Biomedical subjects

K Okajima

Publications and source records attributed to K Okajima.

At least 127 records · Page 7Linked to original sources

PubMed1996

Significance of proliferating cell nuclear antigen (PCNA) expression in gastric cancer in relation to lymph node metastasis.

Proliferating cell nuclear antigen (PCNA) in gastric cancer was evaluated in relation to lymph node metastasis. A total of 125 gastric cancer patients who underwent gastrectomy were studied immunohistochemically. The PCNA-positive rate of the primary lesion with lymph node metastasis (47.6%) was significantly higher than those in those without metastasis (24.3%, P < 0.0001). The PCNA-positive rate of early gastric cancer was significantly higher in lesions with lymph node metastasis (36.9%) than in lesions without lymph node metastasis (14.7%). However, there was no significant difference between lesions with and without lymph node metastasis in advanced gastric cancer. In addition, the PCNA-positive rate in metastatic lesions (44.6%) was significantly higher than that in the primary lesion (40.0%, P = 0.001). It is concluded that gastric cancer with higher tumor growth activity has a higher rate of lymph node metastasis. Cancer cells in the metastatic foci of lymph node have a higher proliferating activity than that in the primary lesion.

Female↗

PubMed1996

Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver.

We investigated whether anticoagulation would diminish ischemia-reperfusion injury of the liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. Anticoagulant was injected intravenously 10 min before occlusion. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, reaching a peak at 6 hr, then decreasing gradually to control levels by 24 hr. CINC levels in rats pretreated with heparin (50 units/kg), AT-III (250 units/kg), or DEGR-Xa (10 mg/kg) peaked at 3 hr after reperfusion and declined to baseline within 12 hr; peak CINC values were significantly lower than in untreated control rats. Expression of CINC mRNA in liver tissue paralleled the CINC serum levels. Both myeloperoxidase activity and the number of neutrophils in the liver were decreased in the anticoagulant groups. In addition, significant correlations were observed between the maximum values of AST, ALT, and LDH versus the peak CINC levels following ischemia-reperfusion. These results indicate that the release of CINC after ischemia-reperfusion of the liver is mediated by activation of coagulation within the hepatic microcirculation.

Amino Acid Chloromethyl Ketones↗

PubMed1996

Protective effects of antithrombin III supplementation on warm ischemia and reperfusion injury in rat liver.

The effect of antithrombin III (AT III) supplementation on energy status, microcirculation, cytoprotection, and prostacyclin (PGI2) production during and after a period of warm ischemia of the rat liver was investigated. AT III supplementation (250 units/kg) stimulate prostaglandin I2 (PGI2) production from 1 hour after administration, with maximal production observed at 3 hours. Ischemia was induced by occluding the hepatoduodenal ligament for 30 minutes, and experiments were continued for 60 minutes after reperfusion. The rats received AT III (250 units/kg IC) 30 minutes before induction of liver ischemia (AT III group). In the AT III group, recovery of the beta-ATP/inorganic phosphate ratio measured by 31P nuclear magnetic resonance showed significant improvement (p < 0.01), and the recovery of tissue blood flow markedly improved (p < 0.01) compared to the saline-treated group (control group). Leakages of aspartame aminotransferase, alanine aminotransferase, and lactate dehydrogenase were mitigated in the AT III group (p < 0. 05). Ultrastructural alterations of sinusoidal endothelial cells were markedly reduced in the AT III group. The PGI2 level at the end of reperfusion was significantly elevated (p < 0.01) in the AT III group compared to the control group. The results of this study indicated that pretreatment with AT III significantly improved the energy status and microcirculation, as well as histologic damage, after liver ischemia and reperfusion. One of the fundamental effects of AT III might be mediated through the production of prostacyclin.

6-Ketoprostaglandin F1 alpha↗

PubMed1996

Radiation therapy for T1,2 glottic carcinoma: impact of overall treatment time on local control.

