because this area lacks myocardium, it is important to consider when analyzing catheter mapping from this area.

Aged↗

Lithium and dementia: a preliminary study.

Recent studies have shown that lithium may block the accumulation of amyloid-beta (Abeta) peptides and to inhibit the hyperphosphorylation of tau via the inhibition of GSK-3alpha in the brain of mice. The purpose of the present study is to examine whether lithium could potentially be effective for the prevention of Alzheimer's disease. We investigated the clinical records of 1,423 outpatients at a university psychiatric outpatient clinic and classified patients according to the following criteria: (a) absence of a diagnosis of dementia, (b) age 60 years or older, and (c) lithium had been prescribed and/or was currently prescribed. We compared these patients with randomly selected age and gender matched control group who had never been prescribed lithium. Despite no significant difference in MMSE scores between the lithium group, which consisted of patients receiving lithium treatment, and the control group, those who had previously received lithium and/or were currently prescribed lithium had significantly better MMSE scores than the control patients. The findings provide partial evidence to support the contention that lithium could offer hope as a preventive treatment for Alzheimer's disease. Further prospective studies with a large number of patients are warranted to investigate this potentially important effect.

Aged↗

A neutrophil elastase inhibitor, sivelestat, improves leukocyte deformability in patients with acute lung injury.

BACKGROUND: The objective of this study was to evaluate whether the neutrophil elastase (NE) inhibitor, sivelestat, improves leukocyte deformability and pulmonary function in patients with acute lung injury (ALI). PATIENTS AND METHODS: Twenty-four patients with systemic inflammatory response syndrome (SIRS) were divided into two groups: those with ALI (ALI group, n = 14), and those without ALI (non-ALI group, n = 10). Within 72 hours after the diagnosis, we measured the total leukocyte count (TLC), C-reactive protein (CRP) level, NE concentration, APACHE II score, Goris multiple organ failure (MOF) index, respiratory index (RI), lung injury score (LIS), and oxygenation index (P/F ratio). Leukocyte deformability was examined with a microchannel array etched on a single-crystal silicon tip that simulates the microvasculature. The number of obstructed microchannels (NOM) because of stiffened neutrophils and transit time (TT), defined as the time needed for 100 microL of whole blood to pass through the microchannels, were determined. We then administered sivelestat (4.8 mg/kg/d) to nine ALI patients (sivelestat group) for 5 days and compared with seven ALI patients treated previously without sivelestat (conventional group). The factors described above were measured before and 5 days after treatment. RESULTS: There were no significant differences in age, TLC, CRP, APACHE II score, and MOF index between ALI and non-ALI group. RI and LIS were higher and the P/F ratio was significantly lower in the ALI group than in the non-ALI group. NE concentration, NOM, and TT were significantly higher in the ALI group than in the non-ALI group (p < 0.05). After 5 days of treatment with sivelestat, the APACHE II score, MOF index, RI, LIS, NE concentration, TT, and NOM were lower and the P/F ratio was significantly higher than baseline values and those in the conventional group (p < 0.05). CONCLUSION: NE concentration and neutrophil rigidity are significantly increased in SIRS patients with ALI. Sivelestat appears to reduce NE concentration and neutrophil stiffness and improve pulmonary oxygenation in patients with ALI.

APACHE↗

Preparation of ferrimagnetic magnetite microspheres for in situ hyperthermic treatment of cancer.

Ferrimagnetic microspheres 20-30 microm in diameter are useful as thermoseeds for inducing hyperthermia in cancers, especially for tumors located deep inside the body. The microspheres are entrapped in the capillary bed of the tumors when they are implanted through blood vessels and heat cancers locally by their hysteresis loss when placed under an alternating magnetic field. In the present study, preparation of magnetite (Fe(3)O(4)) microspheres 20-30 microm in diameter was attempted by melting powders in high-frequency induction thermal plasma, and by precipitation from aqueous solution. The microspheres prepared by melting powders in high-frequency induction thermal plasma were composed of a large amount of Fe(3)O(4) and a small amount of wustite (FeO), and those subsequently heat treated at 600 degrees C for 1 h under 5.1 x 10(3) Pa were fully composed of Fe(3)O(4) 1 microm in size. The saturation magnetization and coercive force of the heat-treated microspheres were 92 emu g(-1) and 50 Oe, respectively. The heat generation of the heat-treated microspheres was estimated to be 10 Wg(-1), under 300 Oe and 100 kHz. The microspheres prepared by precipitation from aqueous solution consisted of beta-FeOOH, and those subsequently heat treated at 400 degrees C for 1 h in a 70% CO(2) + 30% H(2) atmosphere consisted of Fe(3)O(4) crystals 50 nm in size. The saturation magnetization and coercive force of the heat-treated microspheres were 53 emu g(-1) and 156 Oe, respectively. The heat generation of the heat-treated microspheres was estimated to be 41 Wg(-1), under 300 Oe and 100 kHz. The latter microspheres are believed to be promising thermoseeds for hyperthermic treatment of cancer.

