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Biomedical subjects

K Okabe

Publications and source records attributed to K Okabe.

At least 73 records · Page 4Linked to original sources
PubMed1998

Xanthine oxidase inhibition attenuates kupffer cell production of neutrophil chemoattractant following ischemia-reperfusion in rat liver.

We investigated the effects of the xanthine oxidase inhibitor, BOF-4272, on the production of cytokine-induced neutrophil chemoattractant (CINC) following reperfusion injury in rat liver. Ischemia was induced for 30 minutes by portal vein occlusion. Animals were pretreated with intravenous injection of BOF-4272 (1 mg/kg) or heparin (50 U/kg) 5 minutes before vascular clamp. Both BOF-4272 and heparin limited increases in the chemoattractant compared with nonpretreated rats. Pretreatment with BOF-4272 plus heparin resulted in an additive effect. Most cells immunostained for chemoattractant were macrophages in sinusoids. In vitro chemoattractant production by Kupffer cells isolated from animals pretreated with heparin or BOF-4272 was significantly lower than by Kupffer cells from nonpretreated animals. Expression of transcripts in liver for chemoattractant peaked 3 hours after reperfusion in nonpretreated animals, while pretreatment with heparin or BOF-4272 significantly decreased chemoattractant mRNA levels. In vitro chemoattractant transcription and production could be induced in naive Kupffer cells by hypoxanthine and xanthine oxidase, but BOF-4272 prevented these increases. We conclude that Kupffer cells release chemoattractant in response to oxygen radicals reducible by xanthine oxidase inhibition.

Animals↗
PubMed1998

A novel strategy for introducing exogenous bcl-2 into neuronal cells: the Cre/loxP system-mediated activation of bcl-2 for preventing programmed cell death using recombinant adenoviruses.

We have established a novel strategy for introducing exogenous Bcl-2 into neuronal cells that is mediated by Cre/loxP recombination using recombinant adenoviral vectors. An on/off-switching cassette for Bcl-2 (CALNLbcl-2) was designed to express Bcl-2 by recombinase Cre-mediated excisional deletion of a spacer DNA flanked by a pair of loxP sites. Exogenous Bcl-2 was clearly induced in PC12 cell lines carrying CALNLbcl-2 after infection with recombinant adenovirus producing recombinase Cre (AxCANCre). Dual infection with both AxCANCre and a recombinant adenovirus bearing CALNLbcl-2 showed efficient delivery of exogenous Bcl-2 into a hybrid motoneuronal cell line and primary chicken spinal motoneurons. The delivery of foreign Bcl-2 promoted survival of motoneurons in medium either containing or lacking trophic support. Thus, this strategy for delivery of exogenous Bcl-2 will be useful for studying neuronal death as well as for introducing foreign genes into postmitotic neurons under the control of recombinase Cre.

Adenoviridae↗
PubMed1998

Experimental study of tracheal allotransplantation with cryopreserved grafts.

OBJECTIVE: Tracheal reconstruction is necessary in patients with extensive tracheal stenosis caused by neoplasm, trauma, and congenital disease. We investigated the possibility of tracheal allotransplantation with cryopreserved grafts in a canine model. METHODS: A seven-ring section of thoracic trachea was removed in 19 adult mongrel dogs. In group A (n = 4), a five-ring tracheal autograft was implanted. In group B (n = 6), a five-ring allograft was implanted without immunosuppression. In group C (n = 9), a five-ring cryopreserved tracheal allograft was implanted without immunosuppression. Omentopexy wrapping around the grafts and both anastomotic sites was used in all animals. RESULTS: All grafts survived without any evidence of atrophy or stenosis in group A. All animals in group B died of severe airway obstruction within 1 month, and postmortem examination of these grafts showed epithelial defect and necrotic tracheal cartilage in the scar tissue. In group C, no animals died of asphyxia caused by severe stenosis of the grafts. The graft epithelium was no longer present 20 days after transplantation, and the graft was covered with regenerated epithelium within about 60 days after the operation. CONCLUSION: These findings show that cryopreserved tracheal allografts can be transplanted by means of omentopexy without immunosuppression and that cryopreservation may reduce tracheal allogenicity.

