Biomedical subjects

K Sasai

Publications and source records attributed to K Sasai.

At least 163 records · Page 9Linked to original sources

PubMed1990

Expression of Fc epsilon R2/CD23 on peripheral blood macrophages/monocytes in Kawasaki disease.

We analyzed the expression of Fc epsilon R2/CD23 on peripheral blood macrophages/monocytes in 12 patients with Kawasaki disease (KD) using a fluorescence-activated cell sorter. The absolute counts of CD14+ macrophages/monocytes and CD23+ macrophages/monocytes were high, and were positively correlated during the acute stage of KD. These results indicate that the increased number of macrophages/monocytes during acute KD have the Fc epsilon R2/CD23 antigen present on the surface of the cells, suggesting that peripheral blood macrophages/monocytes have been activated.

Acute Disease↗

PubMed1990

Effect of recombinant human granulocyte colony-stimulating factor on granulocytopenia in mice induced by irradiation.

We report the effect of human granulocyte colony-stimulating factor (hG-CSF) on the recovery from granulocytopenia induced by irradiation. Female 9-week old C3H/He mice were used. The irradiation schedule was as follows: Group 1 and 2 received whole-body irradiation of 1 Gy and 5 Gy, respectively, on day 0; Group 3 and 4 received whole-body irradiation of 0.5 and 1.0 Gy, respectively, for 5 consecutive days; Group 5 received upper hemibody irradiation of 3 Gy for 5 consecutive days. Daily subcutaneous injections of G-CSF (3 x 10(5) Unit/mouse) or 0.3 ml of saline to each group were started from the day after the first irradiation and continued for 18 days. Mice were sampled randomly from each group, and the total number of leukocytes, erythrocytes of peripheral blood, nucleated cells in femur, and spleen weight were counted and measured, respectively, on day 0, 3, 5, 7, 9, 12, and 18. The leukocyte counts decreased with an increase in radiation doses. In Group 1 and 2 mice, G-CSF enhanced the leukocyte count more than saline. In Group 3 mice, the recovery of leukocytopenia was facilitated by G-CSF, but in Group 4 mice, G-CSF had no effect on the leukocyte count decrease or on leukocytopenia recovery. In Group 5 mice, G-CSF greatly affected leukocytopenia recovery. Increase in spleen weight paralleled the peripheral leukocyte count. Daily administration of recombinant hG-CSF accelerated the granulocytopenia recovery which was induced by irradiation, and it may be a useful therapeutic agent for treating myelosuppressive cases.

Agranulocytosis↗

PubMed1990

High dose, external beam and intraoperative radiotherapy in the treatment of resectable and unresectable pancreatic cancer.

Ninety patients with pancreatic cancer were treated by external beam radiotherapy (EBRT) and/or intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of a historical control comprising 112 patients treated by surgery alone. At an early stage of this study, postoperative EBRT (50-60 Gy) or IORT (25-33 Gy) was given alone, but recently the two modalities have been combined. The combination of high doses of EBRT and IORT was well tolerated provided that the gastrointestinal tract was not irradiated during IORT. Although EBRT plus IORT appeared to yield better results than either EBRT or IORT alone, the difference was not significant on multivariate analysis, and patients receiving EBRT, IORT, or EBRT + IORT were grouped together. Patients receiving radiotherapy in addition to macroscopically curative surgery had a slightly longer median survival time (14 months) than those receiving curative surgery alone (10 months), but the 3-year survival rate was similar (21% vs. 19%). In patients who underwent noncurative resection, the median survival time was significantly longer for the irradiated group (12 months) than for the control group (6.5 months). Also, in patients with unresectable lesions but no distant metastases, irradiation prolonged the median survival time significantly (8 vs. 3.5 months). In this group, there was one 5-year survivor, who received EBRT of 55 Gy plus IORT of 30 Gy to his unresectable pancreatic body lesion. Patients with metastases were also treated for palliation of symptoms, but it was found that irradiation prolonged the median survival time even in such cases (4.5 vs. 2.5 months). Based on these results, we plan to use EBRT plus IORT in all pancreatic cancer patients with no metastases.