Animals↗

Changes in cerebral blood flow from the acute to the chronic phase of severe head injury.

We studied cerebral blood flow (CBF) in the transition from the acute to the chronic phase of severe head injury in order to determine patterns of change in relation to neurological outcome. We measured CBF with stable xenon-enhanced computed tomography (Xe-CT) in 20 consecutive patients at 1, 2, 3, 4, and 6 weeks after severe head injury, and analyzed the relation between the pattern of change in CBF and neurological outcome at 6 months after injury. CBF values were significantly lower in the brain-injured patients than in 14 healthy volunteers, except at 3 weeks after injury, when CBF increased in the patients to a value that did not differ significantly from that in the normal volunteers. We therefore focused on the change in CBF at 3 weeks after injury. We separated the 20 brain-injured patients into two subgroups, of which the first (subgroup A) consisted of nine patients whose CBF had returned to normal by week 3 post-injury, while the second (subgroup B) consisted of 11 patients whose CBF was subnormal at week 3 post-injury. CBF was significantly higher in subgroup A than in subgroup B at 2 weeks post-injury (p < 0.05). CBF in subgroup B remained significantly lower than that in subgroup A throughout the study period. At 6 months post-injury, subgroup A had a significantly better neurological outcome than did subgroup B (p < 0.05). We conclude that patients whose CBF returns to normal at 2-3 weeks following severe traumatic brain injury after being abnormally low in the acute phase of injury can be expected to achieve a good neurological outcome.

Adolescent↗

Protective effects of a selective neutrophil elastase inhibitor (sivelestat) on lipopolysaccharide-induced acute dysfunction of the pulmonary microcirculation.

OBJECTIVE: The purpose of this study was to evaluate the effect of a neutrophil elastase inhibitor, sivelestat, on lipopolysaccharide-induced acute lung injury through analysis of hemodynamic changes in the pulmonary microcirculation. DESIGN: Randomized animal study. SETTING: Medical school laboratory. SUBJECTS: Twenty-seven Wistar rats (15 rats for microspectroscopic observations, 12 rats for measurements of neutrophil elastase activity and wet-to-dry ratio). INTERVENTIONS: Thoracosternotomy was performed on male Wistar rats under continuous anesthesia and mechanical ventilation. Rats were divided into three groups (n = 5 each groups) on the basis of the reagent used: lipopolysaccharide group (100 microg/kg lipopolysaccharide intravenously), sivelestat group (10 mg/kg sivelestat; 100 microg/kg lipopolysaccharide intravenously), and control group (saline only, intravenously). MEASUREMENTS AND MAIN RESULTS: We measured morphologic changes and hemodynamic variables, including tissue blood flow, erythrocyte velocity, erythrocyte count, thickness of interalveolar septa, and leukocyte adhesion in the pulmonary microcirculation, with a video-rate (33 msec/frame) dual-spot microspectroscopy system (DSMSS) and a laser-Doppler flowmeter. Blood-free wet-to-dry ratio and neutrophil elastase activity in bronchoalveolar lavage fluid, serum, and supernatant of lung homogenate were measured in another set of experiments (n = 4 for each group). Sixty minutes after lipopolysaccharide administration, severe thickening of the interalveolar septa was observed in the lipopolysaccharide but not the sivelestat group. In the lipopolysaccharide group, DSMSS measurements of erythrocyte velocity and hemoglobin oxygenation in single capillaries were decreased significantly (vs. control p < .05, vs. sivelestat p < .01), whereas tissue blood flow and erythrocyte velocity measurements from laser-Doppler flowmeter were increased significantly (vs. control p < .05, vs. sivelestat p < .01). The number of adherent leukocytes was increased significantly in the lipopolysaccharide group at 30, 45, and 60 mins after lipopolysaccharide administration (vs. control p < .01, vs. sivelestat p < .05). The number of adherent leukocytes did not increase in the sivelestat group. The wet-to-dry ratio was significantly higher in the lipopolysaccharide group than in control (p < .05) and sivelestat (p < .05) groups. Neutrophil elastase activities in the bronchoalveolar lavage fluid, serum, and lung tissue were all significantly lower in the sivelestat group than in the lipopolysaccharide group (p < .05). CONCLUSIONS: Lipopolysaccharide induces leukocyte adhesion in the pulmonary microcirculation, resulting in decreased tissue hemoglobin oxygen and alveolar and interstitial edema. The selective neutrophil elastase inhibitor sivelestat reduces neutrophil elastase activity and attenuates acute changes in the pulmonary microcirculation.

