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Biomedical subjects

I Kaneko

Publications and source records attributed to I Kaneko.

At least 73 records · Page 4Linked to original sources
PubMed1989

DNA-lesion and cell death by alpha-particles and nitrogen ions.

When the natural logarithm of the surviving fraction is plotted against the dose of radiation, curves with shoulders at relatively high survival levels are obtained after gamma-rays. The curves were practically linear in case of HMV-I and HA-1 cells irradiated by charged particle beams. These cells were derived from human malignant melanoma and Chinese hamster cells, respectively. The amount of DNA single strand breaks (ssb) by gamma-rays or nitrogen-ions (LET=530KeV/micrometers) in HMV-I cells increases linearly with increment in dose, when the ssb is detected using the alkaline elution technique. There is no close relationship between the dose-response curve of the ssb and the dose-survival curves after gamma-rays or N-ions. The amount of DNA double strand breaks (dsb) by gamma-rays increases quadratically with increment of dose, in both HMV-I cells and HA-1 cells, when the dsb is detected using the neutral elution technique. The survival fraction for HA-1 cells is slightly higher than that for HMV-I cells, at the same dose, and the amount of dsb for HA-1 cells is considerably greater than that for HMV-I cells. These results suggest that the radiosensitivities to gamma-rays in different cell lines do not correspond to the number of DNA strand breaks. The amount of both non-repairable ssb and dsb also increases quadratically with increment of dose for gamma-rays and almost linearly with increment of dose for N-ions and alpha-particles (LET=36keV/micrometers for HA-1 cells and LET=77keV/micrometers for HMV-I cells). The dose-response curves for non-repairable dsb in case of these radiations seemed to mirror image the dose-survival curves for these radiations, in both cell lines. The number of non-repairable DNA strand breaks in the two cell lines, at the same level of survival was much the same. These results show the close relationship between the induction of non-repairable DNA strand breaks and cell killing.

Alpha Particles↗
PubMed1989

Influence of alpha-chloralose on muscle relaxant effect of chlorzoxazone in rats and pharmacodynamic analysis.

The Pharmacological response intensity of chlorzoxazone (CZX) was measured by the crossed extensor reflex (CER) method in anesthetized rats. The appropriate dose of alpha-chloralose (ACH) was examined to bring about a quantitative effect of CZX. The pharmacodynamics of CZX was also characterized in the anesthetized rats at three different doses of CZX. When rats were anesthetized with ACH at three different doses (80, 110, and 150 mg/kg i.p.), the CER response caused by CZX at the doses of 25, 50, and 75 mg/kg p.o. was depressed dose-dependently. Among these three different doses of ACH, 80 and 110 mg/kg gave similar results in describing the pharmacological response induced by CZX with time, whereas a dose of 150 mg/kg of ACH elicited a stronger and longer CZX response than the other two doses. The area under the intensity-time curve also showed the same tendency. These findings suggested that the dose size ranging from 80 to 110 mg/kg of ACH for surgical anesthesia was appropriate to evaluate the quantitative pharmacological response of CZX. Pharmacodynamic analysis offered the results that the dose-normalized biophase levels of CZX were coincident with each other when CZX was given at three different doses under ACH anesthesia at the dose of 80 mg/kg. This suggested that the disposition of CZX in rats obeyed linear kinetics and the theoretical values of CZX-induced response would be predictable. This implied that pharmacological response intensity of CZX was reasonably related to the relative biophase CZX level via Hill's equation.

Animals↗
PubMed1989

Complestatin, a potent anti-complement substance produced by Streptomyces lavendulae. I. Fermentation, isolation and biological characterization.

A new potent inhibitor of complement system, named complestatin, was isolated from the mycelium of Streptomyces lavendulae SANK 60477. Complestatin (C61H45N7O15Cl6, MW 1,325) was a peptide compound having two unusual amino acids, D-(-)-4-hydroxyphenylglycine and D-(-)-3,5-dichloro-4-hydroxyphenylglycine. This compound inhibited the hemolysis of sensitized sheep erythrocytes (EA) mediated by guinea pig and human complement 50% at concentrations of 0.4 and 0.7 micrograms/ml, respectively, but did not trypsin and alpha-chymotrypsin activities at 200 micrograms/ml. When complestatin was administered intravenously to the sensitized guinea pigs, it strongly inhibited the systemic anaphylactic shock elicited by the antigen probably by blocking generation of anaphylatoxins (C3a and C5a).