PURPOSE: Local control probabilities of T1,2 glottic laryngeal cancer were evaluated in relation to dose and fractionation of radiation therapy (RT). MATERIALS AND METHODS: Between 1975 and 1993, 96 T1N0M0 glottic cancers and 32 T2N0M0 glottic cancers were treated with definitive RT. Total RT dose was 60-66 Gy/2 Gy for most of the T1 and T2 tumors, although 10 T2 tumors were treated with hyperfractionation (72-74.4 Gy/1.2 Gy bid). Of the 128 patients, 90 T1 glottic tumors and 30 T2 glottic tumors were followed for > 2 years after treatment. Multivariate analyses using the Cox proportional hazards model and a logistic regression analysis were performed to evaluate the significance of prognostic variables on local control. RESULTS: The 5-year local control probability for T1 tumors was 85%, whereas that for T2 tumors was 71%. Multivariate analyses demonstrated that only overall treatment time (OTT) was a significant variable for local control. Total RT dose, normalized total doses at a fraction size of 2 Gy, and fraction size were not significant. Local control probability of T1 tumors with an OTT of 42-49 days was significantly higher than that of tumors with an OTT of > 49 days (P < 0.02). Only a 1-week interruption of RT, due to holidays, significantly reduced the 5-year local control probability of T1 glottic tumors from 89 to 74% (P < 0.05). CONCLUSIONS: These results indicate that OTT is a significant prognostic factor for local control of T1 glottic tumors.

Adult↗

PubMed1996

Association between preoperative plasma CEA levels and the prognosis of gastric cancer following curative resection. Tumor Marker Committee, Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo, Japan.

A large-scale retrospective study was undertaken to evaluate the association between preoperative plasma carcinoembryonic antigen (CEA) levels and the prognosis of 2768 gastric cancer patients who underwent curative gastrectomy between 1983 and 1984 at 66 leading medical institutions in Japan Postoperative follow-up was at least 5 years. Preoperative plasma CEA levels were also analysed against other prognostic factors. Preoperative plasma CEA levels showed strong correlations to the degree of lymph node metastasis (P < 0.001), TNM stage (P = 0.004) and the histopathology of the gastric cancer (P < 0.001). Preoperative CEA levels were also evaluated against survival, after being adjusted for the effect of clinically important factors by multivariate analysis. Patients with lower preoperative plasma CEA levels survived significantly longer than patients with higher CEA levels (P = 0.0001). This analysis demonstrates that curatively resected gastric cancer patients with higher preoperative plasma CEA levels have a poorer prognosis than those with lower levels, despite the adjustment for the effects of major prognostic factors.

Adolescent↗

PubMed1996

Role of granulocyte elastase in the formation of hemorrhagic shock-induced gastric mucosal lesions in the rat.

OBJECTIVE: To investigate the mechanism by which activated leukocytes induce gastric mucosal lesions, we examined whether granulocyte elastase is involved in the formation of such lesions in a rat model of hemorrhagic shock. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory at a university medical center. SUBJECTS: Male Wistar rats, weighing 220 to 280 g. INTERVENTIONS: Animals were subjected to hemorrhagic shock by phlebotomy. ONO-5046, a granulocyte elastase inhibitor (300 mg/kg ip), was administered 30 mins before or after phlebotomy. The effects of antithrombotic substances and tranexamic acid on hemorrhagic shock-induced gastric mucosal lesions also were examined. The effects of granulocyte elastase on the thrombomodulin activity and 35S-glycosaminoglycan content of endothelial cells were examined, using cultured human umbilical vein endothelial cells.

Animals↗

PubMed1996

Gabexate mesilate, a synthetic protease inhibitor, attenuates endotoxin-induced pulmonary vascular injury by inhibiting tumor necrosis factor production by monocytes.

