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Biomedical subjects

E Tsubura

Publications and source records attributed to E Tsubura.

At least 37 records · Page 2Linked to original sources
PubMed1988

[Restorative effect of muroctasin, MDP-Lys (L 18), on leukopenia caused by anticancer chemotherapy in lung cancer--comparative study by envelope method].

Muroctasin, a derivative of MDP, is known to augment the number of WBC via colony-stimulating factor. Muroctasin has been expected to be promising for application to leukopenia caused by anticancer chemotherapy. When WBC decreased to less than or equal to 3,000/mm3 after the 1st course of chemotherapy, 131 patients with lung cancer, who were previously classified by chemotherapy combination, were enrolled in the study and randomized into 3 groups, 200 micrograms (H), 100 micrograms (L) and untreated control (C) groups. The patients were then subcutaneously treated once daily for 6 consecutive days. WBC and its differential count were measured on days 4, 7 and 15 after commencement of the study. WBCs in H and L groups showed greater recovery than in C group. In WBC differential count, the recovery of neutrophil was prominent in muroctasin-treated groups. A portion of immature neutrophil in bone marrow was also increased by muroctasin treatment. In the present study, the usefulness of muroctasin in leukopenia was indicated when administered at dosages of 200 micrograms for 6 days.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Restorative activity of muroctasin on leukopenia associated with anticancer treatment.

The restorative effect of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a muramyl dipeptide derivative, was studied in patients with leukopenia associated with anticancer chemotherapy and radiation therapy. The drug was subcutaneously administered to 102 cancer patients in a single doses of 200 or 400 micrograms, and each dosage was given either every day for 6 days or every other day over a 5-day period. White blood cell (WBC) counts were made before, during and after treatment. MDP-Lys(L18) was most effective in patients receiving the drug every day and the 400 micrograms dose was somewhat superior to the 200 micrograms dose in augmenting the WBC population. Overall, the response to MDP-Lys(L18), in terms of the increase in number of WBCs, was good to excellent in 41.6% of patients. MDP-Lys(L18) was considerably more effective in patients with solid tumors than in those with hematological malignancies. The most common side effect was fever, which was dose-dependent, more pronounced with alternate-day dosing, and generally well controlled with antipyretics. The results of this study indicate that MDP-Lys(L18) is useful in improving the WBC count in leukopenic cancer patients treated with anticancer therapy. Considering the efficacy and side effect profiles together, it is suggested that 200 micrograms/day for 6 consecutive days is the optimal treatment regimen.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Antipyretic activity of a human immunoglobulin preparation for intravenous use in an experimental model of fever in rabbits.

In an effort to elucidate the reason that fever in patients with severe bacterial infections subsided in some cases after the administration of human immunoglobulin preparations for intravenous use (IGIVs), we focused our attention on the antipyretic activity of IGIVs by investigating experimentally produced pyrexia in rabbits with Escherichia coli-derived lipopolysaccharide (LPS). Although little difference in antibody titers against the antigens composing molecules of LPS was found among the IGIVs that were used, IGIVs treated at pH 4 were demonstrated to inhibit a strongly LPS-induced second-phase febrile response, whereas the inhibitory effect of sulfonated and pepsin-treated IGIVs was weak. In vitro experiments on interleukin-1 production by rabbit macrophages stimulated with LPS, silica gel or latex beads and on rosette formation showed that these functions of the cells were also inhibited by IGIVs. The in vivo antipyretic activity and the results of the two in vitro experiments correlated closely. The inhibitory potency decreased in the following order: immunoglobulin G (IgG) treated at pH4, sulfonated IgG, and pepsin-treated IgG. Thus, it is possible that the subsidence of LPS-induced fever by IGIVs was mediated by inhibition of interleukin 1 production by means of binding of IgG to macrophages via an Fc receptor. Results of this study also indicated the importance of the structural integrity of the Fc portion of the IgG contained in the IGIVs to bind with its receptor on the macrophage so as to influence the various functions carried out by the cell.

Animals↗
PubMed1986

Activation of antitumor properties in alveolar macrophages from protein-calorie malnourished rats.

Protein-calorie malnutrition (PCM) was induced by feeding male F344 rats on a 5% casein diet for 7 weeks. At appropriate times, rats from control (20% casein diet) and PCM groups were killed and alveolar macrophages (AM) were obtained by bronchoalveolar lavage. The functional integrity of the AM was determined by measuring their ability to become tumoricidal on treatment with macrophage activators, such as muramyl dipeptide (MDP) or multilamellar liposomes containing MDP or its lipophilic analog, MTP-PE. After 5 and 7 weeks, the numbers of lavaged AM per gram body weight of rats were much higher in the PCM group than in the control group. In week 3, AM from the PCM group showed spontaneous tumoricidal activity against syngeneic tumor cells, but in weeks 5 and 7 they did not. However, AM from PCM rats behaved the same way as controls in their response to activation stimuli in vitro with multilamellar liposomes containing synthetic MDP or MTP-PE. These data show that PCM affects the number of AM, but that AM from rats in a state of PCM become tumoricidal in response to activation stimuli in vitro.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Effect of a thymic factor, thymostimulin, on growth and pulmonary metastases of Lewis lung carcinoma.