Adult↗

PubMed1990

Pharmacokinetics of 2-nitroimidazole hypoxic cell radiosensitizers in rodent peripheral nervous tissue.

The concentrations of seven 2-nitroimidazoles--including misonidazole, etanidazole (SR-2508), pimonidazole (Ro 03-8799), desmethylmisonidazole (Ro 05-9963), RK28, RP170, and KU2285--were measured in the sciatic nerves of C3H/He mice using reverse-phase high-performance liquid chromatography. Drug exposure to the peripheral nervous system was highest for misonidazole, followed by desmethylmisonidazole, etanidazole, pimonidazole and RK28. The lower drug exposure of pimonidazole and RK28 seemed to be related to their lower hydrophilicity. The apparent biological half-lives of the compounds in the peripheral nerves were correlated to their hydrophilicity: the more hydrophilic the compound, the longer the apparent biological half-life in the peripheral nervous tissue of the mice. Measurement of drug exposure in the rodent peripheral nervous system, rather than in the brain, was a better indicator for estimating the occurrence of clinical peripheral neuropathy by 2-nitroimidazoles.

Animals↗

PubMed1990

Immunohistochemical evidence of the extracellular localization of calcium-activated neutral protease (CANP) in rabbit skeletal muscle, lung and aorta.

The subcellular localization of calcium-activated neutral protease requiring a millimolar calcium concentration (m-CANP) was examined by light and electron microscopy in various tissues of the rabbit, using an immunoperoxidase method with a monoclonal antibody (1C6D1). In skeletal muscles, specific staining for m-CANP was recognized on collagen fibrils (ca 40 nm in diameter) with a periodic banding pattern. In the lung, dense reaction products were precipitated on elastic fibers under the bronchial epithelia. In the aorta, tunica intima and adventitia were intensely stained. Dense reaction products were observed on collagen fibrils and elastic fibers. Basal laminae, on the other hand, were not stained by anti m-CANP antibody in these tissues. These findings suggest that m-CANP may be involved in the regulation of the structure and function of the extracellular matrix.

Animals↗

PubMed1990

Combined effect of radiation and YM-881 (SMANCS) on murine tumors and bone marrow.

The combined effect of radiation and YM-881 (SMANCS) was studied in vitro and in vivo. When 0.25 microgram/ml of YM-881 was simultaneously combined with radiation, during and after irradiation for 30 min in total, Dq decreased from 3.3 Gy to 1.4 Gy without changing D0 in the dose-survival curve of exponentially growing SCC VII tumor cells. Five or ten times administrations of 0.1 mg/kg YM-881 at an interval of 24 h did not inhibit tumor growth. However, administration of 0.1 mg/kg YM-881 just before every irradiation which was repeated five times at an interval of 24 h yielded dose modifying factors (DMFs) of 1.8-1.2 when the tumor response to treatment was evaluated by the time for the tumors to regrow to three times the original volume. Administration of YM-881 ten times just before every irradiation yielded DMFs of 1.3-1.2. Adverse effects of the combination on bone marrow were examined by spleen colony assay. After five injections of 0.1 mg/kg YM-881, the mean number of CFU-S per femur decreased to 77% of the pretreatment level, but this was not significant statistically (0.1 greater than p greater than 0.05). The slope of radiation response curve for CFU-S per femur was not affected by the combination.

Animals↗

PubMed1990

[Hypoxic cell radiosensitizer present status and problems from viewpoint of clinical radiotherapy].