Animals↗
PubMed1998

Response-oriented individualized induction therapy followed by intensive consolidation and maintenance for adult patients with acute lymphoblastic leukemia: the ALL-87 study of the Japan Adult Leukemia Study Group (JALSG).

The Japan Adult Leukemia Study Group conducted the ALL-87 study to determine whether response-oriented induction therapy and intensive consolidation and maintenance/intensification therapies could increase complete remission (CR) rate and survival in adult acute lymphoblastic leukemia (ALL). Of 121 patients registered, 116 were evaluated. Patients' ages ranged from 15 to 72 years (median, 38 years). Induction therapy, which consisted of doxorubicin, vincristine, cyclophosphamide, L-asparaginase and prednisolone, was given in a response-oriented individualized fashion. Patients were randomly allocated either to receive or not, intrathecal chemotherapy on day 8 of the induction therapy. Complete remission (CR) was obtained in 97 (83.6%) patients (90.2%) in patients of less than 50 years of age and 67.6% in patients 50 years of age or older). At a median follow-up period of 65 months, the predicted 6-year overall survival and event free survival (EFS) rates of 116 patients were 23.4 and 20.0%, respectively. Predicted 6-year survival and disease-free survival (DFS) rates of 97 CR patients were 28.2 and 24.5%, respectively. By multivariate analysis, patients under 40 years of age (P = 0.002) or those with a platelet count of more than 100,000/microliters (P = 0.004) were significant favorable prognostic factors for obtaining CR, and days to CR less than 50 (P = 0.003), patients under 50 years of age (P = 0.005) were significant favorable factors for longer DFS. There was no significant difference in CR rates and DFS between the two randomized groups according to the intrathecal chemotherapy on day 8. Response-oriented induction therapy produced a high CR rate, but fairly intensive consolidation and maintenance/intensification chemotherapies resulted in only a marginal effect on DFS in adult ALL. Although age is one of the most important prognostic factors in ALL, the outcome was unsatisfactory even in younger adult patients using chemotherapeutic regimen employed in this study.

Adolescent↗
PubMed1998

Intracellular calcium affects neutrophil chemoattractant expression by macrophages in rats with cerulein-induced pancreatitis.

Pancreatitis complicated with infection often results in the development of multiple organ failure. We investigated the role of altered intracellular calcium as a priming signal for cytokine-induced neutrophil chemoattractant expression in this process. Agents modulating cytosolic Ca2+ were utilized to study the in vivo and in vitro cytokine-induced neutrophil chemoattractant expression for macrophages in rats with cerulein-induced pancreatitis after intraperitoneal administration of lipopolysaccharide as a septic challenge. Pretreatment with the calcium channel blocker verapamil significantly reduced serum cytokine-induced neutrophil chemoattractant concentrations in rats with cerulein-induced pancreatitis after septic challenge. Lipopolysaccharide-stimulated in vitro cytokine-induced neutrophil chemoattractant (CINC) production by peritoneal macrophages was significantly enhanced by pretreatment with thapsigargin (an inhibitor of the endoplasmic reticulum-resident Ca2+-ATPase), but not by A23187 (a calcium-specific ionophore, extracellular Ca2+ influx). Pretreatment with U73122 (a phospholipase C inhibitor) inhibited lipopolysaccharide-stimulated but not basal cytokine-induced neutrophil chemoattractant production, while verapamil (a calcium channel blocker), TMB-8 (an inhibitor of calcium release from endoplasmic reticulum), and W7 (calmodulin antagonist) completely abrogated the chemoattractant production. Altered intracellular calcium, due to Ca2+ efflux from intracellular stores, may be involved in the "priming" of macrophages to release cytokine-induced neutrophil chemoattractant following triggering with lipopolysaccharide during acute cerulein pancreatitis.

Acute Disease↗
PubMed1998

Immunosuppressants decrease neutrophil chemoattractant and attenuate ischemia/reperfusion injury of the liver in rats.

