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M Sekiguchi

Publications and source records attributed to M Sekiguchi.

766 records · Page 43Linked to original sources
PubMedDate not supplied

Eosinophil active cytokines and surface analysis of eosinophils in Churg-Strauss syndrome.

There are few reports regarding the measurement of cytokines and surface analysis of eosinophils in Churg-Strauss syndrome (CSS). To examine the pathophysiology of CSS, concentrations of cytokines in serum and bronchoalveolar lavage fluid (BALF), and surface antigens on peripheral blood eosinophils were analyzed in five patients with CSS. Concentrations of cytokines (interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-3 (IL-3), interleukin-5 (IL-5) and granulocyte/macrophage colony stimulating factor (GM-CSF) were measured using ELISA. Surface antigens on eosinophils in peripheral blood were analyzed using flow cytometry. A concentration of interleukin-5 (IL-5) and TNF-alpha in serum was detected in five cases; however IL-1 beta, GM-CSF, and IL-3 were detected in 3 of 5, 2 of 5, and 1 of 5 patients, respectively. In BALF, TNF-alpha and IL-5 were detected in 2 of 3 and 1 of 3 patients, respectively; however, neither IL-1 beta, GM-CSF, nor IL-3 was detected in any. Newly expressed surface antigens such as CD25, CD4, and CD69 were observed on peripheral blood eosinophils in five cases. CD54 and HLA-DR were expressed in 4 of 5 and 3 of 5 patients, respectively. Eosinophils in peripheral blood are activated to various degrees, possibly depending on cytokine stimulation. This eosinophil activation may be related to the clinical stage of CSS.

Adult↗
PubMedDate not supplied

Specific neutrophil elastase inhibitor does not attenuate acute lung injury induced by air embolism in awake sheep.

To investigate the role played by neutrophil-derived elastase in acute lung injury, this study examined the effects of treatment of ONO-5046, a competitive, reversible, and specific neutrophil elastase inhibitor, on lung dysfunction induced by air emboli in awake sheep. Sheep were prepared with chronic lung lymph fistula. In experiment 1, air (1.23 mL/min) was infused over a 2-h period into the pulmonary artery and hemodynamic monitoring was performed over a 5-h period. In experiment 2, air was infused in the same manner as in experiment 1, 1 h after the continuous infusion of ONO-5046 (10 mg/kg h-1) had begun. In experiment 1, pulmonary artery pressure (Ppa) increased from the baseline value of 17.0 +/- 0.7 cm H2O to 28.3 +/- 1.8 1 h after the beginning of the air infusion. Ppa returned to the baseline values within 1 h after the air infusion was stopped. Lung lymph flow (Qlym) increased from the baseline value of 3.7 +/- 0.7 mL/0.5 h to 8.5 +/- 1.9 after 1 h of air infusion. After the air infusion was stopped, Qlym continued to increase. When sheep were treated with ONO-5046, Ppa and Qlym increased in a fashion similar to that in the experiment 1. These findings suggest that ONO-5046 does not attenuate air embolism-induced lung injury and that neutrophil-derived elastase may not play an important role in air embolism-induced lung injury in awake sheep.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Neutrophils pretreated with granulocyte colony-stimulating factor (G-CSF) are not related to the severity of endotoxin-induced lung injury.

Neutrophils play an important role in mediating acute lung injury that is characteristic of adult respiratory distress syndrome. Granulocyte colony-stimulating factor (G-CSF) has been shown to increase neutrophil counts and to enhance their biological functions. This study investigated the effects of neutrophils pretreated with G-CSF on endotoxin-induced lung injury in conscious sheep. Nineteen sheep were chronically instrumented with a lung lymph fistula and vascular catheters for monitoring. Sheep were randomly allocated into three groups: group 1-sheep were infused only with endotoxin; group 2-G-CSF (250 micrograms/day) was administered intravenously for 5 days prior to endotoxin; and group 3-G-CSF (125 micrograms) was administered just before endotoxin. In each group, sheep received E. coli endotoxin (1 microgram/kg) for 30 min and observations were made for 5 h after endotoxin administration. Circulating leukocyte counts before endotoxin markedly increased in group 2 and significantly decreased in group 3, when compared with the level in group 1 (9700 +/- 900 (SEM) in group 1, 49,900 +/- 10,000 in group 2, and 3600 +/- 600/microL in group 3). In each group, circulating leukocyte counts significantly decreased 1 h after endotoxin administration and then returned to baseline values. However, there were no significant differences in either pulmonary hemodynamic or lung lymph responses to endotoxin among the groups. The results indicate that G-CSF does not adversely affect physiologic responses of the lung to endotoxin in sheep.