Analysis of Variance↗

Serial changes in leukocyte deformability and whole blood rheology in patients with sepsis or trauma.

BACKGROUND: The objective of this study was to investigate serial changes in leukocyte deformability and rheologic properties of whole blood in patients with sepsis or trauma. METHODS: Seventeen sepsis patients and 22 trauma patients were enrolled. Leukocyte deformability and rheologic properties of whole blood were determined with the use of a microchannel array etched on a single-crystal silicon tip, simulating the microvasculature. The number of obstructed microchannels (NOM) was used as a measure of leukocyte deformability. Transit time (TT), i.e., the time taken for 100 microL of whole blood to pass through the microchannel array was also used as rheologic measure. Oxidative activity and F-actin content of neutrophils was measured in patients with sepsis. RESULTS: NOM and TT significantly increased in patients when sepsis was diagnosed. In survivors, NOM and TT decreased at the time of recovery from sepsis, but in non-survivors values remained high. Oxidative activity and F-actin content of neutrophils increased significantly as leukocyte deformability decreased. In patients with severe trauma, NOM and TT increased after injury and decreased by the time of recovery from the critical stage. CONCLUSION: We conclude that leukocyte deformability decreases in patients with sepsis or severe trauma and that this change negatively affects rheologic properties of whole blood.

Actins↗

[Smoke inhalation injury: diagnosis and respiratory management].

Smoke inhalation is a significant comorbid factor following major thermal injury. Smoke exposure is only a trigger for the sequence of events responsible for the development of inhalation injury. Noxious chemicals generated by incomplete combustion injure the exposed bronchoepithelium and stimulate the release of chemical mediators that cause a progressive inflammatory process. Airway inflammation and pulmonary edema impair gas exchange and increase the susceptibility to pulmonary infection. Earlier diagnosis and treatment of inhalation injury is an important element to improve the clinical course of severe burn patients. The American Burn Association, however, recently concluded that there are insufficient data to support a treatment standard for the diagnosis of inhalation injury. At present, the diagnosis of inhalation injury is supported by the combination of history, physical examination, bronchoscopy, and laboratory findings For accurate diagnosis of inhalation injury, helical CT scanning and examination to detect activated leukocytes in bronchoalveolar lavage fluid may be warranted. In the respiratory management of inhalation injury, repeated removal of pseudomembrane by fiberoptic bronchoscopy and the use of adequate PEEP to avoid airway obstruction are essential. High-frequency percussive ventilation can be a suitable mode of ventilation for inhalation injury.

Bronchoalveolar Lavage Fluid↗

Changes in CSF S100B and cytokine concentrations in early-phase severe traumatic brain injury.

S100B protein (S100B) has been described as a marker of brain injury. Various cytokines also increase in the cerebrospinal fluid (CSF) of patients with severe traumatic brain injury (TBI). Thus, we investigated early changes in the concentrations of CSF S100B and various cytokines after TBI and evaluated the relations of both S100B and cytokines to intracranial pressure (ICP) and prognosis. Twenty-three patients with severe TBI and a Glasgow Coma Scale score of 8 or less on admission were included in this study. CSF and serum samples were obtained on admission and at 6, 12, 24, 48, 72, and 96 h after injury. CSF concentrations of S100B and CSF and serum concentrations of five cytokines (IL-1beta, TNF-alpha, IL-6, IL-8, and IL-10) were measured and compared. The CSF S100B concentration was increased for 6 h after injury and decreased thereafter. The CSF concentrations of IL-6 and IL-8 peaked within 6 h after injury; other cytokines (IL-1beta, TNF-alpha, and IL-10) were elevated for 24 h after injury and gradually decreased thereafter. Peak CSF S100B concentrations correlated significantly with ICP determined at the time CSF samples were taken (r = 0.729, P < 0.0001). For the cytokines investigated, only the peak CSF IL-1beta concentration correlated significantly and positively with the peak CSF S100B concentration (r = 0.397, P < 0.005). Peak CSF concentrations of S100B (1649 +/- 415 microg/L, mean +/- SEM) and IL-1beta (16.5 +/- 3.3 pg/mL) in the 6 patients with high ICP were significantly higher than those (233 +/- 67 microg/L, 7.6 +/- 1.7 pg/mL, respectively) in the 17 patients with low ICP (P < 0.05). The CSF S100B concentration (1231 +/- 378 microg/L) in eight patients with an unfavorable outcome was significantly higher than that (267 +/- 108 microg/L) in 15 patients with a favorable outcome (P < 0.05). The CSF IL-1beta concentration (14.8 +/- 3.4 pg/mL) in eight patients with an unfavorable outcome tended to be higher than that (7.3 +/- 1.5 pg/mL) in 15 patients with a favorable outcome (P = 0.057). CSF concentrations of S100B and cytokines peak within 24 h after severe TBI and decrease gradually thereafter. CSF S100B and IL-1beta may be useful as predictors of outcome in cases of severe TBI.

