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Biomedical subjects

K Morikawa

Publications and source records attributed to K Morikawa.

At least 325 records · Page 18Linked to original sources

[Measurement of neutrons from an electron accelerator by rem-counter].

In the measurement of neutrons from the medical electron accelerator by a rem counter, two problems disturb accurate measurements. One is the pile-up of signals produced by X-rays during each X-ray burst and the other is the increased counting loss caused by bunched nature of yielded neutrons. The time spectrum of neutrons measured by the rem counter 2202 D (manufactured by Studsvik) rises up to a maximum value by about 20 microseconds and then falls down exponentially with a time constant of about 90 microseconds. On the other hand, that of X-rays is roughly rectangular with several microseconds width. A time discriminating system was prepared to be combined with the rem counter, which was triggered by leading edge of electron beam pulses, rejected pile-up signals due to X-ray bursts, and counted pulses of neutrons in a specified time window. The system discriminated the pile-up enough to measure neutrons at a X-ray dose rate of at least 30 mGy/h. Nonparalyzable counting loss correction was practicable upto about 10 mSv/h for the beam pulse rate of 85 Hz, in which the dead time of the rem counter was estimated as 4 microseconds.

Neutrons↗

Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice.

We have ascertained previously from a study of fully allogeneic irradiation chimeras in mice that the H-2 restriction of the suppressor factor (Ly-2 T suppressor factor) is determined by the post-thymic environment protected by the donor cells, rather than by the thymic environment of the recipient. In the present study, we analyzed differentiation influences that determine the Igh restriction specificities of the suppressor inducer T cell factor(s) (TsiF) that are produced by Ly-1+ splenic T cells in fully allogeneic bone marrow chimeras in mice. AKR mice that had been lethally irradiated and reconstituted with B10 marrow cells, [B10----AKR] chimeras, produced Ly-1 TsiF after hyper-immunization with sheep erythrocytes (SRBC) which suppressed antigen--specifically the primary antibody responses to SRBC that were generated in cells of the same Igh-Vb haplotype of donor strain and not those generated in cells of the recipient Igh-Va type. Similar results were obtained when Ly-1 TsiF from [B6----BALB/c] and [BALB/c----B6] chimeras were analyzed. Furthermore, the Ly-1 TsiF from [BALB/c----B6] chimeras suppressed the primary antibody responses of both BALB/c [H-2d, Igh-Va, Igh-Ca] and BAB-14 (H-2d, Igh-Va, Igh-Cb), but not those of CAL-20 (H-2d, Igh-Vd, Igh-Cd). These results demonstrate clearly that the Ly-1 TsiF from allogeneic bone marrow chimeras are donor Igh-V-restricted and are not influenced by the recipient micro-environment, presumably that provided by the thymuses of the recipient mice.

Animals↗

Host-mediated therapeutic effects produced by appropriately timed administration of bleomycin on a rat fibrosarcoma.

The timing of bleomycin (BLM) administration after KMT-17 tumor inoculation was found to be important for optimizing its therapeutic effect on tumor-bearing rats. A remarkable therapeutic effect was observed when BLM (5 mg/kg/day) was administered i.p. for 5 days from the eighth day after tumor inoculation (Day 8 to Day 12) rather than when BLM was administered i.p. for 5 days during the days immediately following tumor inoculation (Day 1 and Day 5) (cured rats/treated rats: 10/21 and 2/16, respectively). By means of a Winn assay, stronger tumor-neutralizing activities were observed in spleen cells from BLM (Day 8 to Day 12)-treated tumor-bearing rats than were observed in spleen cells from BLM (Day 1 to Day 5)-treated tumor-bearing rats (% Inhibition: 70.9 and 49.3%, respectively). These therapeutic effects were thus found to be consistent with the antitumor immunity against KMT-17. The enhanced tumor-neutralizing activities of spleen cells from BLM-treated tumor-bearing rats were suppressed by adding spleen cells from nontreated tumor-bearing rats. In cell transfer experiments, an antitumor transplantation resistance in rats immunized with irradiated KMT-17 cells was abrogated by an adoptive transfer of spleen cells from untreated tumor-bearing rats or BLM (Day 1 to Day 5)-treated tumor-bearing rats but not from BLM (Day 8 to Day 12)-treated tumor-bearing rats. These results suggest that, when BLM is administered during a late stage of tumor growth, it is effective in eliminating suppressor cells and that this leads to an improvement in the therapeutic effects of the drug.