Amino Acids↗
PubMed1989

Neoplastic cell transformation by heavy ions.

We have studied the induction of morphological transformation by heavy ions. Golden hamster embryo cells were irradiated with 95 MeV 14N ions (530 keV/microns), 22 MeV 4He ions (36 keV/microns), and 22 MeV 4He ions with a 100-microns Al absorber (77 keV/microns) which were generated by a cyclotron at the Institute of Physical and Chemical Research in Japan. Colonies were considered to contain neoplastically transformed cells when the cells were densely stacked and made a crisscross pattern. It was shown that the induction of transformation was much more effective with 14N and 4He ions than with gamma or X rays. The relative biological effectiveness (RBE) relative to 60Co gamma rays was 3.3 for 14N ions, 2.4 for 4He ions, and 3.3 for 4He ions with a 100-microns Al absorber. The relationship between RBE and linear energy transfer was qualitatively similar for both cell death and transformation.

Animals↗
PubMed1988

Pharmacodynamics of chlorzoxazone in rats.

Pharmacological effect-time profiles of a centrally acting muscle relaxant, chlorzoxazone, were evaluated by both rotarod and crossed extensor reflex (CER) methods. Drug response was measured by percent change in the remaining time on the rod for the former method and in intensity of isometric contraction of the muscle for the latter method. The drug response was quantitated using the logarithmic-logistic function and then biophase levels were calculated. The results indicated that the maximum response was observed 10 min after drug administration for both methods at every dose studied. However, the values of ED50 indicated that the CER method was more sensitive than the other. Pharmacodynamic analysis offered the results that the dose-normalized biophase levels for each dose obtained from the CER method were coincident with each other and that the logarithmic-logistic function was proven to be of use for the pharmacodynamic modeling which could simply assess the bioavailability. On the other hand, all dose-normalized values obtained from the rotarod method did not scatter around the same line. This evidence indicated a violation of assumption for the pharmacodynamic analysis. From the above data, the CER method proved to be of use for assessing the drug response based on the dose-independent kinetics with high sensitivity.

Animals↗
PubMed1988

Treatment of brain tumors with iridium-192 seeds.

Interstitial radiation therapy of brain tumors requires positioning of the radioactive sources with good precision in order to achieve a sufficient dose in the tumor without too much damage to surrounding tissues. A method for application of 192Ir seeds in brain tumors is described and preliminary results in seven patients reported. The method, which uses CT-guided stereotactic localization and computerized dose planning, is at present fairly complicated. The preliminary results are promising and no serious complications have so far been observed.

Adult↗
PubMed1988

Effect of membrane trapping in plasma fractionator on separative characteristics.

Several kinds of plasma fractionators have been introduced to actively separate protein fractions between albumin and globulins in double filtration plasmapheresis. However, relatively large molecular weight proteins are known to be partially trapped by the membrane in a plasma fractionator. In this paper, effects of membrane trapping on separation characteristics in plasma fractionators were examined during in vitro and in vivo studies. All in vitro experiments were done with a closed circuit under constant-flow rate filtration. Protein concentration in feed tank kept constant at no filtration in AS-14H, Evaflux 4A and 2A, while 20-40% of IgG and 40-60% of beta-lipoprotein in 2 liter plasma were removed by membrane trapping for 300 min when filtration fraction equaled 0.87. Protein plugging to the membrane seems to be a major factor in these proteins. And, Dead-end and Partially Discarded modalities with relatively high filtration fraction are effective for the separation between albumin and globulin. Twenty-seven DFPP treatments in 13 patients with autoimmune diseases were done to allow us to estimate the effects of membrane trapping during an in vivo study. All treatments using 6 types of plasma fractionator were performed under constant operating conditions with Partially Discarded modality. In any plasma fractionator, beta-lipoprotein was fairly trapped at 30 min after the start of treatment.