Adult↗

Preparation of ceramic microspheres for in situ radiotherapy of deep-seated cancer.

Radiotherapy is one of the most effective treatments for cancers. However, external irradiation provides only small doses to deep-seated cancers, and often causes damage to healthy tissues. It has been reported that 20-30 microm diameter 17Y(2)O(3)-19Al(2)O(3)-64SiO(2) (mol%) glass microspheres are useful for the in situ irradiation of cancers. Yttrium-89 (89Y) in this glass can be neutron bombarded to form the beta-emitter 90Y (half-life=64.1h). When injected in the vicinity of the cancer, such activated glass microspheres can provide a large localized dose of beta-radiation. The Y(2)O(3) content of the glass in the microspheres is limited to only 17 mol%. Chemically durable microspheres with a higher Y(2)O(3) content need to be developed. Phosphorus-31 (31P) with 100% natural abundance can also be activated by neutron bombardment to form the beta-emitter 32P (half-life=14.3d). Chemically durable microspheres containing a high phosphorus content are expected to be more effective for cancer treatment. We prepared pure Y(2)O(3) and YPO(4) microspheres using a high-frequency induction thermal plasma melting technique, and investigated the resulting structure and chemical durability. We successfully prepared smooth, highly spherical polycrystalline Y(2)O(3) and YPO(4) microspheres with diameters in the range 20-30 microm. Both the Y(2)O(3) and YPO(4) microspheres showed high chemical durability in saline solutions buffered at pH=6 and 7. These microspheres are expected to be more effective than the conventional glass microspheres for the in situ radiotherapy of cancer.

Brachytherapy↗

Efficacy of moderate hypothermia in patients with severe head injury and intracranial hypertension refractory to mild hypothermia.

OBJECT: This study was performed to determine whether moderate hypothermia (31 degrees C) improves clinical outcome in severely head injured patients whose intracranial hypertension cannot be controlled using mild hypothermia (34 degrees C). METHODS: Twenty-two consecutive severely head injured patients who fulfilled the following criteria were included in this study: an intracranial pressure (ICP) that remained higher than 40 mm Hg despite the use of mild hypothermia combined with conventional therapies; and a Glasgow Coma Scale score of 8 or less on admission. After the failure of mild hypothermia in combination with conventional therapies; patients were exposed to moderate hypothermia as quickly as possible. As brain temperature was reduced from 34 to 31 degrees C, the volume of intravenous fluid infusion was increased significantly from 1.9 +/- 0.9 to 2.6 +/- 1.2 mg/kg/hr (p < 0.01), and the dose of dopamine infusion increased significantly from 4.3 +/- 3.1 to 8.2 +/- 4.4 microg/kg/min (p < 0.01). Nevertheless, mean arterial blood pressure and heart rate decreased significantly from 97.1 +/- 13.1 to 85.1 +/- 10.5 mm Hg (p < 0.01) and from 92.2 +/- 13.8 to 72.2 +/- 14.3 beats/minute at (p < 0.01) at 34 and 31 degrees C, respectively. Arterial base excess was significantly aggravated from -3.3 +/- 4 at 34 degrees C to -5.6 +/- 5.4 mEq/L (at 31 degrees C; p < 0.05). Likewise, serum potassium concentration, white blood cell counts, and platelet counts at 31 degrees C decreased significantly compared with those at 34 degrees C (p < 0.01). In 19 (86%) of 22 patients, elevation of ICP could not be prevented using moderate hypothermia. In the remaining three patients. ICP was maintained below 40 mm Hg by inducing moderate hypothermia; however, these three patients died of multiple organ failure. These results clearly indicate that moderate hypothermia induces complications more severe than those induced by mild hypothermia without improving outcomes. CONCLUSIONS: The authors concluded that moderate hypothermia is not effective in improving clinical outcomes in severely head injured patients whose ICP remains higher than 40 mm Hg after treatment with mild hypothermia combined with conventional therapies.

Adolescent↗