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Biomedical subjects

T Masuda

Publications and source records attributed to T Masuda.

At least 595 records · Page 33Linked to original sources

Effects of long-term intake of a fine-grained diet on the mouse masseter muscle.

Muscle fibers of the masseter muscle of mice which had been fed a fine-grained diet for various periods were studied histochemically and morphometrically. The diameters of both extrafusal and intrafusal muscle fibers decreased with time in mice fed a fine-grained diet, compared with those of control mice. In animals maintained on the special diet for 160 days after weaning at the 20th postnatal day, the effects of the diet on the diameter of muscle spindles were severe, and the diameter of each type of red and white fibers was significantly smaller than those of control animals. But a significant difference was not recognized in the diameter of intermediate fibers between control and treated mice. Unexpectedly, white fibers having a smaller diameter than red fibers were observed in diet-fed mice after the 180th postnatal day, although white fibers having such small diameter were not detectable in control animals. Succinic dehydrogenase activities were decreased in both extrafusal and intrafusal fibers of experimental animals. Moreover, muscle spindles with no annulospiral endings were increased in number in mice fed the diet for 130 and 160 days after weaning, although those spindles also increased in control animals. The diameters of outer capsules and primary endings were also significantly decreased in the animals kept on the diet for a long time. These effects of the fine-grained diet on the mouse masseter muscle became severer with time.

Adaptation, Physiological↗

Immunologic identification of lymphocyte subsets in experimental murine myocarditis with encephalomyocarditis virus. Different kinetics of lymphocyte subsets between the heart and the peripheral blood, and significance of Thy 1.2+ (pan T) and Lyt 1+, 23+ (immature T) subsets in the development of myocarditis.

To clarify the immune mechanism in myocarditis, immunofluorescence techniques with laser flow cytometry were used to examine serial changes in lymphocyte subsets in the heart, spleen, and peripheral blood of DBA/2 and BALB/c mice inoculated with encephalomyocarditis virus (Experiment I). B cells were identified by staining with fluorescein isothiocyanate-labelled rabbit anti-mouse immunoglobulin. T-cell subsets were identified with rat anti-Thy 1.2, and nonpolymorphic Lyt 1 and Lyt 2 monoclonal antibodies plus fluorescein isothiocyanate-labelled anti-mouse immunoglobulin. On days 7 and 14 postinfection, the percentage of Thy 1.2+ (pan T) cells in both strains had decreased in the peripheral blood; B cells showed no significant changes throughout the entire period. On the other hand, Thy 1.2+ (pan T) and Lyt 1+, 23+ (precursor and immature) T cells appeared to occupy the major portion of the myocardium on days 7 and 14 when congestive heart failure developed. To confirm this, serial immunohistologic studies (immunoperoxidase staining) of the hearts of DBA/2 and BALB/c mice with encephalomyocarditis virus-induced myocarditis were performed (Experiment II). In Experiment II, most of the stained cells in the hearts of both strains were Thy 1.2 positive and Lyt 1 and Lyt 2 positive on days 7 and 14. Thus, Experiments I and II demonstrated that lymphocytes at the site of inflammation in acute viral myocarditis carried antigenic markers that differed from those of peripheral lymphocytes and suggested that Thy 1.2+ (pan T) cells, especially the Lyt 1+, 23+ subset (immature T cells and T-cell subset precursors) were involved in the development of myocarditis in these animals.

Animals↗

Immunosuppressive activity of 15-deoxyspergualin and its effect on skin allografts in rats.

The immunosuppressive activity of spergualin analogues, 15-deoxyspergualin and N-30, is presented. These compounds suppressed antibody formation and establishment of delayed-type hypersensitivity to sheep red blood cells (SRBC) in mice. Among spergualin, 15-deoxyspergualin, and N-30, 15-deoxyspergualin was most effective in suppressing immune responses. It suppressed antibody formation against SRBC by spleen cell cultures in a dose-dependent fashion without reducing cell viability. The spergualins also suppressed the mixed lymphocyte culture reaction. Peritoneal exudate cells taken from mice given immunosuppressive doses of 15-deoxyspergualin were not reduced in their functions measured: Release of lysosomal enzymes and production of superoxide anions. 15-Deoxyspergualin and N-30 were markedly effective in prolonging skin graft in rats.