The results of clinical trials of hypoxic cell radiosensitizers were reviewed in order to clarify the present status and problems in this field. Most trials failed to show an effectiveness of the combination, however, some ENT tumors and bladder cancers were improved in local tumor responses and survivals. A selection of the patients suitable for the combination and development of simple method for the selection are indispensable. SERs necessary for clinical radiotherapy are considered to be larger than 1.2 at 2 Gy fraction level. Present hypoxic cell radiosensitizers have no significant effects on alpha values. Since radiation responses at low radiation dose ranges are dominated by alpha values, the chemicals having an effects on alpha values have to be developed.

Cell Hypoxia↗

PubMed1990

Plasma immunoreactive leukotriene C4 levels in patients with Kawasaki disease.

The incidence of wheezing in Kawasaki disease (KD) has been investigated retrospectively. We measured plasma immunoreactive-leukotriene C4 (i-LTC4) levels of patients with KD. Wheezing was observed in 32 (12.5%) of the 256 patients with KD. Patients who had a prior history of bronchial asthma wheezed more frequently than other patients. During the acute stage of KD, plasma i-LTC4 levels both of wheezing and nonwheezing were significantly higher than those of healthy children. During the convalescent stage, plasma i-LTC4 levels of wheezing cases were higher than those of nonwheezing cases. We speculate that LTC4 contributes to the appearance of inflammatory symptoms during the acute stage of KD. During the convalescent stage when patients were taking aspirin, the presence of wheezing was associated with increased plasma levels of i-LTC4. More attention should be paid to the appearance of wheezing during the course of KD, especially in those cases in which the patient has a prior history of bronchial asthma.

Acute Disease↗

PubMed1990

Treatment of murine SCC VII tumors with localized hyperthermia and temperature-sensitive liposomes containing cisplatin.

The release of cisplatin (CDDP) encapsulated in temperature-sensitive unilamellar liposomes to murine SCC VII carcinoma by localized hyperthermia and the effects of the treatment on tumor growth were studied. A transition temperature of the temperature-sensitive liposomes containing cisplatin (LIP-CDDP) was 41 degrees C. Twenty-four hours after injection of LIP-CDDP, the heated tumors (42 degrees C, 60 min) contained 3.3 times more CDDP than the unheated tumors receiving free CDDP. Although the uptake of liposome-associated CDDP by liver was approximately threefold greater at 1.5 h after injection than uptake of free CDDP, it decreased about 50% over a 24-h period. No difference in uptake of the two forms of CDDP by kidney was observed. The combination of LIP-CDDP and localized heating at 42 or 43 degrees C was more effective relative to the amount of CDDP in delaying tumor growth than that of free CDDP and hyperthermia. Treatment with LIP-CDDP plus local heating resulted in a dose-modifying factor of 5.3 when compared with free CDDP and no hyperthermia. The dose-modifying factor was 2.8 when treatment with LIP-CDDP and heat was compared with treatment with free CDDP and heat. Thus CDDP could be released selectively from the temperature-sensitive liposomes by heat and resulted in both a greater uptake of the drug and a delay in tumor growth.

Animals↗

PubMed1989

Variation in tumor response to fluosol-DA (20%).

The effects of Fluosol-DA 20% (FDA) and carbogen (95% O2/5% CO2) on radiosensitivity of the three experimental tumors, SCC VII tumor, RIF-I tumor, and transplanted mammary tumor of C3H/He mouse, subcutaneously inoculated in the leg were examined. The effect of FDA plus carbogen, and carbogen alone on radiosensitivity of SCC VII and RIF-I tumors was tested using the in vivo-in vitro assay. The growth curves were obtained for both SCC VII tumor and transplanted mammary tumor. The effect of the combination of FDA and carbogen was only observed in the transplanted mammary tumor. In the other two tumors, only the effect of inspiring carbogen was observed. We concluded that the effect of FDA on the radiosensitivity of experimental tumors varies with the kind of tumor systems.

Animals↗

PubMed1989

Importance of tumor affinity of nitroazoles in hypoxic radiosensitization.

