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Biomedical subjects

Y Kano

Publications and source records attributed to Y Kano.

At least 55 records · Page 3Linked to original sources
PubMed2000

Pharmacological properties of traditional medicines. XXVI. Effects of Sansohnin-to on pentobarbital sleep in stressed mice.

We investigated the effect of Sansohnin-to (SAT) on changes of duration in sodium pentobarbital (PB)-induced sleeping time caused by five types of stress. SAT reversed shortened PB sleep in repeated cold stress or 45 min-restraint stress tests and the prolonged PB sleep in 120 min-restraint stress. SAT did not reverse the shortened PB sleep in the specific stress state caused by an alternating rhythm in temperature stress or social isolation stress. In addition, SAT influenced both shortened PB sleep in 45 min-restraint stress and prolonged PB sleep in 120 min-restraint stress. SAT had no effect on PB sleep in unstressed control mice. These findings suggest that SAT has unusual activity, different from synthetic narcoleptics such as benzodiazepine. This is because SAT had no effect on PB sleep in unstressed mice, and it reverses stress-induced decrease and/or increase in PB sleep by improving stress-induced functional changes in the central nervous system, rather than by acting like a synthetic hypnotic on the gamma-aminobutyric acidA (GABA(A)) receptor.

Administration, Oral↗
PubMed2000

Schedule-dependent interaction between raltitrexed and 5-fluorouracil in human colon cancer cell lines in vitro.

Raltitrexed (Tomudex) is a novel thymidylate synthase inhibitor with significant activity against advanced colorectal cancer. We studied the cytotoxic interactions of raltitrexed and 5-fluorouracil (5-FU) in four human colon cancer cell lines on various schedules. The cell growth inhibition after 5 days was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytotoxic interactions at the IC80 level were evaluated by the isobologram method. Simultaneous exposure to raltitrexed and 5-FU for 5 days produced additive to synergistic effects in Colo201 cells, and produced additive effects in Colo321, LoVo, and WiDr cells. Simultaneous exposure to raltitrexed and 5-FU for 24 h produced additive effects in Colo201, LoVo, and WiDr cells, and produced antagonistic effects in Colo320 cells. Sequential exposure to raltitrexed for 24 h followed by 5-FU for 24 h produced additive effects in Colo201, Colo320, and LoVo cells, and produced antagonistic effects in WiDr cells. The reverse sequence produced additive effects in Colo201 cells, and produced antagonistic effects in Colo320, LoVo, and WiDr cells. Simultaneous exposure to raltitrexed and 5-FU for 4 h and sequential exposure to raltitrexed for 4 h followed by 5-FU for 4 h with a 20-h interval produced additive effects, while the reverse sequence produced antagonistic effects in LoVo and WiDr cells. These findings suggest that the simultaneous administration of raltitrexed and 5-FU or the sequential administration of raltitrexed followed by 5-FU may be the optimal sequence, while the reverse sequence may be inappropriate. Preclinical and clinical studies of the simultaneous administration of raltitrexed and 5-FU and the sequential administration of raltitrexed followed by 5-FU are required to better understand the antitumor, toxic, and pharmacokinetic interactions of this combination in order to develop the combination chemotherapy of raltitrexed and 5-FU.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Effect of age on rat aortic responses to acetylcholine and nitric oxide donor (NOC-18).

The purpose of the present study was to examine the effects of age on vascular responses to acetylcholine (ACh) and NO-releasing compound (NOC-18). The studies were performed in young (4 months old, n = 8) and old (22 months old, n = 6) male rats. Responses to ACh and NOC-18 were examined in vitro by using isolated abdominal aortic rings. The maximum relaxation response to ACh, an endothelium-dependent vasodilation, was lower in aortas from old rats. Sensitivity (mean effective concentration; EC50) of ACh in old rats was significantly less than in young rats. There were no differences in maximum NOC-18-induced relaxation, an endothelium-independent vasodilation, in aortas from young and old rats. On the other hand, the concentration-response curve for NOC-18 was shifted to the right and the sensitivity (EC50 to NOC-18) was lower in old rats. These results indicated that both endothelium-dependent vasodilation induced by ACh and endothelium-independent vasodilation induced by NOC-18 are impaired in aorta from old rats.