Animals↗

Antitumor cells found in tumor-bearing mice given ubenimex.

Antitumor effector cells in spleens of tumor-bearing mice given ubenimex were investigated. The administration of ubenimex, starting 7 days after the tumor inoculation, was effective in inhibiting growth of IMC carcinoma. Spleen cells taken from these mice showed a marked suppression of the tumor growth by the WINN assay. The antitumor activity of spleen cells was reduced by treatment to remove T cells or NK cells, whereas spleen cell preparations enriched for T cells showed the strongest antitumor activity. Moreover, NK activity against YAC-1 cells was found in the spleen. These results indicate that the administration of ubenimex to IMC carcinoma-bearing mice generates cytotoxic T cells and NK cells in the spleen. The antitumor effect of ubenimex was not observed in X-ray-irradiated and in anti-asialo GM1 serum-treated mice.

Adjuvants, Immunologic↗

Inhibitory mechanism of the proliferative responses of resting B cells: feedback regulation by a lymphokine (suppressive B-cell factor) produced by Fc receptor-stimulated B cells.

We investigated the effect of a lymphokine termed 'suppressive B-cell factor' (SBF), which is produced by FcR gamma (Fc receptor for IgG)-stimulated B cells or hybridoma TS4.44, and is known to suppress B-cell responses in vivo and in vitro by inhibiting their proliferation. Small B cells, fractionated by Percoll density gradient, from athymic nude mice (BALB/c) secreted SBF after binding EA (sheep erythrocytes sensitized with IgG mouse anti-sheep erythrocyte antibody), and the proliferation of small but not large B cells was preferentially suppressed by SBF in response to LPS in vitro. Proliferation of purified B cells from BALB/c nu/nu mice, induced by a synergistic interaction between F(ab')2 fragment of goat anti-mouse IgM antibody and B-cell stimulating factor (BSF1), was almost completely abrogated by the co-existence of SBF during the 72-hr culture period. However, the co-culture with SBF for the last 24 or 48 hr, as well as of B cells pretreated with SBF for 1 hr at 37 degrees, partially inhibited the growth response. These findings suggest that SBF operates on resting B cells and holds them in a resting state. This notion would be further supported by the fact that SBF inhibited G0-G1 transition. Taken together, we conclude that SBF acts on the early step of B-cell activation, thereby inhibiting B-cell growth. Arrest of resting B cells in the G0 phase and failure of an increase in functional receptors for BSF1 seem to be responsible for the suppression of B-cell responses.

Animals↗

Selective IgM deficiency in adults: phenotypically and functionally altered profiles of peripheral blood lymphocytes.

Peripheral blood lymphocytes from four patients with selective IgM deficiency were examined phenotypically and functionally. Although B cell subpopulations determined by surface immunoglobulins were within normal or nearly normal range, T8+ cells were significantly increased and T4/T8 ratios were inverted in three patients. IgM specific hyporesponsiveness in the PWM-driven immunoglobulin production system was observed in all four patients. Ia-like antigen positive T cells were increased in two patients; both had increased Leu2a+ Leu15+ suppressor-effector cells. In addition, Leu3a+ Leu8+ suppressor-inducer cells were increased in one of these two patients. Excessive (either IgM-specific or isotype non-specific) suppressor activity of T cells and IgM specific hyporesponsiveness of non-T cells were observed in these two patients in the recombination plaque assay. Although these results showed the complexity of the pathogenesis of this syndrome, they suggested that suppressor-associated T cells may play a role in some patients with selective IgM deficiency.

Adult↗

Inhibitory mechanism of the proliferative response of B lymphocytes: suppression of the proliferation induced by anti-mu antibody and BSF1 by immune complexes.

We studied the effect of immune complexes (IC) on the responses of polyclonally activated murine B cells. For this, normal resting B cells were stimulated with the F(ab')2 fraction of goat anti-mouse mu-chain antibody and B-cell stimulating factor 1 (BSF1) after preculturing them with IC. Next, the relative membrane potential changes and the subsequent proliferative response were analysed. IC, particularly in antibody excess, inhibited both membrane depolarization and while those in antigen excess did poorly. Neither antigen nor antibody alone was effective. Inhibition was mediated via binding of IC to FcR gamma on B cells in a dose-dependent manner. Kinetic experiments showed that at least 6 hr was necessary for inducing the suppression of B-cell responses after binding of IC. We conclude that IC bound to FcR gamma on B cells regulates B-cell responses by acting on the initial step of activation.