OBJECTIVE: In order to determine whether gabexate mesilate, a synthetic protease inhibitor with anticoagulant properties, is useful for the treatment of adult respiratory distress syndrome, we examined its effect on endotoxin-induced pulmonary vascular injury in rats. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory at a university medical center. SUBJECTS: Male Wistar rats (180 to 220 g.) INTERVENTIONS: Animals received intravenous infusions of endotoxin (5 mg/kg iv) or saline (control). Pulmonary vascular injury was assessed 6 hrs after administration of endotoxin in terms of the increase in vascular permeability. Rats received gabexate mesilate (10 mg/kg ip), heparin, antithrombin III, an inactive derivative of activated factor X (a selective inhibitor of thrombin generation), or N-[2-[4-(2,2-dimethyl-propionyloxy) phenylsulfonylamino] benzoyl] aminoacetic acid (ONO-5046) (a potent granulocyte elastase inhibitor) 30 mins before endotoxin administration. Leukocytopenia was induced by administration of methotrexate. The effects of the gabexate mesilate on the function of activated neutrophils and the production of tumor necrosis factor -alpha (TNF-alpha) by endotoxin-stimulated monocytes were examined in vitro using neutrophils and monocytes prepared from healthy human volunteers. MEASUREMENTS AND MAIN RESULTS: Pulmonary vascular permeability was determined by measuring the vascular leakage of intravenously administered 125I-labeled bovine serum albumin. Intravenous administration of endotoxin significantly increased pulmonary vascular permeability. Gabexate mesilate significantly inhibited pulmonary vascular injury observed 6 hrs after the administration of endotoxin. Pulmonary vascular injury was not attenuated by the administration of heparin, heparin plus antithrombin III, or the inactive derivative of activated factor X, but pulmonary vascular injury was significantly attenuated in animals with methotrexate-induced leukocytopenia and in those animals treated with N-[2-[4-(2,2-dimethyl-propionyloxy) phenylsulfonylamino] benzoyl] aminoacetic acid. Gabexate mesilate in concentrations of 10(-4) to 10(-3) M inhibited the release of granulocyte elastase and leukocyte aggregation stimulated by N-formyl-methionyl-leucyl-phenylalanine and the opsonized zymosan-activated production of superoxide radical by neutrophils in vitro. Gabexate mesilate significantly inhibited the endotoxin-induced increase in the serum concentration of TNF-alpha in vivo and, at a concentration of 10(-8) M, the production of TNF-alpha by endotoxin-stimulated monocytes in vitro. CONCLUSION: Our findings suggest that gabexate mesilate attenuated endotoxin-induced pulmonary vascular injury mainly by inhibiting TNF-alpha production by monocytes, which may play a central role in sepsis-related lung injury.

Animals↗

PubMed1996

Role of granulocyte elastase in ischemia/reperfusion injury of rat liver.

OBJECTIVE: To investigate the role of granulocyte elastase in ischemia/reperfusion injury of liver, the effect of ONO-5046, a granulocyte elastase inhibitor, was examined in ischemia/reperfusion-induced liver injury in rats. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory at a university medical center. SUBJECTS: Male Wistar rats, weighing 220 to 280 g. INTERVENTIONS: Animals receiving continuous intravenous infusion of ONO-5046 (50 mg/kg/hr) were subjected to hepatic ischemia/reperfusion. Hepatic damage was evaluated by effects on bile formation capacity, plasma clearance of indocyanine green, and serum aminotransferase concentrations after ischemia/reperfusion. MEASUREMENTS AND MAIN RESULTS: Hepatic dysfunction, observed after 60 mins of ischemia/reperfusion, led to a reduction in bile flow and to a decrease in the plasma clearance of indocyanine green. These indicators of hepatic dysfunction were prevented, to a large extent, by administration of ONO-5046. Serum concentrations of aminotransferases increased after hepatic ischemia/reperfusion, peaking at 12 hrs of reperfusion. Increases in serum concentrations of aminotransferases were significantly inhibited by ONO-5046. CONCLUSION: Granulocyte elastase derived from activated leukocytes may play a critical role in hepatic dysfunction and the subsequent hepatic injury induced by ischemia/reperfusion.

Animals↗

PubMed1996

Soluble intercellular adhesion molecule-1 and soluble E-selectin levels in patients with atopic dermatitis.

The serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) were determined by double determinant immunoassay (DDIA), in 37 patients with atopic dermatitis (AD) and 31 age- and sex-matched healthy control subjects. Both sICAM-1 and sE-selectin levels were significantly higher in patients with AD than in healthy controls (P < 0.01), and were correlated with disease severity. A longitudinal study of patients with AD revealed that the levels of sICAM-1 decreased in those in whom symptoms improved. The sICAM-1 levels were significantly correlated with those of sE-selectin. Our studies suggest that such high levels of serum sICAM-1 and sE-selectin may affect the immune response in patients with AD. The levels of sICAM-1 and sE-selectin may be a useful immunological parameter for monitoring disease activity in AD.

Adolescent↗

PubMed1996

Development of an MR simulator: experimental verification of geometric distortion and clinical application.

PURPOSE: To evaluate the geometric distortion on magnetic resonance (MR) images obtained with a permanent magnet system and determine the usefulness of MR imaging-assisted x-ray simulation in radiation therapy treatment planning (RTTP). MATERIALS AND METHODS: The authors measured the distortion on MR images of grid-pattern phantoms. MR imaging-assisted x-ray simulation was performed with skin markers in 14 patients with bone tumors. Treatment planning had already been performed with a conventional system. RESULTS: On phantom images, most of the positional displacements within a 120-mm radius from the center of the static magnetic field were less than 2 mm; larger displacements were observed in the peripheral region of the images. MR imaging was useful in the RTTP of all patients. The original radiation field was modified after MR examination in six patients. CONCLUSION: The amount of image distortion within the practical area is acceptable for RTTP. MR imaging-assisted x-ray simulation is useful for patients with bone tumors and warrants further investigation.

Aged↗

PubMed1996

Attenuation of endotoxin-induced pulmonary vascular injury by antithrombin III.

We evaluated the effects of antithrombin III (AT III) on the pulmonary vascular injury induced by injecting rats with lipopolysaccharide (LPS) to investigate the possible usefulness of AT III as a treatment for acute respiratory distress syndrome. The intravenous administration of AT III prevented the pulmonary accumulation of leukocytes (as evaluated by myeloperoxidase activity) and the increase in pulmonary vascular permeability to 125I-bovine serum albumin induced by LPS. The increase in pulmonary vascular permeability induced by LPS administration was unaffected by various anticoagulants but was inhibited by the leukocytopenia induced by nitrogen mustard or by the administration of a granulocyte elastase inhibitor, ONO-5046. AT III given alone, but not heparin plus AT III or Trp49-modified AT III, which lacks affinity for heparin, significantly increased the plasma concentration of 6-keto-prostaglandin F1alpha, suggesting that the interaction of AT III with heparin-like substances at the endothelial cell surface promotes the release of prostacyclin from endothelial cells in vivo. Trp49-modified AT III failed to prevent the LPS-induced accumulation of leukocytes and vascular injury. The pulmonary accumulation of leukocytes and vascular injury induced by LPS were not prevented by administering AT III to rats that were pretreated with indomethacin. The continuous intravenous infusion of prostacyclin prevented the LPS-induced pulmonary accumulation of leukocytes and vascular injury. Findings suggest that AT III depends on its ability to promote the release of prostacyclin, a potent inhibitor of leukocyte activation, from endothelial cells to prevent pulmonary vascular injury induced by LPS.

6-Ketoprostaglandin F1 alpha↗

PubMed1996

Recombinant thrombomodulin prevents endotoxin-induced lung injury in rats by inhibiting leukocyte activation.

Acute respiratory distress syndrome (ARDS) is a serious complication of sepsis. Thrombomodulin, an important endothelial anticoagulant, binds thrombin to generate activated protein C (APC). We have previously demonstrated that APC prevents endotoxin (ET)-induced pulmonary vascular injury by inhibiting activated leukocytes. We therefore examined whether recombinant human soluble thrombomodulin (rhs-TM) prevents activated leukocyte-induced pulmonary vascular injury in rats receiving ET. Intravenous administration of rhs-TM prevented ET-induced pulmonary accumulation of leukocytes and increase in pulmonary vascular permeability, as well as ET-induced histological changes, such as leukocyte infiltration and pulmonary interstitial edema. Dansyl-Glu-Gly-Arg-chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, did not prevent these effects of ET. rhs-TM did not prevent ET-induced pulmonary accumulation of leukocytes and pulmonary vascular injury in rats pretreated with DEGR-Xa. These results suggest that rhs-TM prevents ET-induced pulmonary vascular injury by inhibiting pulmonary accumulation of leukocytes and that this effect may be mediated primarily by APC generation.