Acetylcholine↗
PubMed1999

Determination of imidapril and imidaprilat in human plasma by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

A sensitive and specific assay of imidapril and its active metabolite, imidaprilat, in human plasma has been developed. This method is based on rapid isolation and high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-tandem mass spectrometry (MS-MS). Imidapril and imidaprilat were isolated from human plasma using OASIS HLB (solid-phase extraction cartridge), after deproteinization. The eluent from the cartridge was evaporated to dryness, and the residue was reconstituted in mobile phase and injected into the HPLC-ESI-MS-MS system. Each compound was separated on a semi-micro ODS column in acetonitrile-0.05% (v/v) formic acid (1:3, v/v). The selected ion monitoring using precursor-->product ion combinations of m/z 406-->234 and 378-->206, was used for determination of imidapril and imidaprilat, respectively. The linearity was confirmed in the concentration range of 0.2 to 50 ng/ml in human plasma, and the precision of this assay, expressed as a relative standard deviation, was less than 13.2% over the entire concentration range with adequate assay accuracy. The HPLC-ESI-MS-MS method correlates well with the radioimmunoassay method, therefore, it is useful for the determination of imidapril and imidaprilat with sufficient sensitivity and specificity in clinical studies.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

A phase II study of irinotecan and infusional cisplatin with recombinant human granulocyte colony-stimulating factor support for advanced non-small-cell lung cancer.

PURPOSE: We administered chemotherapy consisting of a combination of 5-day continuous infusion of cisplatin (20 mg/m2 per day) plus irinotecan (160 mg/m2 per day, as a bolus, on day 1) with recombinant human granulocyte colony-stimulating factor (rG-CSF) support to previously untreated advanced non-small-cell lung cancer (NSCLC) patients, and evaluated the effectiveness and safety of this therapy. PATIENTS: Enrolled in the study were 41 NSCLC patients. RESULTS: Of the 41 patients, 24 achieved a partial response. The response rate was 58.5% (95% confidence interval, 42.2% to 74.8%), with a median response duration of 32.1 weeks. The median survival time was 44.8 weeks and the 1-year survival rate was 44%. A total of 100 courses of therapy were given. The major toxic effects were grade 3 or 4 diarrhea (23%), granulocytopenia (20%), thrombocytopenia (15%) and anemia (15%). There were no treatment-related deaths. CONCLUSIONS: Combination chemotherapy with irinotecan plus infusional cisplatin with rG-CSF support was well tolerated and effective in patients with advanced NSCLC.

Adult↗
PubMed1999

Schedule-dependent interactions between paclitaxel and etoposide in human carcinoma cell lines in vitro.

Clinical studies of paclitaxel in combination with etoposide against solid tumors have been carried out. The combination schedules used in these studies are different. We studied the cytotoxic effects of paclitaxel with etoposide against four human cancer cell lines in vitro to determine the optimal schedule of this combination at the cellular level. Cells were exposed simultaneously to paclitaxel and to etoposide for 24 h or sequentially to one drug for 24 h followed by the other for 24 h, after which they were incubated in drug-free medium for 4 and 3 days, respectively. Cell growth inhibition was determined by an MTT reduction assay. The effects of drug combinations at concentrations producing 80% inhibition (IC(80)) were analyzed by the isobologram method of Steel and Peckham. The cytotoxic effect of paclitaxel and etoposide was cell line- and schedule-dependent. Simultaneous exposure to paclitaxel and etoposide for 24 h produced additive effects in the lung cancer cell line A549 and ovarian cancer PA1 cells, and antagonistic effects in the breast cancer cell line MCF7 and colon cancer WIDr cells. Sequential exposures to paclitaxel followed by etoposide and vice versa produced additive effects in all four cell lines. These results suggest that maximum cytotoxic effects can be obtained with sequential administration, but not simultaneous administration, of paclitaxel and etoposide. These findings may have important clinical implications for this combination.

Breast Neoplasms↗
PubMed1999

Effects of 4-hydroperoxy ifosfamide in combination with other anticancer agents on human cancer cell lines.

