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排序方式: 共有99条查询结果,搜索用时 15 毫秒
1.
The Preclinical Safety Evaluation of Human Monoclonal Antibody against Cytomegalovirus 总被引:1,自引:0,他引:1
MATSUZAWA KEIKO; KOYAMA TAMOTSU; SUGAWARA SHIGEKI; IKEGAWA SUNAO; ASANO SATOSHI; SASAKI SATOSHI; TOMIYAMA TAKAMI; KASAHARA YOSHINORI; OKAMIYA YOSHIAKI; INOUE KYOKO; OHTA TOMOHIRO; MAKITA TOKUTARO 《Toxicological sciences》1992,19(1):26-32
The human monoclonal antibody against cytomegalovinis (Mab C23)was examined pharmacokinetically and toxicologically as partof the preclinical studies prior to approval for human use.Rats given repeated intravenous administrations of Mab C23 producedno antibodies against Mab C23 and maintained a blood Mab C23level in a dose-dependent manner. However, pregnant rabbitsproduced antibodies against Mab C23. The half-life of Mab C23in plasma was 15.9 days in rats, which was similar to that ofnormal human serum -globulin (NHSG). Neither behavioral effectsnor circulatory disturbance was found in mice, rats, and dogseven after a single intravenous injection of 100 or 200 mg/kg,which corresponds to 50 or 100 times the intended clinical dosage.The repeated doses of 2, 10, or 20 mg/kg of Mab C23 on six occasionswith 1- or 2-week intervals elicited a transient decrease inleukocyte counts in rats given 10 or 20 mg/kg, but no adverseeffects in cynomolgus monkeys. Mab C23 did not cause any reproductiveor developmental toxicity when administered to rats and rabbitsat dose levels of 20 mg/kg or less. However, pregnant animalsshowed lower plasma levels of Mab C23 than non-pregnant animals.The chromosomal aberration test disclosed no clastogenicityin human lymphocytes. An immunostaining for Mab C23 revealedno localizations in several tissues of cynomolgus monkeys givenintravenous doses of Mab C23. The preclinical safety evaluationin animals other than rabbits, which produced no antibodiesagainst Mab C23, showed that the behavior of Mab C23 is pharmacokineticallysimilar to that of NHSG and is as safe as NHSG, which has longbeen used as a biological agent. However, because there wasa difference in blood levels of Mab C23 between pregnant andnonpregnant animals, its clinical administration to pregnantpatients should differ from that to non-pregnant patients. 相似文献
2.
YASUKO HATANO SHOICHIRO TANIUCHI MIDORI MASUDA SHOJI TSUJI TAICHI ITO MASAFUMI HASUI YOHNOSUKE KOBAYASHI KAZUNARI KANEKO 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2009,117(2):115-123
Eosinophils are characterized by several functional properties, such as chemotaxis, adhesion, superoxide anion production, and degranulation. In this article, we have studied the role of bacterial ingestion by eosinophils in comparison with that by neutrophils. Eosinophils and neutrophils were purified by using the Percoll gradient method followed by selection with CD16‐coated immunomagnetic beads and centrifugation through a Ficoll‐Hypaque gradient combined with dextran sedimentation, respectively. Both cells were preincubated with anti‐FcγRIIa mAb (CD32 mAb), anti‐FcγRIIIb mAb (CD16 mAb), anti‐CR3 (CD11b mAb), or anti‐CR1 (CD35 mAb) before being examined for phagocytosis of opsonized heat‐killed Staphylococcus aureus (S. aureus). Phagocytosis and production of hydrogen peroxide were simultaneously measured by flow cytometry using S. aureus labeled with propidium iodide and stained with 2′,7′‐dichlorofluorescein diacetate. Eosinophils showed significantly lower activity than neutrophils in both phagocytosis and hydrogen peroxide production. Phagocytosis by both cells was decreased by heat‐inactivated serum. Phagocytosis by neutrophils was significantly inhibited by CD16 mAb and CD32 mAb, whereas that by eosinophils was only inhibited by CD35 mAb. Whereas the mechanism of phagocytosis by neutrophils was mediated by CD16 and CD32, that of eosinophils was modulated by complement receptor 1 (CD35). 相似文献
3.
Antitumor effect of simultaneous transfer of interleukin-12 and interleukin-18 genes and its mechanism in a mouse bladder cancer model 总被引:8,自引:0,他引:8
SATOKO HIKOSAKA ISAO HARA HIDEAKI MIYAKE SHOJI HARA SADAO KAMIDONO 《International journal of urology》2004,11(8):647-652
BACKGROUND: The objectives of this study were to evaluate the antitumor effects of the simultaneous introduction of interleukin 12 (IL-12) and IL-18 genes into a mouse bladder cancer cell line (MBT2). We intended to compare these with those of either gene alone and to investigate the mechanism of the effects induced by the transfer of IL-12 and/or IL-18 genes in this model system. METHODS: We transfected the IL-12 and/or IL-18 genes into MBT2 cells by the liposome-mediated gene transfer method. We confirmed the secretion of IL-12 and/or IL-18 by enzyme-linked immunosorbent assay. Parental (MBT2/P), IL-12-transfected (MBT2/IL-12), IL-18-transfected (MBT2/IL-18) or both IL-12- and IL-18-transfected (MBT2/Both) cells were subcutaneously or intravenously injected into syngeneic C3H mice. To analyze the mechanism of tumor rejection, these clones were subcutaneously injected into naive nude mice and those depleted with natural killer (NK) cells by antibody. RESULTS: MBT2/IL-12, MBT2/IL-18 and MBT2/Both were completely rejected when they were injected subcutaneously or intravenously into syngeneic mice. However, MBT2/IL-12, but not MBT2/IL-18, could grow in nude mice. Moreover, the antitumor effect of MBT2/IL-18 was partially abrogated when injected into nude mice of which NK cells were depleted by antibody treatment. MBT2/Both was completely rejected in both nude mice with and without NK cells. CONCLUSION: The results of the present study indicate that T cells and NK cells seem to play important roles in the antitumor effects by the secretion of IL-12 and IL-18, respectively, and MBT2/Both possesses both mechanisms. 相似文献
4.