Animals↗

[Complete response of unresectable gastric cancer (Borrmann's type III) treated with combination chemotherapy of UFT and mitomycin--a case report].

A 69-year-old male visited our hospital in December, 1983, complaining of dysphasia. X-ray and endoscopic examination of the stomach revealed Borrmann's type 3 of the cardia. A biopsy specimen revealed typical features of adenocarcinoma. Because the tumor could not be resected, chemotherapy was started in February, 1984 with a combination of UFT (600 mg/day) and mitomycin (6 mg/week). After five courses of the combination chemotherapy, UFT therapy was continued. Follow-up endoscopy in August, 1985, showed a discolored area of the cardia. A biopsy specimen revealed no evidence of carcinoma. UFT-M therapy is a useful chemotherapy for gastric cancer.

Adenocarcinoma↗

[Inhibition of the growth of a murine transplantable tumor, colon 26, by the prostaglandin synthetase inhibitor, indomethacin].

Cancer cells and macrophages produce large amounts of prostaglandin (PG) E2, which suppress cellular immune r action in tumor-bearing individuals. These findings raised a possibility that PG synthetase inhibitor can restore the immune reactivity against tumors. The anti-tumor activity of indomethacin, a potent PG synthetase inhibitor, by oral administration of 0.002% water solution as drinking water from the day 0 or 7 days after tumor transplantation was investigated in BALB/c or CDF1 (BALB/c X DBA/2) mice implanted subcutaneously with colon carcinoma 26 (10(6) cells) as a series of model studies for cancer treatment. The treatment with indomethacin substantially 1) inhibited the tumor growth, 2) prolonged the survival time, 3) caused a regression and disappearance of tumor with some cured mice and 4) reduced the levels of PGE2 and ornithine decarboxylase activity, a first rate limiting enzyme of polyamine synthesis in tumor tissue. Those anti-tumor activities were 5) reduced by a concomitant administration of PGE2 and 6) increased by a combined administration of an immunopotentiating agent, Picibanil (OK-432). The results indicate that indomethacin inhibited the synthesis of PGE2 in the tumor tissue, which suppress the non-specific cellular immune reaction against tumor cells, resulting in the regression and disappearance of tumor. PG synthetase inhibitor may be effective also against human cancer.

Administration, Oral↗

[Prevention of peritoneal carcinomatosis recurrence with a prostaglandin synthesis inhibitor, indomethacin].

Carcinomas produce large amounts of prostaglandin (PG) E2, which play an important role in suppression of non-specific cellular immune reaction in tumor-bearing individuals. PG synthesis inhibitor can restore the immune activity against tumors. The anti-tumor activity of indomethacin was investigated in CDF1 mice (BALB/c X DBA/2) implanted intraperitoneally with mouse colon adenocarcinoma 26 (5 X 10(5) or 2 X 10(5) cells) in a model study to prevent peritoneal recurrence after surgery for gastrointestinal cancers. Oral administration of indomethacin (0.002% water solution as drinking water) depressed and inhibited the disseminated tumor growth in the abdominal cavity, and prolonged the survival time, resulting in 30-50% cures of mice. The treatment combined with a small intraperitoneal dose of Picibanil (OK-432) (0.5 mg/kg twice weekly), which activates macrophages in the abdominal cavity, cured 90% of mice. An intraperitoneal dose of 16,16-dimethyl-PGE2 (5 micrograms/mouse, daily) reduced the anti-tumor activity of indomethacin. The results suggest that indomethacin treatment relieved the endogenous(tumor cell- and macrophage-produced) PGE2-mediated immunosuppression. It is postulated that PG-synthesis inhibitor in combination with chemotherapeutic agents, immunotherapeutic agents and low dose radiation, may provide a good therapeutic tool to prevent the development of peritoneal carcinomatosis, particularly in the cases having a small number of residual cancer cells or micrometastases in the abdominal cavity after surgery.

Adenocarcinoma↗

Alcuronium pretreatment attenuates succinylcholine-induced increases in plasma catecholamine concentrations in humans.