Ifosfamide is one of the currently available anticancer agents with a broad spectrum of clinical activity against a variety of tumors. To investigate its optimal combinations, we studied the effect of 4-hydroperoxy ifosfamide (the active form of ifosfamide) in combination with other anticancer agents against two human cancer cell lines, MG-63 (an osteosarcoma cell line) and MOLT-3 cells (a T-cell leukemia cell line). The cells were incubated for 4 days and 3 days, respectively, in the presence of 4-hydroperoxy ifosfamide and the other agent. Cell growth inhibition was determined by MTT assay. The effects of these drug combinations at the concentration producing 50% inhibition (IC50) were analyzed by the isobologram method. 4-Hydroperoxy ifosfamide showed additive effects with bleomycin, cisplatin, cytarabine, doxorubicin, etoposide, 5-fluorouracil, and mitomycin C, while it showed a protective effect with methotrexate in both cell lines. 4-Hydroperoxy ifosfamide showed an additive effect with vincristine in the MG-63 cell line, while it showed a sub-additive effect in the MOLT-3 cell line. No anticancer agents tested showed a supra-additive effect with 4-hydroperoxy ifosfamide. These data suggest that ifosfamide is advantageous for simultaneous administration with a majority of the anticancer agents we studied. Methotrexate is an inappropriate drug for simultaneous administration with ifosfamide.

Antineoplastic Agents, Alkylating↗
PubMed1999

Uniformity of biological effect in high-dose rate stepping source brachytherapy: an in vitro study.

In brachytherapy with a high dose rate of iridium-192, to make a flat isodose surface that covers a target volume, the dwell times of the single stepping source are computer adjusted. However, the dose rates of the irradiation vary with the positions in the volume. To examine this effect, we developed an in vitro model of stepping source brachytherapy with a 20 cm long target volume, and determined the uniformity of the biological effect in the volume on two human cancer cell lines (WiDr and A549) plated on a multi-well plate. When the source-cell distance was 10 mm, D1 (radiation dose for 1% survival) was similar in seven positions among the target volume for both cell lines. In contrast, at the 3 mm source-cell distance for one of the two cell lines (A549), D1 in the centre of the volume was significantly higher than at the periphery, suggesting a milder antitumour effect in the centre. Considering the possible decreased effect in the centre of the target volume, where most cancers clinically exhibit their maximum tumour volume, a minimum increase in radiation dose in the centre may be clinically reasonable, especially when dose reference points are set close to the source.

Adenocarcinoma↗
PubMed1999

Schedule-dependent interactions between vinorelbine and paclitaxel in human carcinoma cell lines in vitro.

Vinorelbine and paclitaxel are new anticancer agents that bind to distinct sites on tubulin and affect microtubules in opposite ways. Clinical studies of combinations of these agents have been in progress against breast cancer and some solid tumors. To clarify the optimal schedule for this combination, we studied the schedule-dependent cytotoxic effects of vinorelbine and paclitaxel against the human lung carcinoma cell line A549, the breast carcinoma cell line MCF7, the ovarian carcinoma cell line PA1, and the colon carcinoma cell line WiDr in vitro. Tumor cells were incubated with vinorelbine and paclitaxel simultaneously for both 24 h and 5 days. Cells were also incubated with vinorelbine for 24 h, followed by a 24-h exposure to paclitaxel and vice versa. Cell growth inhibition after 5 days was determined by MTT assay. The effects of drug combinations at the concentration producing 80% cell growth inhibition (IC80) were analyzed by the isobologram method (Steel and Peckham). The simultaneous exposures to vinorelbine and paclitaxel for both 24 h and 5 days produced additive effects for all four cell lines. The sequential exposure to vinorelbine followed by paclitaxel produced additive effects for the PA1 and WiDr cells, additive and antagonistic effects for the A549 cells, and antagonistic effects for the MCF7 cells. The sequential exposure to paclitaxel followed by vinorelbine produced additive effects for the A549, and PA1 cells, additive and antagonistic effects for the MCF7 cells, and antagonistic effects for the WiDr cells. Our findings suggest that the simultaneous rather than the sequential administration of vinorelbine and paclitaxel may be the optimal schedule for this combination of these two agents. Applications of this schedule dependency may be beneficial for the treatment of breast cancer and other solid tumors.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Identification and characterization of a novel UDP-GalNAc:GlcAbeta-R alpha1,4-N-acetylgalactosaminyltransferase from a human sarcoma cell line.