Animals↗

PubMed1996

[Measurement of the plasma transforming growth factor-beta 1 (TGF-beta 1) level in patients of gastric carcinoma--compared with the serum IAP level and the lymphocyte subsets (CD3, CD4, CD8)].

We evaluated the clinical significance of the plasma TGF-beta 1 by enzyme-linked immunosorbent assay (ELISA) in 40 patients with gastric carcinoma before operation who were hospitalized at our department between August 1992 and March 1993. Moreover, we examined the correlation of the immunosuppressive acidic protein (IAP) in the serum with the plasma TGF-beta 1 level. The lymphocyte subsets were analyzed with monoclonal antibodies (CD3, CD4, CD8) and compared with the plasma TGF-beta 1 level. Results 1) The plasma TGF-beta 1 was significantly high in patients with advanced stage of gastric carcinoma (with respect to the depth invasion) and poorly differentiated adenocarcinoma (histological type) (p < 0.01). When the carcinoma was macroscopically found to be advanced, TGF-beta 1 was higher in the invasive type than in the noninvasive type (p < 0.05). 2) We found a significant correlation between the plasma TGF-beta 1 and IAP in the serum (n = 25, r = 0.677, p < 0.01). 3) The lymphocyte fraction of CD3, CD4 was decreased in patients with a high level of TGF-beta 1, and was related with the plasma TGF-beta 1 level. Thus, TGF-beta 1 was presumed to be deeply associated with in the growth and progression of gastric carcinoma and related to systemic immunosuppressive reaction.

CD3 Complex↗

PubMed1996

Postoperative evaluation of pylorus-preserving gastrectomy for early gastric cancer.

Physical results after pylorus-preserving gastrectomy (PPG) with preservation of the vagus nerve were evaluated. The status of 15 patients with early gastric cancer after PPG was compared with that of 14 patients after distal gastrectomy (DG). The postoperative/preoperative body-weight ratio of the PPG group (0.99) was significantly greater than that of the DG group (0.92). Patients who had PPG had fewer postoperative abdominal symptoms than those who underwent DG. The gastric emptying pattern of patients who had a pylorus-preserving procedure was slower than that of those who had conventional gastrectomy, and more similar to the preoperative pattern. Contraction of the gallbladder after PPG was better than after DG. Gastroscopy revealed that the mucosa of the stomach remnant after PPG was less abnormal than after DG. In conclusion, PPG is a more physiological operation than conventional DG and should be applied in carefully selected cases of early gastric cancer.

Body Weight↗

PubMed1996

A novel platelet activating factor antagonist, SM-12502, attenuates endotoxin-induced disseminated intravascular coagulation and acute pulmonary vascular injury by inhibiting TNF production in rats.

Adult respiratory distress syndrome and disseminated intravascular coagulation are important pathologic conditions affecting the outcome of patients with sepsis. To elucidate the possible therapeutic efficacy of SM-12502, a novel platelet activating factor antagonist, on acute lung injury and disseminated intravascular coagulation in sepsis, we investigated the effect of SM-12502 on an endotoxin (ET)-induced septic model in rats. SM-12502 prevented ET-induced increases in pulmonary vascular permeability and ET-induced histologic changes, such as leukocyte infiltration and pulmonary interstitial edema, 6 h following the administration of ET (5 mg/kg). SM-12502 also inhibited the decrease in fibrinogen and the increase in fibrin and fibrinogen degradation products observed following ET administration. SM-12502 prevented increases in the serum concentration of tumor necrosis factor (TNF) 90 min following ET administration in vivo, and significantly inhibited the production of TNF-alpha by ET-stimulated monocytes in vitro. These findings suggest that SM-12502 attenuates the actions of endotoxin by the inhibition of TNF production.

Animals↗

PubMed1996

[Preoperative diagnosis and surgical treatment for lymph node metastasis in gastric cancer].

