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Biomedical subjects

K Sasai

Publications and source records attributed to K Sasai.

At least 109 records · Page 6Linked to original sources
PubMed1996

Eimeria tenella: role of carbohydrates on sporozoite at the penetration into cultured cells.

The effects of carbohydrates on the penetration of Eimeria tenella sporozoites into cultured cells were investigated. Eight different carbohydrates that have been known to be on the surfaces of animal cells were added to culture medium during the penetration period. D-Galactose alone inhibited sporozoite penetration into primary chicken kidney cells. When kidney cells were pretreated with D-galactose and infected with E. tenella sporozoites, the penetration was suppressed significantly, but not when the sporozoites were pretreated. In addition, the penetration of sporozoites was suppressed when pretreated with peanut lectin that specifically recognizes D-galactose residues at a concentration of 50 micrograms/ml. The present results suggested that D-galactose residues on E. tenella sporozoite surfaces and the lectin-like receptors that recognize D-galactose of host cells are important factors for penetration.

Animals↗
PubMed1996

Chromosome spreading techniques for primary gastrointestinal tumors.

The requirement for well spread out chromosomes for the cytogenetic analysis of primary gastrointestinal tumors led us to develop new techniques. These techniques involved two main procedures: (1) preliminary incubation with culture medium in the presence of collagenase, Dispase, and colcemid, for 3 h, and (2) treatment with an extremely hypotonic solution (0.044M KCl) for 30 min. The techniques were applied to 11 gastrointestinal malignancies (including 1 early gastric cancer and 1 metastatic liver lesion of colon cancer) and significant increases (P < 0.01) in the number of metaphases of analyzable karyotypes were obtained, compared with a previous method in which the standard hypotonic molarity of KCL (0.075 M) was employed. The mean value for metaphase numbers of the analyzable karyotypes was 37.0 +/- 3.7% in the 5 gastric cancers and 44.7 +/- 4.8% in the 5 colon cancers and 1 metastatic lesion. These values were three times and more than twice, respectively, the values obtained by the previous method. A fluorescence in situ hybridization (FISH) study was carried out on one cologenic tumor, the alpha-satellite centromere-specific probe 17 being used. Deletion of the long arm of chromosome 17 was demonstrated. The method proposed here could yield a sufficient number of metaphases without the use of tissue culture that might cause alteration of karyotype. It can be employed with small biopsy specimens and in studies utilizing the FISH technique.

Aged↗
PubMed1996

Early detection of specific IgE antibody against house dust mite in children at risk of allergic disease.

OBJECTIVES: House dust mite (HDM) is a representative inhalant allergen that triggers allergic disease in childhood. The aim of this study is early detection of HDM-specific IgE antibody and prediction of the risk of a positive reaction to this antibody by in vitro parameters in infants with allergic manifestations. STUDY DESIGN: Levels of HDM IgE in a range below the standard cutoff point of 0.35 U/ml, serum concentrations of IgE, and specific IgE antibodies against egg white, cow milk, and soybeans were determined in 108 infants with allergic manifestations at 6 months of age, and these infants were monitored for conversion of HDM IgE to positive levels greater than 0.35 U/ml up to 5 years of age. The presence of active allergic disease at 5 years of age in relation to HDM-specific IgE was also examined. RESULTS: We were able to determine reliably the HDM IgE values between 0.23 and 0.35 U/ml, using a fluorescent enzyme immunoassay that measured the intensity of fluorescence. The HDM IgE levels increased, resulting in positive values, in 54 of 108 subjects during the first 5 years of life. In multiple regression analysis, an HDM IgE value between 0.23 and 0.35 U/ml, a high serum IgE level, and a positive reaction to specific IgE antibody against egg white in infants at 6 months of age proved to be significant predictors of the future positive reaction to HDM IgE (p = 0.0006, 0.0043, and 0.0001). In particular, the sensitivity and specificity of specific IgE antibody against egg white for the conversion of HDM IgE to positive values were the best among these indicators. Moreover, active allergic diseases were observed significantly more often in children with positive HDM IgE values than in children with negative HDM IgE values at 5 years of age (p < 0.001 for each). CONCLUSIONS: A determination of these predictors in infants at 6 months of age can be used for early detection of HDM IgE and would be valuable in a screening test for later allergic disease among infants with allergic manifestations.