Animals↗
PubMedDate not supplied

Effect of post-treatment with granulocyte colony-stimulating factor on endotoxin-induced lung injury in sheep.

We administered a bolus of G-CSF (250 micrograms/body) just after the infusion of endotoxin (1 microgram/kg) in awake sheep with chronic lung lymph fistula to examine the effect of post-treatment with G-CSF on endotoxin-induced lung injury. We measured pulmonary hemodynamics, lung lymph flow, and concentrations of thromboxane B2 and 6-keto-prostaglandin F1 alpha in plasma and lung lymph. In the G-CSF post-treated group, the pulmonary arterial pressure, pulmonary vascular resistance, and lung lymph flow did not significantly increase in the late period (3-5 h after endotoxin infusion). The arterial oxygen gas tension in the late period was higher in the G-CSF post-treated sheep than in those that received only endotoxin. Although the level of thromboxane B2 in plasma significantly increased at 1 h after endotoxin, the lung lymph flow did not increase much in the G-CSF post-treated group. We conclude that post-treatment with G-CSF instead attenuates the degree of pulmonary vascular leakage on endotoxin-induced lung injury and increased thromboxane B2, the principle metabolite of thromboxane A2, may not exacerbate the injury in awake sheep.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Electrophysiologic assessment of the transplanted canine heart: correspondence to histopathologic findings in acute rejection.

This study was undertaken to electrophysiologically find signs of rejection after heart transplantation. A donor heart with a created atrial septal defect was implanted in the retroperitoneal space by anastomosing the thoracic aorta and left pulmonary artery of the donor heart to the abdominal aorta and inferior vena cava of the recipient heart, respectively. Endocardial leads were set up in the right atrium in the vicinity of the bundle of His and in the right ventricle. Cyclosporine (10 to 18 mg/kg/day, continuously) and prednisolone (1.0 mg/kg/day, for the first 4 days) were given orally. Electrophysiologic examinations were performed 1 to 4 days (control data) after the transplantation and were compared with data obtained 5 to 21 days after operation on 12 mongrel dogs. Finally, histopathology of the donor heart was studied. Results showed that the effective refractory period (ERP) of the atrioventricular conduction system was prolonged in six animals from 120 +/- 25 to 192 +/- 35 msec (p less than 0.02) on average. The ERP of the ventricle was shortened in four dogs from 153 +/- 36 to 123 +/- 17 msec (p less than 0.05). Specimens disclosed mononuclear cell infiltration in the atrioventricular node, the bundle of His, and the right and left bundle branches in eight of 12 cases and mild to moderate myocyte damage with cell infiltration in the ventricular septum of the same eight hearts. The ERP of the atrioventricular conduction system showed no change in four cases without mononuclear cell infiltration in the conduction system. These results suggested the feasibility of electrophysiologic monitoring as a means for detecting acute rejection in the prenecrotic stage in transplanted hearts.

Acute Disease↗
PubMedDate not supplied

BK virus-induced osteosarcoma (Os515) as a model of human osteosarcoma.

BK virus was isolated by Gardner et al in 1971 from the urine of an immunosuppressed patient with a kidney allograft. Antibodies to this virus are ubiquitous in the general populations worldwide, but the oncogenic capacity of BKV in humans had not been reported. The virus transformed in vitro permissive human and non-permissive animal cells, and the transformed cells had the T antigen. Intracerebral and intravenous inoculation of BKV in newborn hamsters induced malignant tumours (mainly ependymomas, malignant insulinomas, and osteosarcomas). Subcutaneous and intraperitoneal routes were also effective. The virus was only rescued from a few tumours by fusion with human embryonic cells or Vero cells. Brain tumours appeared earlier and osteosarcomas developed in animals which survived for more than 6 months. Many of the osteosarcomas were bony and grew slowly with frequent lung metastases, and a few osteosarcomas were soft and grew rapidly without lung metastases. Experimental targeting chemotherapy with doxorubicin (DX)-containing immunoliposomes was performed against Os515 osteosarcoma. In in vitro experiments, DX-Lip-MoAb29 showed a more significant inhibitory effect on cultured Os515 cells than free Dx and DX-Lip. DX-Lip DNP had less effect. In in vivo experiments, DX-Lip-MoAb29 suppressed the growth of Os515 tumour isografts in hamsters and prolonged the survival of recipients more significantly than free DX.

Animals↗