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Biomedical subjects

M Morimoto

Publications and source records attributed to M Morimoto.

At least 343 records · Page 19Linked to original sources

Antitumor activity of trioxacarcin C.

The novel antitumor antibiotic, trioxacarcin C, was studied for antitumor activities against murine tumor systems. When mice with i.p.-inoculated B16 melanoma were given intraperitoneal injections of trioxacarcin C, the maximal T/C% was 164 by successive administration of 0.125 mg/kg/day (day 1 approximately 10). It also gave the prolongation of life span of mice bearing i.p. P388 leukemia (T/C 141%) by i.p. injection for 10 days, and inhibited the growth of sarcoma 180 (T/C 42%) and Lewis lung carcinoma implanted s.c. (T/C 23%) by i.v. administration for 6 or 7 days. It inhibited the growth of P388 leukemia cells in vitro and showed significant inhibition on the colony formation of HeLa S3 cells. DNA and RNA synthesis were more strongly inhibited than protein synthesis by trioxacarcin C. Also, it induced strand scission of PM-2 DNA without reducing agents or metals. It did not effect the number of white blood cells and blood urea nitrogen value of the peripheral blood.

Aminoglycosides↗

Comparative antitumor activities of 7-N-(p-hydroxyphenyl)mitomycin C (M-83) and mitomycin C.

The antitumor activity of 7-N-(p-hydroxyphenyl)mitomycin C (M-83) against 7 kinds of ascitic tumors and 4 kinds of solid tumors was compared with that of mitomycin C (MMC). M-83 showed more potent activities than MMC against ascites sarcoma 180, fibrosarcoma Meth 1, sarcoma Meth A, melanoma B-16, leukemia P388 and lymphoma EL4, by a single intraperitoneal injection. Furthermore, M-83 gave markedly higher chemotherapeutic ratio than MMC in these tumor systems. M-83 was also markedly effective against solid tumors of sarcoma 180, Meth 1, Meth A and Lewis lung carcinoma, by a single intravenous injection. M-83 gave lower myelo-suppression than MMC at the doses which gave almost equal inhibition on the tumor growth of solid Meth 1. M-83 and MMC significantly inhibited the growth of HeLa S3 cells. Cell growth was observed at 24 hours after addition of 3 X 10(-3) mM of drugs, but no growth was shown thereafter. M-83 inhibited more strongly the incorporation of the radioactive precursor into DNA than that into RNA or protein at the concentration of 3 X 10(-3) mM.

Animals↗

Immune-enhancing effect of recombinant human interferon-beta produced in Escherichia coli on human peripheral blood mononuclear cells in vitro.

Highly purified recombinant fibroblast interferon produced by Escherichia coli (ReIFN-beta) was tested for its ability to stimulate natural killer (NK) cell activity, antibody-dependent cell-mediated cytotoxicity (ADCC) and monocyte-macrophage phagocytic activity in human peripheral blood mononuclear cells (PBM) in comparison with natural human fibroblast interferon (IFN-beta). The NK cell activity against target cells (K-562, Molt-3, CCRF-HSB-2, CCRF-CEM, Daudi, and HeLa S3) was enhanced by ReIFN-beta and IFN-beta. Augmentation of cytotoxicity of NK cells was observed at a concentration of ReIFN-beta as low as 1 U/ml and increased in a dose-dependent manner. The enhancing effect of ReIFN-beta was expressed sufficiently during a 1-hr incubation with effector cells, and IFN-beta showed kinetics and potency similar to those of ReIFN-beta. ADCC was measured with chicken red blood cells (CRBC) or CCRF-CEM coated with each antibody, as target cells. Pretreatment of PBM with ReIFN-beta caused a significant increase in ADCC activity against both targets, and the enhancing activity of ReIFN-beta was similar to that of IFN-beta. Phagocytic activity of adherent cells in PBM against CRBC was enhanced by ReIFN-beta and IFN-beta as determined by microscopical cytologic examination and by the 51Cr-labeled CRBC-uptake method. From these results, it can be concluded that recombinant human IFN-beta modulates NK cell activity, ADCC and phagocytic activity of human PBM as effectively as natural human IFN-beta.

Antibody-Dependent Cell Cytotoxicity↗

Influence of surgical removal and effect of levamisole on cytotoxic T-cell-mediated antitumor immunity in mice.

In BALB/c mice bearing syngeneic fibrosarcoma Meth 1 tumors, effects of surgical removal and levamisole (LMS) on the growth of reinoculated Meth 1 cells were investigated. The growth of secondary tumors in mice with surgical removal of primary tumors was significantly inhibited as compared with that of secondary tumors in primary tumor-bearing mice without surgical removal. LMS (2.5 mg/kg) augmented the growth inhibition of secondary tumors. Its effect was significant only in mice bearing primary tumors without surgical removal. Cytotoxicity, which was detected in the spleen cells of Meth 1-bearing mice, was mediated by tumor-specific cytotoxic T-cells and augmented after surgical removal of the tumors. LMS augmented the cytotoxicity when it was administered before surgical removal of the tumors but not after surgical removal. The spleen cells of Meth 1-bearing mice in the last stage of tumor development did not exhibit cytotoxicity, but rather exhibited suppressor activity on the in vitro generation of cytotoxicity. In this stage, effect of LMS was not detected. For the induction of cytotoxic T-cells in vitro, the cooperation of nylon wool-nonadherent cells and antigen-presenting cells appeared to be necessary. Nylon wool-adherent cells exhibited the suppressor activity. LMS stimulated the activity of nonadherent cells and partially modulated the suppressor activity of adherent cells. These effects of LMS were suggested to result in the augmentation of the cytotoxicity of the spleen cells and the growth inhibition of the secondary tumors in Meth 1-bearing mice.