Adsorption↗
PubMed1987

Induction and repair of DNA lesions in cultured human melanoma cells exposed to a nitrogen-ion beam.

Induction and repair kinetics of DNA lesions after exposure to nitrogen ions (N-ions) were studied in comparison to those after 180 kVp X-rays. DNA lesions in human melanoma cells (HMV-I) irradiated with 95 MeV N-ions (0-6 Gy, l.e.t.D = 530 keV micron-1 or with X-rays (0.9 Gy) were assayed by alkaline elution. The N-ion r.b.e. for DNA lesion induction was approximately 0.7. About 85 per cent of the lesions induced by N ions were rejoined with a time-course similar to the rejoining of DNA lesions produced by X-rays. These lesions were considered to be induced by delta-rays around the N-ion tracks. The fraction of residual DNA lesions remaining after a 6 h post-irradiation incubation was higher for N-ions than for X-rays. Unlike the case for X-rays, DNA-protein crosslinks were included in the residual DNA lesions after N-ion irradiation.

Cells, Cultured↗
PubMed1987

A comparative study on proteins released from metaphase chromosomes after digestion with restriction endonucleases and deoxyribonuclease I.

Extensive digestion of Chinese hamster metaphase chromosomes with Alu I, Hae III and Hinf I released up to 40 distinct chromosomal proteins. Some of the proteins released by Hae III or Hinf I were enriched in the protein moiety liberated by Alu I but several proteins released by Hae III were not released by Alu I digestion. The amount of chromosomal protein released by deoxyribonuclease I (DNase I) was comparable to that liberated by the three restriction enzymes so far tested, while only four abundant protein species were detectable in the protein moiety released by DNase I. Two of them with molecular weights of 58,000 and 50,000 were also released by the three restriction enzymes and are similar in size to those found previously in the core-like structure of histone-depleted chromosomes.

Animals↗
PubMed1986

Purification and characterization of adenine phosphoribosyltransferase from mouse mammary carcinoma FM3A cells in culture.

Adenine phosphoribosyltransferase has been purified to apparent homogeneity from mouse mammary tumor FM3A cells. The purified enzyme, with a specific activity of 20.6 X 10(6) units/g protein at 30 degrees C, was homogeneous as judged by polyacrylamide gel electrophoresis and Ouchterlony double immunodiffusion analysis. The native enzyme had a molecular weight of 44,000 and a subunit composition of 23,000. Apparent Km values for adenine and 5-phosphoribosyl-1-pyrophosphate (PRib-PP) were 6.6 microM and 1.2 microM, respectively. Free Mg2+ was an essential activator with a half-maximal effect at 0.4 mM. AMP was an inhibitor, competitive with PRib-PP, and the Ki value was estimated to be 24 microM. The enzyme activity was not significantly affected by 2,6-diaminopurine, 4-carbamoylimidazolium 5-olate, 8-azaadenine, and 2-fluoro-6-aminopurine. An antibody against the purified mouse adenine phosphoribosyltransferase was raised in a rabbit. The enzyme derived from either mouse, Chinese hamster, or human cells was completely neutralized and precipitated by this antibody, indicating that these enzymes share a common antigenic determinant.

Adenine Phosphoribosyltransferase↗
PubMed1986

DNA fragments of 300 base pairs released from metaphase chromosomes by digestion with deoxyribonuclease I.

DNase I digestion of metaphase chromosomes, that have been extensively digested with Hae III, further released chromosomal DNA and proteins; 3.3% and 10.8% of the chromosomal DNA and proteins, respectively, remained insoluble. However, digestion of chromosomes first with DNase I followed by Hae III caused most of the proteins to remain in the insoluble fraction. DNase I released DNA fragments of 300 base pairs long which were not released by Hae III digestion. These DNA fragments may be protected by protein components from further fragmentation by DNase I.

Animals↗