Animals↗

Hydrogen peroxide as a tumoricidal mediator of murine polymorphonuclear leukocytes induced by a linear beta-1,3-D-glucan and some other immunomodulators.

Polymorphonuclear leukocytes (PMN) of mice can destroy tumor cells effectively in vitro in the presence of antitumor polysaccharide, linear beta-1, 3-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 (TAK), and some other immunomodulators. In the present study, we investigated the mechanism of the tumoricidal activity of PMN induced by these immunomodulators and especially TAK. The TAK-induced PMN cytotoxicity was concluded to involve hydrogen peroxide from the following results: (a) the cytotoxicity depended on glucose consumption; (b) it was almost completely inhibited by catalase but not affected by superoxide dismutase; (c) it was not reduced by cyanide or azide, which are inhibitors of myeloperoxidase; (d) it was not affected by scavengers of singlet oxygen or hydroxyl radical; (e) release of hydrogen peroxide from PMN was observed by the addition of TAK; (f) MM46 target cells were lysed directly by hydrogen peroxide in the absence of myeloperoxidase; (g) the supernatant of PMN in the presence of TAK, tested as a stable cytotoxic factor, did not have cytotoxic activity, and protease inhibitors had no effect on this cytotoxicity. These results suggest that hydrogen peroxide is a direct cytotoxic mediator in TAK-induced PMN cytotoxicity. Next, the mechanism of PMN cytotoxicities induced by other immunomodulators was also examined and was compared with that induced by TAK. The results suggest that hydrogen peroxide is also important for these cytotoxicities whereas, unlike the results with TAK, the H2O2:halide:myeloperoxidase system may partly participate in the cytotoxicities with some immunomodulators.

Adjuvants, Immunologic↗

Analysis of contact sensitivity to 2,4-dinitrofluorobenzene (DNFB) in allogeneic bone marrow chimaera in mice.

Irradiated C57BL/6 (B6) and C3H mice were reconstituted with bone marrow cells from BALB/c mice. The chimaeric mice, [BALB/c----B6] and [BALB/c----C3H], developed and expressed contact sensitivity to DNFB. The in vivo responses paralleled to proliferative responses of regional lymph node cells of the chimaeras to DNBS in vitro. Furthermore, intravenous administration of DNBS rendered the chimaeras tolerant to subsequent sensitization with DNFB. The tolerance was transferred to lightly irradiated BALB/c mice by the spleen and lymph node T cells. These results represent marked contrast to our previous observations that [B6----C3H] and [B6----AKR] chimaeras were unable to develop specific unresponsiveness to stimulation with DNFB by the intravenous route. The controversial observations seen in the chimaeras prepared by BALB/c bone marrows and those prepared by B6 cells are discussed.

Animals↗

Induction of tumoricidal activity of polymorphonuclear leukocytes by a linear beta-1,3-D-glucan and other immunomodulators in murine cells.

The cytotoxic activity of polymorphonuclear leukocytes (PMN) against tumor cells induced in vitro by antitumor immunomodulators was examined by a 51Cr release cytotoxicity assay. Among 28 immunomodulators and other agents thus far tested, only beta-1,3-glucan from Alcaligenes faecalis var. myxogenes IFO 13140, Bacillus Calmette-Guérin, Propionibacterium acnes, zymosan A, and Nocardia cell wall skeleton were found to cause induction. The cytotoxic activity of PMN with the beta-1,3-glucan was very high, almost 100% cytolysis being observed at an effector:target ratio as low as 3. The other four potent immunomodulators had effects very similar to that of the beta-1,3-glucan. All five tumor cell lines tested, MM46, MM48, MH134, EL-4, and YAC-1, were lysed, whereas normal spleen and thymus cells and PMN were not. Of four types of effector cells tested, PMN and casein-induced macrophages were effective, whereas resident macrophages and J774 cells were not effective. The cytotoxic activity of PMN was greater than that of induced macrophages, although both were induced by casein. From results on the polysaccharides tested, a linear beta-1,3-glucan structure and a minimum number average degree of polymerization of 125 of the beta-1,3-glucan seemed to be required for induction of cytotoxicity of PMN. The cytotoxic features of PMN and possible chemical structures of antitumor polysaccharides for induction of cytotoxicity are discussed.