BACKGROUND: Neutrophils may play an important role in the development of liver ischemia/reperfusion injury. We investigated the effects of the immunosuppressants azathioprine (AZA), cyclosporine A (CsA), tacrolimus (FK506), and rapamycin (RPM) on the expression of cytokine-induced neutrophil chemoattractant (CINC) after ischemia/reperfusion of the liver. METHODS: Liver ischemia was induced in male Wistar rats by occluding the portal vein with a microvascular clip for 30 minutes. Rats received two intramuscular injections of AZA (4 mg/kg), CsA (5 mg/kg), FK506 (0.5 mg/kg), or RPM (0.5 mg/kg) 3 and 24 hours before ischemia/reperfusion of the liver. RESULTS: Serum CINC concentrations in untreated animals increased, peaked 6 hours after reperfusion, and thereafter decreased gradually. Pretreatment with AZA, CsA, FK506, and RPM, however, inhibited the increase in serum CINC concentrations after reperfusion. CINC mRNA in liver tissue increased and peaked 3 hours after reperfusion, but was significantly lower in animals treated with AZA, CsA, FK506, and RPM. In vitro CINC production by Kupffer cells harvested from animals treated with AZA, CsA, FK506, or RPM 3 hours after reperfusion was also significantly lower than that observed in untreated animals. Both myeloperoxidase activity and the number of neutrophils accumulating in the liver 24 hours after reperfusion in animals treated with AZA, CsA, FK506, and RPM were significantly lower than in untreated animals. This correlated with lower serum aspartate transaminase, alanine transaminase, and lactate dehydrogenase levels in animals treated with AZA, CsA, FK506, and RPM 24 hours after reperfusion. CONCLUSION: The immunosuppressants AZA, CsA, FK506, and RPM reduce neutrophil accumulation and attenuate ischemia/reperfusion injury of the liver.

Animals↗
PubMed1998

Arthroscopic management of temporomandibular closed lock.

Sixty-three consecutive patients with painful closed lock involving 83 temporomandibular joints were treated by surgery and followed up for at least 24 months. Prior to surgical treatment all had imaging to demonstrate that the cause of their painful jaw locking was an anterior displaced disc without reduction. All patients had received at least three months non-surgical treatment without response. The arthroscopic surgery consisted of release of adhesions, manipulation and placement of 25 mg hyaluronic acid into the joint space. No significant surgical complications occurred. Postoperative treatment involved physical therapy and stabilization splints. At 24 months after surgery 57 patients (90.5 per cent) had no pain and month opening had improved from preoperative 27.2 +/- 5.4 mm to 44.4 +/- 4.1 mm (p < 0.001). This study shows that arthroscopic surgery with continuing non-surgical therapy is a highly effective treatment for painful closed lock.

Adolescent↗
PubMed1998

Preparation and characterization of oil-in-water type poly (D,L-lactic acid) microspheres containing testosterone enanthate.

Poly (D,L-lactic acid) (PLA) microspheres containing testosterone enanthate (ET) were prepared by using an oil-in-water (O/W) emulsion technique. The size distribution of the microspheres obtained could be explained by a log-normal distribution, and as a result, it was found that ET fully incorporates into microspheres even when the drug is loaded at up to 50%. On the other hand, the dissolution behavior of ET from microspheres was strongly dependent on particle size, suggesting that dissolution of the drug from microspheres can be easily controlled by controlling the preparative conditions.

Calorimetry, Differential Scanning↗
PubMed1998

[Phase II study of KRN8602 (MX2) for malignant lymphoma].

We performed a clinical phase II study of KRN8602, a new anthracycline derivative, for relapsed or recurrent malignant lymphoma. KRN8602 was given at doses of 12-15 mg/m2 for 3 consecutive days, repeating every 3-4 weeks. Among 44 patients entered into the study, 36 were evaluable for safety, and 35 were evaluable for efficacy. The response rate was 18.2% (6PR/33) for non-Hodgkin's lymphoma and 0% (0/2) for Hodgkin's disease. Major toxicities were bone marrow suppression and gastrointestinal toxicity. Leukopenia was observed in 77.8%, thrombocytopenia in 44.4%, hemoglobin decrease in 44.4%, nausea and vomiting in 94.4% and anorexia in 80.6%. However, all toxicities were clinically manageable.

Anorexia↗
PubMed1998

[Clinical study on prostate cancer initially presenting with disseminated intravascular coagulation syndrome].