Allergens↗
PubMed1996

Combined effect of clinically relevant doses of emitefur, a new 5-fluorouracil derivative, and radiation in murine tumours.

We investigated the combined effect of radiation and clinically relevant doses of emitefur (BOF-A2), a newly developed anti-cancer agent consisting of a masked form of 5-fluorouracil (5-FU) and a potent inhibitor of 5-FU degradation, in two types of murine tumours. In preliminary pharmacokinetic studies, the area under the curve for 5-FU in plasma, after administration of 12.5 mg kg-1 and 25 mg kg-1 emitefur in mice, appeared to be similar to that obtained on the first day and that on the seventh day, respectively, after starting administration of 400-600 mg day-1 in humans. These doses (12.5 and 25 mg kg-1) of emitefur were evaluated either alone or in combination with single (15 Gy), five-fraction (4 Gy each) or ten-fraction (2.8 Gy each) irradiation using a tumour growth delay assay for SCCVII tumours and in combination with four-fraction (5 Gy each) irradiation using an in vivo-in vitro assay for EMT6 tumours. The anti-tumour and radiation-enhancing effects of 12.5 mg kg-1 emitefur were not significant in any except the ten-fraction experiment. On the other hand, multiple doses of 25 mg kg-1 emitefur given either alone or in combination with radiation produced marked effects. The mean tumour growth delay time (the time to double in volume for treated tumours minus that for untreated tumours) was 8.1 days for five administrations of 25 mg kg-1 emitefur. 10.4 days for five fractions of 4 Gy and 22.1 days for five treatments with the combination of the two. Thus, the increase in growth delay afforded by this combination was at least additive. The effect of four fractions of 5 Gy with 25 mg kg-1 emitefur in EMT6 tumours was lower than that of four fractions of 7.5 Gy, but the effect of five fractions of 4 Gy with this dose of emitefur in SCCVII tumours was similar to the effect of five fractions of 6 Gy, and the effect of ten fractions of 2.8 Gy with 25 mg kg-1 emitefur was much higher than that of ten fractions of 4.2 Gy. In conclusion, emitefur given either alone or in combination with radiation appears to have a significant anti-tumour effect even at clinically relevant dose levels, although a threshold dose exists between 12.5 and 25 mg kg-1. Further clinical studies of this compound are warranted.

Animals↗
PubMed1996

Comparison of in vivo efficacy of hypoxic cytotoxin tirapazamine and hypoxic cell radiosensitizer KU-2285 in combination with single and fractionated irradiation.

Development of strategies to eradicate radioresistant hypoxic cells would be of great benefit for clinical radiotherapy. In the present study, the in vivo effects of a promising hypoxic cytotoxin, tirapazamine (3-amino-1,2,4-benzotriazine 1,4-di-N-oxide), were examined in comparison with those of KU-2285, one of the best hypoxic cell radiosensitizers, in combination with both single and fractionated irradiation. The tumor response was assessed by the standard in vivo-in vitro clonogenic assay using SCCVII tumors in C3H mice and EMT-6/KU tumors in Balb/c mice with different characteristics of tumor hypoxia. With single-dose irradiation (18 Gy), both tirapazamine and KU-2285 showed significant enhancement of cell killing in a dose-dependent manner, but tirapazamine was more effective for SCCVII tumors with acutely hypoxic cells, while KU-2285 was more effective for EMT-6/KU tumors predominantly with chronically hypoxic cells. In fractionated irradiation regimens (4 fractions of 5 Gy at 12 h intervals), tirapazamine showed more marked combined effects at 10 and 20 mg/kg than KU2285 at 100-200 mg/kg in both SCCVII and EMT-6/KU tumors. We concluded that the effectiveness of KU-2285 and tirapazamine was correlated with the nature of tumor hypoxia with single-dose irradiation, whereas tirapazamine appeared more potent than KU-2285 with fractionated irradiation. These findings suggest the potential usefulness of tirapazamine in clinical fractionated radiotherapy.