We recently discovered a novel alpha-N-acetylgalactosaminyltransferase in fetal bovine serum (Kitagawa et al., J. Biol. Chem., 270, 22190-22195, 1995) and also in mouse mast cytoma cells (Lidholt et al., Glycoconjugate J., 14, 737-742, 1997), which catalyzed the transfer of an alpha-GalNAc residue to the linkage tetrasaccharide-serine, GlcAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-Ser, derived from proteoglycans. In this study, we characterized this enzyme using a preparation obtained from the serum-free culture medium of a human sarcoma (malignant fibrous histiocytoma) cell line by phenyl-Sepharose chromatography. Structural characterization by1H NMR spectroscopy of the reaction product using the linkage tetrasaccharide-serine, GlcAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-Ser, as a substrate demonstrated that the enzyme was a UDP-GalNAc:GlcAbeta1-R alpha1,4-N -acetylgalactosaminyltransferase. This is the first identification of an alpha1,4-N-acetylgalactosaminyltransferase. Using N -acetylchondrosine GlcAbeta1-3GalNAc as an alternative substrate, the enzyme required divalent cations for the transferase reaction, with maximal activity at 20 mM Mn2+and exhibited a dual optimum at pH 6.5 and pH 7.4 depending upon the buffers used, with the highest activity in a 50 mM 2-( N -morpholino)ethanesulfonic acid buffer at pH 6.5. The apparent Km values obtained for N -acetylchondrosine, the linkage tetrasaccharide-serine, and UDP-GalNAc were 1060 microM, 188 microM, and 27 microM, respectively. This suggested that the linkage tetrasaccharide-serine was a good acceptor substrate for the enzyme. In addition, the enzyme utilized glucuronylneolactotetraosylceramide GlcAbeta1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4G lcbeta1-1Cer but not sulfoglucuronylneolactotetraosylceramide GlcA(3-O -sulfate)beta1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Gl cbeta1-1Cer as acceptor substrates. The possibility of involvement of this enzyme in the biosynthesis of glycosaminoglycan as well as other GlcA-containing glycoconjugates is discussed.

Animals↗
PubMed1999

SV40LT highly mutates and immortalizes two fibroblast strains from patients with Wilms' tumor.

In order to analyze in detail the process of immortalization of human cells, SV40LT was introduced into two chromosome 11p- fibroblast strains from Wilms' tumor patients. Both fibroblasts, hereafter referred to as CM1 and CM2, displayed the mutant phenotype in the crisis stage of cellular aging. In comparison to a control fibroblast, the density of the CM1 strain was abnormally high while the crisis period of the CM2 strain was abnormally long. The CM1 immortalization was 7 times greater than the control and the CM2 strain had the highest frequency of immortalization, 7 times greater than the CM1. These findings indicate that genes associated with chromosome 11p- may be involved in the immortalization of human cells. During their abnormal crisis periods, the cells derived from the patients with Wilms' tumor showed an extremely high frequency of chromosomal aberrations and mutations (6TGs --> 6TGr). These results indicate that when the growth-arrested cells from Wilms' patients are induced to grow with the introduction of SV40LT at the crisis stage they are highly mutable, resulting in their immortalization in vitro.

Antigens, Viral, Tumor↗
PubMed1999

Pharmacological properties of traditional medicines. XXV. Effects of ephedrine, amygdalin, glycyrrhizin, gypsum and their combinations on body temperature and body fluid.

Effects of ephedrine, amygdalin, glycyrrhizin, gypsum and their combinations on body temperature and body fluid were studied in rats using the method developed in our previous reports. Ephedrine significantly increased respiratory evaporative water loss and heat loss in response to a marked elevation of body temperature. There was a small but significant increase in body temperature when amygdalin was orally given rats at a dose of 46.32 mg/kg. Glycyrrhizin and gypsum were unable to affect body temperature. However, gypsum was able to prevent the increased action of ephedrine on body temperature, amygdalin exhibited a preventive tendency to it, and glycyrrhizin did not affect it. The results are in good agreement with classical claims of Makyo-kanseki-to and the related crude drugs in traditional medicine. Moreover, a combination of the four components reproduced the effects of Makyo-kanseki-to on body temperature and body fluid. This report suggests that the co-administration of ephedrine and gypsum is physiologically more desirable than ephedrine alone for dry-type asthmatic patients with a fever. Also, it experimentally supports the clinical efficacy of Makyo-kanseki-to.