The effect of alcuronium given before succinylcholine (SCh) on plasma catecholamine concentrations, systolic blood pressure and heart rate was studied in patients anesthetized with enflurane. Twenty-one patients were divided into three groups; six control patients without SCh, eight SCh (1 mg/kg) patients, and seven pretreated patients given alcuronium, 0.04 mg/kg, 5 min before SCh, 1 mg/kg. In the SCh group, mean plasma norepinephrine concentrations, systolic blood pressure, and heart rate significantly increased with onset of fasciculations, whereas in the pretreated patients these variables did not change significantly and no fasciculation was observed. These results indicate that alcuronium pretreatment significantly attenuates the SCh-induced increases in plasma norepinephrine concentrations, systolic blood pressure and heart rate.

Adult↗

[A case of breast carcinoma with lung metastasis].

A 37-year-old female, who had undergone a left standard mastectomy in May, 1983 for breast cancer, was treated with Tamoxifen and FT-207 postoperatively. The patient had no further evidence of disease until two and one-half years later, when a routine chest film showed a single, half-rounded density 6.5 cm in diameter in the hilus of her left lung. Bestrabucil, the benzoate of an estradiol-chlorambucil conjugate, was administered p.o. at a daily dose of 200 mg for four weeks. Thereafter, the tumor greatly decreased in size to 3.0 cm in diameter. When a left upper lobectomy was performed, the tumor was found to be necrotic tissue. Microscopically, a small cancer nest similar to the primary breast carcinoma was observed in the center of the necrosis. The necrotic tissue was surrounded with cellular infiltrate, markedly consisting of histiocytes.

Adenocarcinoma↗

[Clinical study of a synthetic calcitonin derivative (elcatonin) in patients with metastatic bone tumors].

Forty-three cases of metastatic bone tumor were treated with Elcatonin. The agent was injected intramuscularly to each patient at a dose of 40 units twice daily. Twelve patients (28%) experienced pain relief within 4 days after treatment and after 4 weeks, twenty-eight patients (65%) had palliation of pain. In patients with hypercalcemia (4 cases), a decrease of serum Ca was observed one week after administration of Elcatonin. Improved bone scintigram was observed in 37.5% of cases, and radiographic improvement in 20% of cases. These data indicate that Elcatonin is effective for achieving pain relief and in improving the state of invaded bones when administered in combination with conventional treatment modalities for patients with metastatic bone tumors.

Adult↗

Monoclonal antibody (H107) inhibiting IgE binding to Fc epsilon R(+) human lymphocytes.

A hybridoma-producing monoclonal antibody blocking the binding of human IgE to lymphocytes Fc receptor (Fc epsilon R) was established by the fusion of murine myeloma cells. P3X63.653.Ag8, with BALB/c spleen cells immunized with Fc epsilon R(+) human B lymphoblastoid cell line cells, RPMI1788. A clone of the hybridoma (H107) produced a monoclonal IgG2b antibody that inhibited the rosette formation of Fc epsilon R(+) human B lymphoblastoid cell line cells (RPMI1788, RPMI8866, CESS, Dakiki, and IM9) with fixed ox red blood cells (ORBC) conjugated with human IgE (IgE-ORBC). In contrast, the rosette formation with IgG-conjugated ORBC (IgG-ORBC) on Fc gamma R(+), Fc epsilon R(-) Daudi cells were not affected by the H107 antibodies. A close association of Fc epsilon R and the antigenic determinant recognized by H107 antibody was suggested by the following results. First, the bindings of 125I-labeled IgE (125I-IgE) or 125I-labeled H107 IgG2b antibody (125I-H107) to RPMI8866 cells were inhibited by cold human IgE and H107 IgG2b but not by other classes of human Ig (IgA and IgG), MPC11 IgG2b, or unrelated monoclonal antibodies. Second, H107 antibody reacted with Fc epsilon R(+) B cell lines but not with Fc epsilon R(-) B cell lines as determined by an indirect immunofluorescence. Third, Fc epsilon R(+) cells were depleted by the incubation in the dish coated with H107 antibody or IgE but not in the dish coated with unrelated antibodies. Finally, there was a correlation between the increase of Fc epsilon R(+) cells and that of H107(+) cells in the peripheral blood lymphocytes of the patients with atopic dermatitis. The surface antigens on Fc epsilon R(+) RPMI8866 cells recognized by H107 antibodies had the molecular size of 45,000 as determined by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis.

Antibodies, Monoclonal↗