Animals↗
PubMed1996

Non-Hodgkin's lymphoma of the thyroid. A clinical study of twenty-two cases.

Non-Hodgkin's lymphoma (NHL) of the thyroid gland is a rare disease. In the present study, the survival rate and characteristics were retrospectively analyzed in 22 patients with stage IE and IIE thyroid NHL treated with radiotherapy with or without combination chemotherapy. Seventeen NHL had histological evidence of lymphoma of mucosa-associated lymphoid tissue (MALT) type. The 5-year survival rate was 85% in all patients, with 100% and 63% respectively, for stage IE and stage IIE patients. The highly significant factor correlated with decreased determinate survival was concomitant stridor.

Adult↗
PubMed1996

Characterization of a chicken monoclonal antibody that recognizes the apical complex of Eimeria acervulina sporozoites and partially inhibits sporozoite invasion of CD8+ T lymphocytes in vitro.

A stable chicken hybridoma secreting a monoclonal antibody (mAb) that detects the apical complex of Eimeria acervulina sporozoites has been developed by fusing a thymidine kinase (TK)-deficient chicken myeloma with spleen cells from chickens immunized with sporozoite antigen. The mAb, designated as 6D-12-G10, recognized the apical complex of a sporozoite of 20-21 kDa molecular mass on western blots. Immunoelectron microscopic examination revealed that mAb 6D-12-G10 stained the conoid antigen. Furthermore, mAb 6D-12-G10 inhibited the invasion of sporozoites into CD8+ T cells in vitro. These results suggest that the conoid may play an important role in the recognition and invasion of host cells by Eimeria sporozoites.

Animals↗
PubMed1996

Detection of canine erythrocytes infected with Babesia gibsoni by flow cytometry.

Peripheral blood samples from dogs infected with Babesia gibsoni were analyzed by flow cytometry for parasitized erythrocytes after staining with hydroethidine. Cells identified as positive by flow cytometry were erythrocytes infected with B. gibsoni. Analysis of 26 samples by flow cytometry for % parasitemia revealed a correlation coefficient of 0.97 in comparison to the conventional method of light microscopy.

Animals↗
PubMed1996

Tirapazamine: hypoxic cytotoxicity and interaction with radiation as assessed by the micronucleus assay.

We investigated the cytotoxicity and the interaction with low-dose radiation (1-4Gy) of tirapazamine by the in vitro cytokinesis-block micronucleus (MN) assay. Murine SCCVII and human melanoma (G-361) cells were treated with tirapazamine under aerobic or hypoxic conditions for 1 h and the MN frequency was determined using cytochalasin-B. The cells were also treated with or without tirapazamine or KU-2285 (hypoxic cell sensitiser) under hypoxic conditions and irradiated with or without reaeration of the cell suspensions. A dose-dependent increase of MN frequency was observed by tirapazamine treatment and the hypoxic toxicity ratio was about 130 for SCCVII and 37 for G-361. The radiation dose-response curves of MN frequency suggested that the interaction of tirapazamine with irradiation appeared to be essentially additive in both cell lines. In contrast, the dose-response curve became steeper by KU-2285 treatment. Combined effects of tirapazamine and irradiation on the hypoxic cells were much higher than the radiation effect on aerobic cells at low doses, while the effects of KU-2285 did not exceed that of aerobic irradiation. In conclusion, tirapazamine appeared to be superior to hypoxic radiosensitisers at clinically relevant doses, not because of aerobic radiosensitisation but because of its potent hypoxic cytotoxicity additive to radiation effect.

Animals↗
PubMed1996

The combined antitumour effect of a new 5-fluorouracil derivative, BOF-A2, and radiation in vivo.