Adjuvants, Immunologic↗

Antitumor activity of D-mannosamine in vitro: cytotoxic effect produced by mannosamine in combination with free fatty acids on human leukemia T-cell lines.

Cytotoxic effects of mannosamine and free fatty acids on human malignant T-lymphoid cell lines derived from patients with T-cell leukemia were investigated. The combination of mannosamine and an unsaturated fatty acid (oleate or linoleate) produced more striking cytotoxic effects on malignant lymphoid cells than on normal human lymphocytes. The amino sugars glucosamine or mannosamine in the combination caused a synergistic cytotoxic effect, while the other carbohydrates (N-acetylmannosamine, N-acetylglucosamine, or mannose) had little effect. On the other hand, the effect of saturated fatty acids (palmitate or stearate) in the same system was nil. An unsaturated fatty acid (oleate) caused an increase in lipid fluidity of the surface membrane in MOLT-4 lymphoid cells, which possess higher lipid fluidity in combination with mannosamine, while saturated fatty acids had no effect on the fluidity properties of the membrane lipids (even in the presence of mannosamine). The relationship between mannosamine and unsaturated fatty acids in cytolysis was discussed.

Carbohydrates↗

Enhancing effect of quercetin on 3-methylcholanthrene carcinogenesis in C57Bl/6 mice.

We investigated the effect of quercetin on 3-methylcholanthrene (MCA) carcinogenesis in C57Bl/6 mice. We found that quercetin itself was not carcinogenic when administered i.m., even at a dose of 20 mg, throughout an observation period of 420 days. An i.m. administration of various doses of quercetin admixed with 1.0 mg of MCA, however, significantly shortened the mean latency periods for the development of local primary tumors compared with those of the group which had been given MCA alone. The shortening of latency periods was also found in the experiments using 0.1 mg of MCA after the administration of quercetin either admixed with MCA or fed with a diet containing it. Moreover, lung metastasis increased in mice given the mixture of MCA (0.1 mg) and quercetin compared with its occurrence in mice given MCA alone. A simultaneous administration of MCA and quercetin significantly increased the in vivo sister chromatid exchanges (SCE) formation of bone marrow cells when compared with its occurrence in the group given MCA alone. These results suggest that quercetin has an enhancing effect on MCA carcinogenesis and that this enhancement may be associated with such a genetic effect as an increased mutation rate in the host.

Animals↗

[Augmentation of antitumor immune responses by the antitumor antibiotic bleomycin].

We investigated the augmentation of antitumor immune responses by the antitumor antibiotic, bleomycin (BLM). BLM augmented immune responses against tumor cells, such as transplantation resistance and tumor cell-neutralizing activity of spleen cells, in rats immunized with the tumor cells or bearing the tumor as a result of selective elimination of immune-suppressor cell activities. Moreover, BLM was able to activate macrophages as an effector of antitumor resistance. We observed good correlation between the therapeutic effects of BLM and the above immune augmentation when tumor-bearing rats were treated with the drug. These results suggest that the chemotherapeutic action of BLM partially depends on a host-mediated effect, i.e., antitumor immune responses augmented by the drug.

Adjuvants, Immunologic↗

Various types of 5s rRNA crystals as studied by X-ray diffraction and electron microscopy.

Six different types of 5 S rRNA crystals were obtained using the specimen purified from highly thermophilic bacteria, Thermus thermophilus HB8. The best crystal available diffracts X-rays up to 13A Bragg spacing. One type of crystals was sufficiently thin to be subjected to electron microscopy. Optically filtered images of two different projections exhibit molecular regions distinctly from the medium. Preliminary investigation of packing of the molecules into the unit cell gives some implication of their overall shape.

Microscopy, Electron↗