Search PubMedSearch

Biomedical subjects

E Tsubura

Publications and source records attributed to E Tsubura.

At least 19 recordsLinked to original sources

Initial appearance of an ill-defined shadow on a chest roentgenogram in a patient with aortitis syndrome.

A 20-years-old woman with fever and an abnormal shadow on a chest roentgenogram was admitted to our hospital. High grade fever continued even after gradual disappearance of the ill-defined shadow on the right upper lobe (S3) with minor fissure deviation upward, while neck pain and bruit gradually developed. She was diagnosed as aortitis syndrome from a digital subtraction angiography. The initial appearance of an ill-defined shadow on a chest roentgenogram, considered as pulmonary infarction, is rare in the aortitis syndrome and this kind of onset is interesting in relation to the pathogenesis and diagnosis of this syndrome.

Angiography, Digital Subtraction

[Clinical effect of miconazole gel against upper digestive tract mycosis].

A total of 43 patients, comprising 41 patients with oral candidiasis and 2 with esophageal candidiasis, were treated with miconazole (MCZ) gel to assess its efficacy and safety in treating upper digestive tract mycosis. The efficacy of the drug was evaluable in 33 of them, consisting of 32 patients with oral candidiasis and 1 with esophageal candidiasis. The clinical efficacy rate of the drug against oral candidiasis was 87.5% (28/32 patients), and the clinical response was good in the 1 evaluable patient with esophageal candidiasis. The safety of the drug was assessed in 40 patients. In 3 (7.5%) of them, nausea occurred as an adverse event, but was not particularly serious in any of them. No abnormal laboratory test values caused by the drug were observed. The results suggested that MCZ gel would be a very useful drug in treating oral and esophageal candidiasis.

Adolescent

Effects of experimental hyper- and hypothyroidism on natural defense activities against Lewis lung carcinoma and its spontaneous pulmonary metastases in C57BL/6 mice.

The effects of expermentally induced hyper- and hypothyroidism on the growth and development of spontaneous pulmonary metastases of Lewis lung carcinoma (3LL) cells were studied in a murine system. Progression of 3LL tumors growing in mice was associated with significant reduction in the serum levels of T3 and T4. Subcutaneous (s. c.) injections (3 times/week) of T3 resulted in a hyperthyroid state with elevated T3 and reduced T4, whereas treatment with T4 induced a hyperthyroid state with elevated T3 and T4 levels. On the other hand, treatment with methimazole induced hypothyroidism with reduced T3 and T4 levels. Under these experimental conditions, treatment with T3 significantly inhibited spontaneous pulmonary metastases, and prolonged survivals of the mice. Methimazole suppressed primary and metastatic tumor growth and prolonged survival. In contrast, treatment with T4 enhanced primary tumor growth and development of pulmonary metastases of 3LL cells. Alveolar macrophages showed enhanced cytotoxicity against 3LL tumor cells after injections of thyroid hormones (T3 and T4) for 4 weeks. The NK activities of spleen cells of mice treated with T4 or methimazole were much lower than those of control mice, and were not affected by treatment with T3. These results imply that changes in thyroid functions may have important influence on natural host defenses against primary and metastatic lung cancer in humans.

Animals

[Muramyl dipeptide derivative and its clinical application].

Muramyl dipeptide (MDP) and its synthetic derivatives which comes from the major constituent of bacterial cell wall has various biological activities as host defence mechanisms. One of the synthetic MDP derivatives, MDP-Lys (L 18), muroctasin has potent biological activities with less adverse reactions among various MDP derivatives. Muroctasin has proved to be safe to use clinically as the results of phase I clinical study. We attempted to evaluate its clinical usefulness and safety from the view point of restorative activity in leukopenia that was induced by cancer chemotherapy in patients with malignancies. It is concluded that muroctasin is effective as well as useful on the restorative activities against leukopenia in lung cancer patients after cancer chemotherapy, with the optimal daily dosage of 200 micrograms for six times by subcutaneous injections through phase II and phase III clinical cooperative studies in Japan. Supposed mode of action of muroctasin for granulocytosis may be the results of CSF production due to stimulation of macrophage by muroctasin. This first clinical success of restoration of leukopenia in patients with cancer receiving cancer chemotherapy by MDP derivative, muroctasin, might be not only advantageous for cancer chemotherapy and/or radiation therapy but also for preventing infections occurring in compromised host due to neutropenia in cancer patients by means of cytotoxic cancer chemotherapy or irradication.

Acetylmuramyl-Alanyl-Isoglutamine

[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

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

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

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

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