We examined the combined effect of radiation and BOF-A2, a newly developed anti-cancer agent consisting of a masked form of 5-fluorouracil (5-FU) and a potent inhibitor of 5-FU degradation in the liver, on murine tumors. Subcutaneous 8-mm-diameter SCCVII tumours grown in the right thigh of C3H/He mice were used. The mice were locally irradiated with single doses of 10-30 Gy or five fractions of 4 Gy for 5 days, alone or in combination with BOF-A2. BOF-A2 at doses of 30, 75 and 150 mg kg-1 was orally administered 2 h before or immediately after single doses of irradiation, while 15 or 30 mg kg-1 of BOF-A2 was given 1 h prior to each fraction of 4 Gy. The effect of BOF-A2 alone was also examined. The antitumour effect was evaluated by a tumour growth delay assay. BOF-A2 alone showed significant tumour growth delay at all doses used in this study. Combination of BOF-A2 and single or fractionated doses of radiation appeared to produce an additive tumour response, which occurred independently of sequence of the two treatments. The combined effect became greater with the dose of radiation and BOF-A2. In conclusion, BOF-A2 and radiation may be efficiently combined.

Animals↗
PubMed1996

Kyoto University experience with intraoperative radiation therapy.

To date, intraoperative radiotherapy has been performed at Kyoto University Hospital in a total of 480 patients with malignancies various sites. Among these, patients with disease of 4 major sites were selected for prognostic analysis. For gastric cancer patients survival was improved by the adjuvant intraoperative radiotherapy compared with gastrectomy alone in those with advanced nodal or serosal involvement [P < 0.05 for n2 + n3' 0.1 > P > 0.05 for s(+)]. Also, the survival for the adjuvant radiotherapy group was significantly improved in patients with stage II-III pancreatic cancer who underwent non-curative resection (P < 0.001). For patients with soft tissue sarcomas of the extremities, intraoperative radiotherapy was performed after the tumours were surgically removed to the greatest e* possible. Operation curability had a great impact on the local tumour control rate (82% for curative resection versus 18% for non-curati resection) and on the long-term survival rates (65% versus 8%, respectively). In patients with osteosarcoma, a large single do* 50-55 Gy was applied to the affected limb in an attempt to achieve local control and limb salvage. By this method, good local control attained, and a 10-year survival rate showed improvement following the introduction of cisplatinum into intensive chemotherapy.

Bone Neoplasms↗
PubMed1996

[Palliative radiation therapy for multiple myeloma].

PURPOSE: Radiation therapy is a useful palliative modality for refractory lesions of multiple myeloma. It has been reported that total doses of 10 to 20 Gy are usually adequate to obtain some degree of pain relief. However, there are many patients who need additional doses to obtain sufficient pain relief. In this study, we retrospectively analyzed the records of patients with multiple myeloma irradiated at our department, in an attempt to develop an effective treatment policy for this disease. MATERIALS AND METHODS: Twenty-nine patients with 53 lesions were treated between 1968 and 1993. Total irradiation doses were 4 to 60 Gy(median 40 Gy) with daily fractions of 2 Gy or less, and 16 to 51 Gy(median 30 Gy) with daily fractions greater than 2 Gy. Evaluated were 59 symptoms, including pain (68%), neurological abnormalities (15%), and masses (28%). RESULTS: Symptomatic remission was obtained in 33 of 36 (92%) lesions with pain, 6 of 8(75%) with neurological abnormalities, and 13 of 15(87%) mass lesions. Pain was partially relieved at a median TDF of 34, and completely at a median TDF of 66(equivalent to 40-42 Gy with daily fractions of 2 Gy). CONCLUSIONS: Radiation therapy is an effective and palliative treatment method for symptomatic multiple myeloma. However, the treatment seems to require higher radiation doses than those reported to obtain adequate relief of symptoms.