We experienced five patients with prostate cancer with disseminated intravascular coagulation syndrome (DIC) at the first presentation at Gunma University Hospital and affiliated institutions between 1991 and 1997. Their average age was 68 years, average DIC score at the first presentation was 10 and prostate specific antigen (PSA) level was more than 700 ng/ml. All of them had multiple bone metastases. The therapy for DIC and hormonal therapy for prostate cancer were simultaneously started at the first presentation before prostate needle biopsy, but all patients died. The average number of days from the start of DIC to death was 685 days. The patients initially showed a good response to therapy, but their conditions soon aggravated. The prognosis was extremely poor, but some proper therapies lead to the prognosis which was equal to that of prostate cancer in Stage D2 without DIC.

Adenocarcinoma↗
PubMed1998

[A case report of dumbbell neurogenic tumor of the superior mediastinum].

A 15-year-old female was admitted because of the superior mediastinum mass on chest X-rays and sensory loss of ulnar side of the left arm. Computed tomographic scanning and magnetic resonance imaging revealed that the tumor was dumbbell-shaped and invaded the vertebral canal through the intervertebral foramen between C 7 and Th 1. At first laminectomy of vertebrae (C 6-Th 1) was made in a prone position and intra-spinal portion of the tumor was resected. Then the patient was placed in a supine position and the chest was opened by left hemicollar incision and sternotomy to the 2nd intercostal space. The tumor was divided into two parts at the level of 1st rib and completely removed. The pathological diagnosis was schwannoma. This procedure is safe and useful for dumbbell type tumor located in superior mediastinum, especially in case of large tumor from neck to the thoracic cavity.

Adolescent↗
PubMed1997

Oxytocin enhances action potentials in pregnant human myometrium--a study with microelectrodes.

OBJECTIVE: Our purpose was to quantitatively assess the effects of oxytocin on membrane properties in the pregnant human myometrium. STUDY DESIGN: Specimens were obtained from the lower uterine segment during cesarean section at term. Electrical activity was recorded from individual cells by a conventional microelectrode method and the membrane functions were analyzed. RESULTS: Two types of spontaneous action potentials were seen: a long plateau potential and a spike-like action potential. With no change in the resting membrane potential, low concentrations of oxytocin either evoked an action potential with a plateau phase, increased the amplitude and duration of the plateau potential, or increased the frequency of generation of action potentials. Oxytocin also lowered the threshold for evoking an action potential. Higher concentrations depolarized the membrane with an associated reduction in membrane resistance. CONCLUSION: Oxytocin augments the excitability of pregnant human myometrial cells by multiple actions on the membrane, affecting both frequency and amplitude of action potentials.

Action Potentials↗
PubMed1997

Effect of maternal lifestyle on cord blood IgE factor.

During recent decades much interest has been focused on the possibility of predicting and preventing atopic diseases during pregnancy. The idea of being able to detect a predisposition early and take suitable environmental measures in order to avoid overt allergy is an attractive position. Elevated cord IgE of around 1.0 IU/ml has been proposed as a predictor in western children. However, there remains no information about the effect of maternal lifestyle during pregnancy on these levels. Total IgE levels were therefore determined using Pharmacia CAP system and PRIST, with sensitivities of 0.01 kU/l and 0.25 kU/l, respectively, from serum samples taken from 1138 Japanese pairs of cord blood and pregnant women responding to a questionnaire regarding 17 health practices, intake of 32 food allergens and 5 environmental factors. Of these, 28 (2.5%) pairs of samples were excluded from further analysis because of high contamination of IgA (> 15.4 mg/ml) in cord blood. Median cord blood IgE was 0.286 kU/l and geometric mean IgE was 66.25 kU/l in maternal sera using CAP system; there was no significant correlation between maternal log (IgE) and cord blood IgE. Similar results were obtained from PRIST, whose correlation with CAP system was significant (r = 0.884, p < 0.001 for maternal and r = 0.765, p < 0.001 for cord blood). Multiple logistic analysis demonstrated that avoidance of simultaneous exposure to hens' eggs and cow's milk (relative risk = 1.3, p < 0.05) as well as soy beans (relative risk = 2.8, p < 0.01) should be advised to mothers with positive allergic histories and/or high total IgE (> 400 IU/ml), especially in women aged more than 35 years who are pregnant with a male child. However, maintenance of healthy lifestyles, especially taking proper exercise and sleeping, and avoidance of inhalant allergens during late pregnancy may be a more important strategy for the reduction of cord blood IgE levels.