The antitumor and antimetastatic activities of a thymic factor, thymostimulin (TP-1), with or without cyclophosphamide (CPA) were examined in C57BL/6 mice inoculated with Lewis lung carcinoma (3LL). Tumor growth was followed by determining the tumor diameter after tumor implantation. TP-1 given to mice every 2 days after tumor implantation significantly inhibited tumor growth without affecting the survival rate. For induction of spontaneous pulmonary metastases, 3LL cells were implanted into the footpads of mice, and the implanted tumor was removed on day 9. The antimetastatic effect of TP-1 on pulmonary metastases after removal of the primary tumor was evaluated by counting the number of pulmonary surface nodules. TP-1 showed antimetastatic activity depending on its time of administration and dose. Combined therapy with TP-1 plus CPA significantly prolonged the survival of mice with pulmonary metastases. The cytolytic activities of spleen cells on 3LL cells were enhanced in mice treated with TP-1 and/or CPA and the cytolytic activity of nonadherent spleen cells, the T-cell population, was enhanced. The role of cytolytic spleen cells in inhibiting and preventing metastases was discussed.

Animals↗
PubMed1985

Comparison of cell profiles of bronchial and bronchoalveolar lavage fluids between normal subjects and patients with idiopathic pulmonary fibrosis.

The cell profiles of bronchial and bronchoalveolar lavage fluids (BLF and BALF) of patients with idiopathic pulmonary fibrosis (IPF) were compared with those of normal volunteers (NV) and age-matched control patients (CP), to characterize the cell profiles of the bronchoalveolar region in normals and patients with IPF. In BALF of nonsmokers from both control groups (NV and CP), alveolar macrophages (AM) were predominant and the percentage of neutrophil leukocytes and that of eosinophil leukocytes below 1% of the total cells. The percentage of neutrophils and that of bronchial epithelial cells were higher in BLF than in BALF of both control groups. Of the immune and inflammatory cells in BLF, the mean percentage of neutrophils was 12% in NV group and 42% in CP group. The percentage of neutrophils and that of eosinophils in BALF were higher in IPF group than in CP group, but the percentage of neutrophils in BLF of IPF group was comparable to that of CP group. In the IPF group, the percentage of neutrophils in BALF was lower than that in BLF. These results indicated that even in healthy subjects, a considerable number of neutrophils are present in the bronchial region and that the cell profile of the lavage fluid of the bronchoalveolar tree changes depending on the method of lavage. Presumably the higher percentage of neutrophils in BALF of patients with IPF is partly due to derangements of the alveolar structure, because the amount of saline infused into this region is limited.

Adult↗
PubMed1985

[Induction of human monocyte-mediated tumor cell killing by alpha or beta interferon].

Human blood monocytes, separated on a continuous percoll gradient, were not cytotoxic to allogeneic A375 melanoma cells. The monocyte monolayers were activated to become tumoricidal by incubation for 24 hr with interferon (IFN)-alpha or beta at concentrations of more than 1,000 IU/ml. Significant and reproducible activation of the monocytes was achieved by incubating them with 10,000 IU/ml of IFN-alpha or IFN-beta for 24 hr. Similarly, suspended, but not plated, monocytes were activated to a tumoricidal state by interaction with IFN-alpha or IFN-beta. Monocytes that had lost tumoricidal activity during culture, were reactivated by a second exposure to IFN-alpha. Fluorescence analysis showed that the monocyte-rich adherent monolayers were contaminated with up 2.0% of natural killer (NK) cells. Pretreatment of isolated monocyte preparations with anti-NK cell monoclonal antibody (Leu-11b) to deplete them of NK cell activity did not inhibit the monocyte-mediated cytotoxicity. These results indicate that human monocytes are rendered tumoricidal by direct interaction with IFN-alpha or IFN-beta, although more than 1,000 IU/ml of IFN-alpha or IFN-beta is required for maximal expression of monocyte activation.

Cell Line↗
PubMed1985

[Mechanism of cancer metastasis and its inhibition--a point of view from clinical aspects].

Metastasis is one of the most distinct but complicated biological phenomena in cancer. It is hard to decide the most important prospect which must be performed at the present as well as in future studies on cancer metastasis. However, the final goal of the studies on metastasis can be simply concluded as that metastasis should be prevented before dissemination. In this review, we discussed several points to do research in metastasis.

Animals↗
PubMed1985

[A case of remission in diffuse pleural mesothelioma induced by anticancer chemotherapy with cisplatin and adriamycin].

A 56-year-old man was admitted to our hospital with complaints of dyspnea and right pleural effusion. Malignant pleural mesothelioma was diagnosed, based on the high level of hyaluronic acid in the pleural fluid and manifestation of malignant cells by pleural needle biopsy. Anticancer chemotherapy with cisplatin and intrapleural injections of adriamycin against this mesothelioma was carried out because of the presence of stage III by Butchart's classification. Regression of the tumor, decrease of pleural fluid and decrease of LDH level in effusions were observed after this chemotherapy. Cisplatin was easily transported into the pleural fluid, and its concentration was maintained for a satisfactorily long period.

Antineoplastic Combined Chemotherapy Protocols↗