Adolescent↗
PubMed1995

Optical isomers of a new 2-nitroimidazole nucleoside analog (PR-350 series): radiosensitization efficiency and toxicity.

PURPOSE: A new 2-nitroimidazole nucleoside radiosensitizer, PR-350 (1-[1',3',4'-trihydroxy-2'-butoxy]-methyl-2-nitroimidazole), has been reported to be as efficient as and less toxic than etanidazole. This compound is racemic, and it was recently optically resolved into two isomers, PR-68 (2'R,3'S type) and PR-69 (2'S,3'R type). The other two isomers, PR-28 (2'S,3'S type) and PR-44 (2'R,3'R type), were asymmetrically synthesized. In the present study, we investigated the properties, sensitizing activity, and toxicity of PR-350 and the four optical isomers in comparison with those of other 2-nitroimidazole hypoxic cell radiosensitizers, etanidazole, KU-2285, KIN-804, and RP-170. Because PR-350 and PR-28 can be industrially synthesized, we evaluated whether either of these two drugs are suitable for further investigation. METHODS AND MATERIALS: In an in vitro study, EMT-6 cells were irradiated at a dose of 1-3 Gy under hypoxic conditions in the presence of the drugs at a concentration of 1 mM. A combined cytokinesis-block micronucleus and chromosomal aberration assay was performed. To assess the in vivo effects, colony assay and growth delay assay were performing using SCCVII tumor-bearing C3H mice. The mice received 16-24 GY 10-40 min after administration of 50-200 mg/kg of the drugs. Toxicity and pharmacokinetics in mice were also investigated. RESULTS: The sensitizer enhancement ratio (SER) in the in vitro cytokinesis-block micronucleus assay increased in the following order: PR-69 (1.27) approximately equal to PR-28 (1.31) approximately equal to PR-44 (1.38) approximately equal to PR-350 (1.41) approximately equal to PR-68 (1.47) < etanidazole (1.79) < KIN-804 (2.03) approximately equal to KU-2285 (2.30). The SER at a dose of 200 mg/kg and at an interval of 20 min (optimal interval) in the in vivo-in vitro colony assay increased as follows: PR-44 (1.26) approximately equal to PR-28 (1.29) < PR-69 (1.34) approximately equal to etanidazole (1.35) approximately equal to PR-350 (1.36) < RP-170 (1.41) approximately equal to PR-68 (1.41) < KU-2285 (1.49). The growth delay assay also showed that PR-350 was less efficient than KU-2285 and more efficient than PR-28. PR-350 and the four isomers had similar reduction potentials, but PR-28 and PR-44 were more hydrophilic than PR-68 and PR-69. The LD50 in mice were 5.8 g/kg for PR-350, approximately 7 g/kg for PR-28, 4 g/kg for PR-68, and 6 g/kg for PR-44 and PR-69. The concentration of PR-28 in the murine sciatic nerve was lower than that of PR-350. CONCLUSION: In vivo radiosensitizing activity differed among the four optical isomers, which appeared to be due, at least in part, to differences in lipophilicity. Although PR-28 was the least toxic, its low sensitization efficiency does not warrant clinical trials. Among the PR compounds, PR-68 appears to be most efficient, but optical resolution of PR-68 from PR-350 is expensive, and asymmetrical synthesis of PR-68 is not established. Therefore, PR-350 seems to be most suitable for further investigation among the PR-350 series compounds, considering its higher efficiency compared with PR-28 and PR-44, and established synthesis.

Animals↗
PubMed1995

Use of acetylcholine (Ach) for spreading metaphase chromosomes and application to the cytogenetic analysis of human stomach cancers.

Cytogenetic studies of biopsy specimens endoscopically obtained from gastric cancers were performed in our laboratory. The necessity for well-spread chromosomes for analysis has resulted in the development of a new technique, in which culture medium containing acetylcholine (Ach) is used; with this new technique, the number of metaphases of analyzable karyotypes was significantly increased (P < 0.01 compared with a previous method in which Ach was not used). The mean ratio of metaphase numbers of analyzable karyotypes in four cases in which Ach was used was 38.1 +/- 8.1%, a value more than four times the number in the seven cases in which Ach was not used. It is possible that Ach may decrease the viscosity of the cytoplasm in gastric cancer cells by disrupting microfilaments.