Adolescent↗
PubMed1997

Enhanced expression of cytokine-induced neutrophil chemoattractant in rat hepatic allografts during acute rejection.

The kinetics of messenger RNA (mRNA) and protein levels of cytokine-induced neutrophil chemoattractant (CINC) in rat hepatic allografts during acute rejection were investigated. Infiltrating cells were identified by double immunostaining with anti-CINC and anti-macrophage monoclonal antibodies, ED1 and ED2. The serum CINC concentration in untreated hepatic allograft recipients increased significantly at a constant rate over time after transplantation. No significant increases in serum CINC concentrations were observed in hepatic isografts or allografts treated with the immunosuppressant FK506. The number of neutrophils in untreated hepatic allografts increased significantly at a constant rate. Conversely, neutrophil accumulation in isografts or allografts treated with FK506 was much less than in untreated hepaticallografts. Immunostaining revealed that in the portal areas, mononuclear cells infiltrating untreated allograft liver were mainly positive for CINC and that CINC+ cells represented a subpopulation (approximately 25%) of the ED1+ cells. On the other hand, in the sinusoidal areas CINC+ cells were scattered and mainly positive for ED2. Levels of CINC mRNA in liver tissues taken from untreated hepatic allografts increased after transplantation, peaked on day 5, and decreased thereafter. Hepatic allografts treated with FK506 or isografts showed much lower levels of CINC mRNA than untreated allografts. Allogeneic mixed lymphocyte reactions induced CINC production. The cellular source of CINC was mononuclear cells. CINC production in mixed lymphocyte reactions was inhibited in the presence of anti-tumor necrosis factor alpha (TNF-alpha) antibody. These results suggest that enhanced expression of CINC mRNA and prominent accumulation of neutrophils in the liver grafts are characteristic features of the immune response during acute rejection.

Animals↗
PubMed1997

Indication of chemoembolization therapy without gelatin sponge for hepatocellular carcinoma.

This study evaluated the effect of chemoembolization (C-LIP) consisting of ethiodized oil (Lipiodol Ultra Fluid; André Guerbet, Aulnay-sous-Bois, France) and epirubicin, without gelatin sponge on hepatocellular carcinoma (HCC), administered by hepatic arterial infusion. We analyzed the cases from two points of view: the local recurrence rate for hypervascular solitary small HCC (tumor size: < or =3 cm in diameter) and the cumulative survival rate for advanced HCC (stage VI according to the criteria of Liver Cancer Group of Japan) following C-LIP therapy. The C-LIP also was compared with transcather arterial embolization (TAE; C-LIP followed by gelatin sponge) and percutaneous ethanol injection therapy (PEIT). In the small HCC cases, the recurrence rate at 1 year after C-LIP was 77% (10 of 13 patients), while the local recurrence rate was 46% (six of 13 patients) at 6 months and 61% (eight of 13 patients) at 1 year. The local recurrence rate at 1 year was 29% (four of 14 patients) after TAE and 20% (three of 15 patients) after PEIT. These results showed that the effect of local anticancer therapy by C-LIP was not as potent as that of TAE or PEIT. In advanced HCC cases, the cumulative survival rate for 13 patients treated by C-LIP was 72% at 6 months, 36% at 1 year, and 14% at 2 years. However, the survival rates for 13 patients at 6 months, 1 year, and 2 years after TAE were 46%, 23%, and 8%, respectively. There was no difference between the C-LIP patients and TAE patients with regard to the pretreatment liver function. Three patients died within 2 months after the initial TAE. These deaths were mainly due to damage to the noncancerous liver parenchyma. Therapy with C-LIP alone was not appropriate for hypervascular solitary small HCCs, and additional treatment was necessary. We think C-LIP therapy should be selected instead of TAE for advanced HCCs to avoid severe parenchymal damage.

Aged↗