Animals↗

[Arteriovenous malformations of the choroid plexus--a case report].

The authors described a case of arteriovenous malformation (AVM) of the choroid plexus, and presented a review of literature. This 40-year-old male experienced a sudden onset of severe headache and vomiting on February 5th 1982. At the other hospital, CT scans revealed marked intraventricular hemorrhage, however his general condition was relatively good without a loss of consciousness, motor weakness and sensory disturbance. After about a month of conservative treatment, he was transferred to the Kochi Medical School Hospital. On admission, he had shown no neurological deficit except for slight occipital headache. Transfemoral cerebral angiography revealed an angioma of the choroid plexus, which was fed by the anterior and medial posterior choroidal arteries and drained into the internal cerebral vein. CT scans showed a small high density area due to the nidus of angioma at the interspace of bilateral frontal horns of the lateral ventricles. On March 25th 1982, using an anterior transcallosal approach, the angioma was totally removed. The histological diagnosis was AVM. The post-operative course was uneventful and the patient discharged without adding neurological deficit on April 12th 1982. Review of literature revealed 27 documented cases of angioma of the choroid plexus; 12 cases of AVM, 5 of cavernous angioma, 2 of telangiectasia, 1 of venous angioma and the other 7 of undefined description. Almost all cases were initiated with an episode of variable intracranial hemorrhage, particularly of intraventricular hemorrhage. Clinical course of them, however, were variable. On the contrast to male prevalence of AVM located in the other sites, the ratio of female to male was 2:1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Growth-inhibitory activity of recombinant human interferon-beta against cultured human cells.

The growth-inhibitory activity of recombinant human interferon-beta (ReIFN-beta) against cultured human cells was compared with that of natural human fibroblast interferon-beta (IFN-beta), and the influence of deficiency of carbohydrate on the anticellular activity was examined. The IC50 (concentration of drug required for 50% inhibition) of ReIFN-beta against 14 human cell lines was almost equivalent to that of IFN-beta, when the cells were cultured for 7 days and ReIFN-beta or IFN-beta was added on day 0 and exchanged every day from day 1 to day 6. The most sensitive cells (ICE less than 10 units/ml) were Daudi lymphoma cells and 3 melanoma cell lines, and the most insensitive cells (IC50 greater than 10(3) units/ml) were HeLa S3/IS cells (insensitive line) and CCRF-CEM leukemia cells. The other 8 cell lines were moderately sensitive to both interferons. As the intervals of exchange of ReIFN-beta or IFN-beta were extended, the growth-inhibitory activity of both interferons decreased. This phenomenon, which was more significant with ReIFN-beta than IFN-beta, was explicable in terms of the stability of both interferons incubated in the culture medium at 37 degrees. The species specificity of IFN-beta was not mediated by carbohydrate since the growth-inhibitory activity of ReIFN-beta against 2 mouse cell lines was almost equivalent to that of IFN-beta. These results indicate that the anticellular activity of ReIFN-beta was not essentially affected by deficiency of carbohydrate.

Animals↗

[Topical application of papaverine for cerebral vasospasm using prolonged release pellet--experimental studies].

Possibility of prolonged-release pellets of papaverine in the treatment of cerebral vasospasm after subarachnoid hemorrhage was investigated. Papaverine hydrochloride was enclosed in silicone tubes or mixed with silicone elastomers and polymerized. The release rate of papaverine from the silicone tubes and elastomers into a saline solution was measured for 5 weeks at 37 degrees C and at room temperature. Although the volume of released papaverine was extremely large in the first two days, a constant release rate was maintained until the 35th day in vitro for both types of pellets. The daily amount of released papaverine was 1.5 to 3.0 x 10(-2)/day, and 1 to 4 x 10(-6)/day of original volume from silicone elastomers and tubes, respectively, at 37 degrees C. The release rate at 37 degrees C was 10 times as high as at room temperature. When the silicone elastomers were applied, the rate was well correlated with the surface area of the pellets, and was measured as 2.5 to 5.0 x 10(-5)/day/mm2 of the original volume. It means that when a pellet of 4 mm in diameter x 45 mm in length (a surface area of 600 mm2) is applied, 61.7% of the papaverine is released from the pellet during the first 2 weeks. Neither adverse reaction or intracranial histological abnormality was noted in vivo during the 40-day observation period using a dog, in which two pellets containing 275 mg and 297 mg of papaverine were subcutaneously implanted, and a pellet containing 275 mg of papaverine intracranially.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Diagnosis of left atrial masses by computed tomography: with special reference to the differentiation between mural thrombi and myxomas].