Amygdalin↗
PubMed1999

Linear IgA bullous dermatosis in a patient with acute lymphocytic leukemia: possible involvement of granulocyte colony-stimulating factor.

We describe a case of linear IgA bullous dermatosis (LABD) in a patient with acute lymphocytic leukemia during treatment with granulocyte colony-stimulating factor (G-CSF). After a drug eruption due to imipenem cilastatin sodium had disappeared, bullous lesions appeared on the trunk. Results of histopathological studies and direct immunofluorescence studies of the lesion were consistent with LABD. Reinstitution of G-CSF after the resolution, however, did not reproduce the bullous eruptions. This suggests that in addition to G-CSF, the presence of precipitating factors that can synergistically enhance or accelerate the outbreak of the disease is required for the development of bullous lesions. Various cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), endogenously produced from activated lymphocytes during the drug eruption might have provided a favorable milieu for the onset of G-CSF-induced LABD. We suggest that patients with LABD will need special attention with respect to the type of cytokines or combination of cytokines given as therapeutic modalities.

Drug Eruptions↗
PubMed1999

[Successful treatment of pleuritis carcinomatosa using combination therapy of 5'-DFUR, MPA and CPA as maintenance therapy].

A 44-year-old female patient with inoperable, local advanced left breast cancer was treated with 3 cycles of high dose CAF therapy followed by combination therapy of 5'-DFUR, MPA and CPA. The patient was discharged after receiving 3 cycles of high-dose CAF therapy and continued to receive daily oral doses of 5'-DFUR (800 mg), MPA (800 mg), and CPA (100 mg) for 15 months. After 3 cycles of high-dose CAF therapy, tumor marker (CEA, CA 15-3) levels were reduced. Six months later, after 3 cycles of high-dose CAF therapy, the tumor marker levels were within the normal range. No serious side effects were observed during chemotherapy. The patient enjoyed a good quality of life. We thus confirmed that this combination regimen was effective as a maintenance therapy for local advanced breast cancer.

Adenocarcinoma↗
PubMed1999

Effect of age on rat aortic responses to acetylcholine and nitric oxide donor (NOC-18).

The purpose of the present study was to examine the effects of age on vascular responses to acetylcholine (ACh) and NO-releasing compound (NOC-18). The studies were performed in young (4 mo old, n = 8) and old (22 mo old, n = 6) male rats. Responses to ACh and NOC-18 were examined in vitro by using isolated abdominal aortic rings. The maximum relaxation response to ACh, an endothelium-dependent vasodilation, was lower in aortas from old rats. Sensitivity (mean effective concentration; EC50) of ACh in old rats was significantly less than in young rats. There were no differences in maximum NOC-18-induced relaxation, an endothelium-independent vasodilation, in aortas from young and old rats. On the other hand, the concentration-response curve for NOC-18 was shifted to the right and the sensitivity (EC50 to NOC-18) was lower in old rats. These results indicated that both endothelium-dependent vasodilation induced by ACh and endothelium-independent vasodilation induced by NOC-18 are impaired in aorta from old rats.

Acetylcholine↗
PubMed1998

Identification and characterization of HU protein from Mycoplasma gallisepticum.

A hypothetical ORF of Mycoplasma gallisepticum with a putative 99-amino-acid product (ORF99) was noted previously in the upstream region from the type II topoisomerase gene. The amino acid sequence shows weak homology with the Escherichia coli histone-like protein HU. To identify and characterize the protein product of ORF99, we prepared mouse antiserum against recombinant GST-ORF99 fusion protein. The antiserum reacted with an 11-kDa peptide in the crude cell extract of M. gallisepticum, indicating that this protein is an ORF99 product. ORF99 protein binds to DNA, although its binding affinity is weaker than that of E. coli HU. When ORF99 was cloned in a plasmid and expressed in E. coli cells depleted of HU, Mu phage growth was strongly promoted in the cells, showing the presence of HU activity. The effect of IHF mutation was suppressed when a high level of ORF99 protein was expressed in an E. coli mutant deficient in IHF.

Animals↗