In vitro and in vivo sensitizing activities of a variety of nitroazole derivatives including misonidazole (MISO), SR-2508, and RSU-1069 were correlated by the aid of pharmacokinetic measurements of the drug uptake in animal solid tumors. The sensitizer enhancement ratio in vivo (SERvivo) on solid tumors increased linearly with the square root of administrated dose (Ds). The specific activity (A) in vivo of nitroazoles was evaluated from the square-root empirical relationship, SERvivo = 1.00 + A D1/2S. The intratumor concentration of nitroazoles at a given time t after administration was in proportion to the DS, in which the proportional constant was defined as the tumor-affinity factor FT,t. The absolute molar activity alpha M defined by A(M/FT,t)1/2, where M is the molecular weight of nitroazoles, showed a linear relationship with the SER in vitro (SERvitro) at 1 mM of sensitizers. The sensitizer dose required to achieve an SERvivo of 1.5 (DS,1.5) decreased and thus the overall sensitizing efficiency on animal solid tumors increased as the FT,t became greater.

Animals↗

PubMed1989

Characteristics of fluorinated nitroazoles as hypoxic cell radiosensitizers.

Types of 2-nitroimidazoles and 3-nitro-1,2,4-triazoles bearing one or two fluorine atoms on their side chains were synthesized to evaluate their physicochemical properties, radiosensitizing effects, and toxicity. The reduction potential of the compounds containing one fluorine was similar to that of misonidazole (MISO), whereas that of the difluorinated compounds was slightly higher. Both mono- and difluorinated compounds had an in vitro sensitizing activity comparable to or slightly higher than that of MISO. The fluorinated 3-nitrotriazoles were almost as efficient as the 2-nitroimidazoles with the same substituent. In vivo, some of the compounds were up to twice more efficient than MISO, whereas others were as efficient as MISO. Toxicity in terms of LD50/7 in mice was quite variable depending on the side-chain structure; the amide derivatives were less toxic than MISO, whereas the alcohol and ether derivatives were more toxic. In view of the radiosensitizing effect and toxicity in vivo, at least one compound, KU-2285 (a 2-nitroimidazole with an N1-substituent of: CH2CF2CONHCH2CH2OH) has been found to be as useful a hypoxic cell sensitizer as SR-2508.

Animals↗

PubMed1989

The effect of arterial oxygen content on the results of radiation therapy for epidermoid bronchogenic carcinoma.

Anemia is believed to be an important prognostic factor in treating cancer patients by radiation therapy. One possible explanation for this is tumor oxygenation. With respect to tumor oxygenation, the arterial oxygen content (CaO2) may be of more importance than the hemoglobin (Hb) level. This study shows the relationship between the CaO2 and tumor response to radiation therapy. Forty-two patients with epidermoid bronchogenic carcinoma, treated by irradiation alone between April 1982 and March 1986, were reviewed. Regression of the tumor after radiation therapy was calculated as a percent change in the tumor area. Arterial oxygen partial pressure (PaO2), Hb level, and percent oxygen saturation of Hb in arterial blood (SaO2) were measured within 2 weeks of commencement of radiation therapy and the CaO2 was calculated. The rank correlation coefficients between the maximum percent regression of the tumor and the PaO2, the Hb level and the CaO2 were 0.36, 0.34, and 0.46, respectively. Statistical analyses of the data indicate that the group of patients with CaO2 over 14.5 ml/dl exhibited greater tumor regression and longer survival periods than the group of patients with CaO2 below 14.5 ml/dl. Similarly patients with PaO2 over 90 mmHg or Hb level over 11 g/dl, exhibited significantly greater tumor regression and longer survival periods than those with PaO2 below 90 mmHg and Hb level below 11 g/dl. There were no significant differences in the length of survival periods with respect solely to the Hb level or the PaO2. It was concluded that the CaO2 is more important than the Hb level in determining tumor response to radiation therapy. This is considered as important indirect evidence of the existence of hypoxic fractions of cells in human tumors.