Computed tomographic features of left atrial mural thrombi were compared with those of left atrial myxomas using a third generation system. In seven of 23 patients with mitral valvular disease, computed tomography (CT) demonstrated a total of 12 left atrial mural thrombi. There was calcification in about one-third of the thrombi and marked calcification of the mitral valve in all the seven cases. Mean CT value of the 12 thrombi ranged from +17.5 to +89.8 Hounsfield units (HU) (average +44.5 HU), and in only one it was below +20 HU. All thrombi appeared to be heterogeneous and irregular in shape such as elliptic, triangular or flat on cross-sectional tomogram. In addition, reconstructed coronal and sagittal imagings from serial CT images were very useful for localizing the calcification in the thrombi and determining the site of the attachment of the thrombi to the atrial wall. On the other hand, calcification of the tumor or mitral valve was not detected in two patients with left atrial myxomas by CT. The mean CT value of myxoma was averaged +30.2 HU, which was lower than that of thrombi. Both myxomas were ovoid in shape and appeared to be homogeneous in CT images. ECG gated CT revealed pendular movement of the tumor which prolapsed through the mitral orifice into the left ventricular inflow tract during diastole and backed into the left atrium during systole, although it was slightly difficult to detect the site of the attachment of the tumor. In conclusion, we should evaluate appearances, calcification of the mitral valve, mean CT value, shape and movement in the computed tomographic diagnosis of left atrial masses. In consideration of these characteristic findings, differentiation between mural thrombi and myxomas could be made.

Adult↗

Pulmonary varices associated with mitral valve disease: a case report and survey of the literature.

A case of pulmonary varices in a 24-year-old man with mitral regurgitation is reported. A brief summary of the literature on pulmonary varices associated with mitral valve disease is presented, with special reference to its etiology and surgical treatment. It is strongly suggested that production of varicosities of the pulmonary vein requires not only increased pulmonary venous pressure but also other local factors. If the patient has symptoms due to mitral regurgitation, operation for mitral valve disease is indicated. Direct operative intervention for the varices should not be performed.

Adult↗

Chemo-immunotherapy of methylchoranthrene-induced fibrosarcoma by concanavalin A-bound tumor vaccine, levamisole and mitomycin C.

Concanavalin A (ConA)-bound-tumor cell vaccine of methylchoranthrene-induced fibrosarcoma (Meth 1) induced tumor-specific immunoprophylactic and immunotherapeutic response against an inoculum of live Meth 1 cells in histocompatible animals. ConA-free Meth 1 vaccine induced much less response under the identical experimental conditions. Immunotherapeutic potency of ConA-bound Meth 1 vaccine was enhanced by levamisole, and 37% of the animals inoculated with 10(4) live Meth 1 cells at day 0 were cured when they were administered 10(6) cells of ConA-bound Meth 1 vaccine at days 1 and 8 and 0.63 mg/kg levamisole at days 1,2 and 3. Delayed administration of levamisole at day 8,9 and 10 was less effective than the earlier administration, but still produced a 17% cure of Meth 1-bearing animals when combined with ConA-bound Meth 1 vaccine. Immunotherapeutic response under these regimens was further enhanced by mitomycin C, and approximately 60% of the animals inoculated with 10(5) Meth 1 cells were cured when three agents were administered at the defined intervals. These results suggest the feasibility of the regimen in which the therapeutic response induced by immunotherapeutic agents is further enhanced by the selected chemotherapeutic agents.

Animals↗

Tetrocarcins, new antitumor antibiotics. 3. Antitumor activity of tetrocarcin A.

Tetrocarcin A, isolated from a Micromonospora culture showed activity against experimental i.p. inoculated tumors such as Ehrlich carcinoma, MH134 hepatoma, B16 melanoma. But it was not active against solid tumors such as sarcoma 180 and Ehrlich carcinoma. It was marginally active against the growth of solid Lewis lung carcinoma without prolonging the life span of the tumor-bearing mice. It was active against P388 leukemia (i.v.-i.v. system). It did not show myelosuppression and nephrotoxicity in mice. DNA and protein synthesis of P388 cells in culture were more significantly suppressed than RNA synthesis by tetrocarcin A.

Aminoglycosides↗

The action of 7-N-(p-hydroxyphenyl)mitomycin C [M-83] in suppressing murine immune response.

The immuno-suppressive activities of 7-N-(p-hydroxyphenyl)mitomycin C [M-83], a derivative of mitomycin C (MMC), which has better antitumor activity against murine tumors, was investigated in mice. A single injection of M-83 induced an apparent but relatively transient reduction in both plaque-forming cell production and delayed type hypersensitivity reaction to sheep red blood cells. The suppressive effect of M-83 was significantly milder than that of MMC at the same effective and molar equivalent doses. Moreover, the recovery from immunosuppression induced by M-83 was also relatively rapid as compared with MMC. The inhibiting activity of M-83 against the blastogenic response of spleen cells was milder in vivo, but was more significantly cytotoxic in vitro than that of MMC.

Animals↗