Acetylcholine↗
PubMed1995

Assessment of micronucleus induction in SCCVII cells treated with bioreductive agents, WIN 59075 (SR 4233) and mitomycin C, under aerobic and hypoxic conditions.

WIN 59075 (SR4233, tirapazamine) is a promising bioreductive antitumor agent preferentially more toxic to hypoxic cells and presently undergoing phase I clinical trials. In this investigation, we have examined the applicability of the cytokinesis-block micronucleus assay to assess the effects of bioreductive agents. SCCVII tumor cells were treated with WIN 59075 or mitomycin C at various concentrations under aerobic and hypoxic conditions. Significant induction of micronuclei in binucleate cells was demonstrated in a dose-dependent fashion and it appeared to be strongly correlated with the loss of clonogenicity in the colony assay. Both agents showed selectively higher toxicity to hypoxic cells than to aerobic cells and the ratios of the concentrations required to obtain the equivalent effects under aerobic and hypoxic conditions could be also estimated by this method as follows: the hypoxic toxicity ratios were 120-130 for WIN 59075 and 3.0-3.3 for mitomycin C. For several favorable characteristics, the cytokinesis-block micronucleus assay can provide an alternative, rapid, and reproducible means for evaluation of antitumor activities from chromosomal breakage caused by the bioreductive agents.

Dose-Response Relationship, Drug↗
PubMed1995

Increased levels of serum IgE in children of mothers with systemic lupus erythematosus.

Various allergic diseases have been described in patients with systemic lupus erythematosus (SLE). In the present study, we evaluated the prevalence of allergic disease and serum IgE levels in 36 children of 26 mothers with SLE. None of the subjects had any rheumatic symptoms. There was at least one type of allergic disease in 28 (78%) of the 36 children of mothers with SLE, as compared with 30% in Japanese control children (P < 0.01). The prevalence of atopic dermatitis and bronchial asthma was higher in children of mothers with SLE (64% and 28%) than in controls (19% and 9%) (P < 0.01, respectively). Fourteen of the 36 subjects (39%) had higher levels of serum IgE than those of normal range for age-matched healthy Japanese children with no atopic family disease in the immediate family history, and these children had atopic disease. Among the 14 children with high serum-IgE levels, seven had neither immediate nor remote family history of atopic disease, while the others had an immediate family history of atopic disease. We think that genetic factors may influence the presence of allergic disease in children of mothers with SLE, and that the increased serum IgE levels in children of SLE mothers with no allergic family history may be a part of subclinical immunologic abnormalities related to SLE.

Case-Control Studies↗
PubMed1995

Eimeria tenella infection induces recrudescence of previous Salmonella enteritidis infection in chickens.

Four experiments were conducted to examine the effect of Eimeria tenella infection on the recrudescence of Salmonella enteritidis in previously infected chickens. Significant recrudescence of cecal colonization in the birds challenged with E. tenella was observed at 3 wk after S. enteritidis infection in Experiment 1, at 3 and 4 wk in Experiment 2, and at 3, 4, and 5 wk in Experiments 3 and 4. The recrudescence was indicated by .81 to 6.31 logs increase in cecal S. enteritidis counts and by higher percentages of ceca that were culture-positive. The possible prolonged cecal S. enteritidis shedding from chickens infected with coccidia into the environment might be important for the perpetuation of S. enteritidis infectious cycle. Except for Experiment 1, in which a significant higher culture-positive rate of the liver was detected in the coccidia-infected group, no significant difference of culture-positive rate of liver and spleen between the treatments was observed. The recrudescence of previous S. enteritidis infection caused by E. tenella infection was obviously related to the initial S. enteritidis dose size and time of exposure to coccidia.

Animals↗