Adult↗

PubMed1989

A new, potent 2-nitroimidazole nucleoside hypoxic cell radiosensitizer, RP170.

The radiosensitizing activity, acute toxicity and pharmacokinetics of RP170, a new hypoxic cell radiosensitizer, were compared with those of misonidazole (MISO) and SR2508. RP170 belongs to the group of 2-nitroimidazole nucleosides, which are designed to be selectively excluded from the neural tissue. The reduction potential of RP170 was similar to that of MISO and SR2508. The partition coefficients in octanol/water of RP170, MISO, and SR2508 were 0.094, 0.35, and 0.021, respectively. The radiosensitizing activity of RP170 was similar to that of MISO and SR2508 in vitro and in vivo. There was no significant difference in the radiosensitizing activity of RP170 in vivo between intravenous and intraperitoneal administration. The acute toxicity of RP170 was the same as that of SR2508. Pharmacokinetic evaluation showed that the concentration of RP170 in the brain was as low as that of SR2508. RP170 is expected to have the same radiosensitizing effects as MISO and SR2508, and to be less neurotoxic than MISO.

Animals↗

PubMed1989

Radiosensitizing hypoxic cells with new 3-nitro-1,2,4-triazole derivatives in vitro and in vivo.

The new regioisomer derivatives 4a-f and 5a-f of 3-nitro-1,2,4-triazole (3-NTR) were synthesized for the development of new radiosensitizers of hypoxic cancer cells for radiotherapy. N(2)-Substituted 3-NTR derivatives 5a-f were stronger radiosensitizers of hypoxic cells in vitro (Chinese hamster V79 cells) than N(1)-substituted 3-NTR derivatives 4a-f, but in vivo they were weaker (SCCVII carcinoma cells inoculated into C3H/He mouse).

Animals↗

PubMed1989

[A primary adenocarcinoma of the appendix, accompanied with 5 ileocolonic fistulae].

A primary adenocarcinoma of the appendix is a rare lesion, and this paper reports a case of a primary adenocarcinoma of the appendix, but with the inclusion of 5 fistulae. According to the classification by Uihlein & McDonald, this histology is of the colonic type. The first known case accompanied with a fistula was reported by Haldane (1862) in the English-language literature and by Shiraishi et al. (1954) in Japan. Since then, 21 cases have been found in the Japanese literature. The patient underwent an operation and his prognosis has been considered good. A review of some the relevant literature is discussed with regard to the pathology, diagnosis, and treatment.

Adenocarcinoma, Mucinous↗

PubMed1989

[Influence of hemoglobin level, arterial oxygen partial pressure and arterial oxygen content on the results of radiation therapy in lung squamous cell cancer].

It is believed that anemia is an important prognostic factor in the case of cancer patients treated by radiation therapy. One possible explanation for this is tumor oxygenation. With respect to tumor oxygenation, the arterial oxygen content (CaO2) may be more direct indicator than hemoglobin (Hb) level. Fourty-two patients with squamous cell lung cancer treated solely by irradiation were reviewed. It was found that CaO2 was more important than the Hb level in determining a tumor response to radiation therapy. This is considered as important indirect evidence of the existence of hypoxic fractions of cells in human tumors.

Adult↗

PubMed1989

The correlation between cell survival curve and dose response curve of micronucleus (MN) frequency.

The correlation between cell survival curve and dose response curve of MN frequency following irradiations was studied using cytokinesis-block method. Both dose response curves were analyzed by linear quadratic model, i.e. SF = exp (-alpha D-beta D2) and MN frequency = aD + bD2 + C. A good correlation between alpha/beta and a/b ratios was observed in repeated paired experiments (= 0.97). When the cells were treated with BUdR, alpha-type radiosensitizer, a value in dose response curve of MN frequency increased but b value did not. These data present that MN frequency assay using cytokinesis-block method is available as a tool of rapid assay of radiosensitivity of cells.

Animals↗