In order to clarify the preoperative diagnostic ability for lymph node metastasis, images from magnetic resonance imaging (MRI), computed axial tomography (CT) and ultrasonography (US) were evaluated in 200 gastric cancer patients. The long-term results of 2,000 gastric cancer patients who had undergone gastrectomy were also studied to evaluate the effectiveness of lymphadenectomy. 1) Preoperative diagnosis of lymph node metastasis: The detection rate of lymph nodes around the stomach was 34.1% in MRI, 18.7% in CT and 5.0% in US. The incidence of metastasis was over 80% when the size of lymph node imaged was 1.5 cm and over, against 25% for lymph nodes less than 1.0 cm in size. The detection rate of metastatic lymph node according to the mode of metastasis was 88% for macro-nodular type, 66% for micro-nodular type, 57% for diffuse type in MRI, 70, 41 and 15% in CT, and 38, 3, 0% in US, respectively. Therefore, MRI was most useful for detecting metastatic lymph node preoperatively. 2) Long-term results of gastric cancer with lymph node metastasis: The cumulative 5-year survival rate was 84.2% in n0, 56.1% in n1, 33.7% in n2, 16.5% in n3, and 5.1% in n4 patients. Satisfactory long-term results were obtained for n2 or less patients without serosal invasion. Moreover, by paraaortic lymph node dissection, the cumulative 5-year survival rate in n4 patients was 16.4% (27.8% for cases with radical resection). These results showed the effectiveness of lymph node dissection for gastric cancer.

Follow-Up Studies↗

PubMed1995

Effects of antithrombin III (AT III) and Trp49-modified AT III on plasma level of 6-keto-PGF1 alpha in rats.

We evaluated the effect of antithrombin III (AT III) on the plasma level of 6-keto-PGF1 alpha in rats to determine whether AT III may promote the release of prostacyclin (PGl2) from endothelial cells in vivo. The intravenous administration of AT III (250 U/kg) significantly increased the plasma levels of 6-keto-PGF1 alpha, with a peak seen 90 min post-administration. Neither Trp49-modified AT III, which lacks affinity for heparin but retains an inhibitory capacity for thrombin, nor heparin plus AT III, increased the plasma level of 6-keto-PGF1 alpha 90 min after administration. Indomethacin pretreatment inhibited the increase in plasma levels of 6-keto-PGF1 alpha produced by AT III. Observations suggest that AT III may promote the release of PGl2 from endothelial cells by interacting with heparin-like glycosaminoglycans in vivo, consistent with previous observations in cultured endothelial cells.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Endotoxin-induced pulmonary vascular injury is mainly mediated by activated neutrophils in rats.

Acute respiratory failure is a common complication in patients with disseminated intravascular coagulation associated with sepsis. To elucidate the role of coagulation abnormalities in acute lung injury in sepsis, we investigated the effect of anticoagulants on the pulmonary vascular injury in rat induced by lipopolysaccharide (LPS). When administered intravenously, LPS (5 mg/kg body weight) significantly increased the accumulation of 111indium-labeled neutrophils in lung 30 min after administration. Subsequently, the pulmonary vascular permeability and the serum level of fibrin and fibrinogen degradation products (E) [FDP (E)] increased and remained elevated for several hours. Neither heparin alone, heparin plus antithrombin III, or dansyl-Glu-Gly-Arg-chloromethyl ketone-treated factor Xa, a selective inhibitor of thrombin generation, prevented LPS-induced vascular injury 6 hours after LPS administration, whereas these substances significantly inhibited the increase in serum FDP (E) at that time. LPS-induced pulmonary vascular injury was significantly attenuated in rats with methotrexate-induced leukocytopenia or treated with ONO-5046, a potent granulocyte elastase inhibitor, although ONO-5046 did not inhibit the LPS-induced increase in serum FDP (E). Thus, activated leukocytes play a more important role than coagulation abnormalities in the pathogenesis of LPS-induced pulmonary vascular injury in an experimental rat model of endotoxemia.

Amino Acid Chloromethyl Ketones↗