SHIGEKI SHOJI M.D. TAKEHIKO SOENO M.D. TOSHIO TAKAHASHI M D. 《The American journal of gastroenterology》1981,75(3):218-221
A rare case of gastrojejunul fistula secondary to gastric cancer is presented. Fluoroscopic examination visualized the passage of contrast medium from the stomach to the small intestine. Gastric fiberscopy revealed cancer on the greater curvature of the corpus perforation into the jejunum. The scope could be inserted readily into jejunum through this perforation. Laparotomy showed that the cancer infiltrated and perforated from the stomach to the jejunum at about 10 cm. from the ligament of Treitz. Distal gastrectomy and resection of 10 cm. of the perforated jejunum were performed. The resected specimen revealed a Borrmann III gastric cancer of the greater curvature perforating the jejunum. 相似文献
5.
Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer 总被引:3,自引:0,他引:3
TOYOAKI UCHIDA HIROSHI OHKUSA HIDEYUKI YAMASHITA SUNAO SHOJI YOSHIHIRO NAGATA TORU HYODO TAKEFUMI SATOH 《International journal of urology》2006,13(3):228-233
BACKGROUND: High-intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease-free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. METHODS: A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and pretreatment prostate-specific antigen (PSA) level were 70 years (range 44-88) and 9.76 ng/mL (range 3.39-89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow-up period for all patients was 18.0 months (range 4-68). RESULTS: The biochemical disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P<0.0001). Multivariate analysis identified pretreatment PSA (P<0.0001) as a independent predictor of relapse. CONCLUSION: High-intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL. 相似文献
6.
7.
TAKASHI MIZUMA SATOSHI MASUBUCHI SHOJI AWAZU 《The Journal of pharmacy and pharmacology》1997,49(11):1067-1071
The absorption, especially the stability and transportability, of the cyclic peptide cyclic glycylphenylalanine (cyclo(Gly-Phe)) and the linear peptides glycylphenylalanine, glycyl-d -phenylalanine and phenylalanylglycine have been studied in rat small intestine. Linear peptides were degraded on the mucosal side and only glycyl-d -phenylalanine appeared on the serosal side. However, cyclo(Gly-Phe) was stable on the mucosal side and appeared on the serosal side. Furthermore, the absorption clearance of cyclo(Gly-Phe) was higher than that of glycyl-d -phenylalanine. In the presence of the peptidase inhibitor bestatin, the degradation of linear peptides was reduced and linear peptides appeared on the serosal side, but only phenylalanylglycine, which is transported by the oligopeptide transporter, was absorbed faster than cyclo(Gly-Phe). The absorption clearance of cyclo(Gly-Phe) was reduced as its concentration was increased from 125 μm to 500 μm . Furthermore, the absorption clearance of cyclo(Gly-Phe) at 125 μm was reduced at 4°C or in the presence of glycylsarcosine and cephalexin, which are transported by the oligopeptide transporter. These results indicated that cyclo(Gly-Phe) was stable enough to be absorbed and was transported in part by the oligopeptide transporter rather than completely by passive diffusion. 相似文献
8.
CHEN SHENG-SONG; YOSHIHARA HARUMASA; SEIYAMA AKITOSHI; HARADA NOBORU; KAWANO SUNAO; TSUJI SHINGO; FUSAMOTO HIDEYUKI; KAMADA TAKENOBU; SHIGA TAKESHI 《Alcohol and alcoholism (Oxford, Oxfordshire)》1995,30(2):187-194
The redox state of cytochrome aa3 was measured at microspots(20µm diameter) within the lobule of perfused rat livers,using reflectance microspectroscopy, and the effect of ethanolinfusion on sublobular distribution of the redox states wasevaluated. A sigmoidal relationship was observed between oxygendelivery and the reduction of cytochrome aa3 in both the periportaland pericentral regions of the liver lobule when the influentO2 concentration was decreased in a graduated manner. This sigmoidalcurve was shifted to the more reduced state by ethanol infusion,with ethanol (25100mM) increasing the degree of cytochromeaa3 reduction in a dose-dependent manner according to the distancefrom the periportal region along a sinusoid. This increase wasspatially heterogeneous within a liver lobule. These data indicatethat ethanol accelerates cytochrome aa3 reduction, with a distinctgradient of reduction along sinusoids but a heterogeneous distributionwithin the liver lobule. 相似文献
9.
10.
GOJOBORI MARIKO; MASHIBA HARUKAZU; MATSUNAGA KEIKO; JIMI SHOJI 《Japanese journal of clinical oncology》1981,11(1):101-108
C3 and C4 concentrations in the serum of uterine cervical cancerpatients and healthy controls were determined and their relationshipto other immunological parameters was studied. Complement levelsin cancer patients were significantly higher than those in thehealthy controls. However, complement levels in cancer patientsin Stage IV were almost the same as those in the controls. Therewas a significant correlation between complement levels andlymphotoxin activity of the lymphocytes. Although lymphocyteresponse to phytohemagglutinin was depressed, elevated complementlevels were maintained in cancer patients in Stages I, II andIII. 相似文献