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Biomedical subjects

S Kishimoto

Publications and source records attributed to S Kishimoto.

At least 325 records · Page 18Linked to original sources

Effects of estrogen and vanadate on the proliferation of newly established transformed mouse Leydig cell line in vitro.

A permanent cell line (B-1-A-2) derived from an estrogen-responsive mouse Leydig cell tumor (T 124958-R) was established in culture. Although this cell line showed estrogen-induced enhancement of cell proliferation in vitro, a moderately high concentration (10(-8) M) of estradiol was required to stimulate maximum growth. A whole cell binding assay revealed that the B-1-A-2 cells contained estrogen receptors with relatively low affinity for estradiol (Kd, 10(-9)-10(-8) M). This estrogen receptor was found to have a mol wt of 65,000. In addition, incubation of the cells with [32P]orthophosphate and subsequent purification revealed that the estrogen receptor is phosphorylated. This finding prompted us to study the effect of phosphatase inhibitors on cell proliferation. The inclusion of vanadate (25 microM) in the culture medium resulted in a significant increase in estrogen sensitivity, showing a maximal growth stimulatory effect of estradiol at concentrations of 10(-10)-10(-9) M. Simultaneously, the conversion of the low affinity to the high affinity receptor (Kd, 10(-10)-10(-9) M) was induced by treatment of cells with vanadate. These data suggest that estrogen directly stimulates the growth of B-1-A-2 cells in culture, and that the sensitivity to estrogen can be altered by modulating the estrogen receptor possibly via a phosphorylation-dephosphorylation mechanism.

Animals↗

Diagnosis of familial amyloidotic polyneuropathy: isolation of variant prealbumin.

A novel, small-scale method was developed for detecting carriers of a prealbumin variant associated with type 1 familial amyloidotic polyneuropathy (FAP). Prealbumin isolated from plasma by a two-step preliminary chromatographic procedure was further separated into two peaks by reverse-phase high-performance liquid chromatography. The normal and variant prealbumins were identified by secondary ion mass spectrometry. The procedure is relatively simple, reliable, and applicable to the definitive diagnosis of FAP in affected patients and also as a preclinical test for the offspring of patients with FAP.

Adolescent↗

A case of von Recklinghausen's disease associated with pheochromocytoma and papillary carcinoma of the thyroid gland.

A 58-year-old woman was admitted to our hospital complaining of headache, dizziness and intermittent elevation of blood pressure. Multiple café-au-lait spots and neurofibromas had appeared on the back and the limbs since the age of 30 years. At the age of 54 years she underwent total thyroidectomy because of papillary carcinoma of the thyroid gland. On admission, the levels of plasma norepinephrine and epinephrine, urinary norepinephrine and normetanephrine were all within the normal range. However, urinary excretion of metanephrine was markedly increased to 1.49 +/- 0.45 (Mean +/- SD) mg/day and that of epinephrine was also slightly increased. The computed tomographic scans of the abdomen and the scintigraphy with 131I-metaiodobenzylguanidine revealed a tumor mass in the region of the right adrenal gland. The tumor was histologically confirmed to be pheochromocytoma at the operation. In her family history, her mother and one of her two sisters had von Recklinghausen's disease and another sister suffered from follicular carcinoma of the thyroid gland. As far as we know, this paper is the first report of a patient with von Recklinghausen's disease associated with both pheochromocytoma and non-medullary carcinoma of the thyroid gland, and her family.

Carcinoma, Papillary↗

Demonstration of specific dopamine receptors on human pituitary adenomas.

Dopamine receptors on human pituitary adenoma membranes were characterized using [3H] spiperone as the radioligand. The specific [3H]spiperone binding sites on prolactin (PRL)-secreting adenoma membranes were recognized as a dopamine receptor, based upon the data showing high affinity binding, saturability, specificity, temperature dependence, and reversibility. All of 14 PRL-secreting adenomas had high affinity dopamine receptors, with a dissociation constant (Kd) of 0.85 +/- 0.11 nmol/l (mean +/- SEM) and a maximal binding capacity (Bmax) of 428 +/- 48.6 fmol/mg protein. Among 14 growth hormone (GH)-secreting adenomas examined, 8 (57%) had dopamine receptors with a Kd of 1.90 +/- 0.47 nmol/l and a Bmax of 131 +/- 36.9 fmol/mg protein. Furthermore, 15 of 24 (58%) nonsecreting pituitary adenomas also had dopamine receptors with a Kd of 1.86 +/- 0.37 nmol/l and a Bmax of 162 +/- 26.0 fmol/mg protein. These results indicate that some GH-secreting adenomas as well as some nonsecreting pituitary adenomas contain dopamine receptors. But their affinity and number of binding sites are significantly lower (P less than 0.05) and fewer (P less than 0.001) respectively, than those in PRL-secreting adenomas.

Adenoma↗

[Radiotherapy and tumor immunity--analysis using monoclonal antibodies].

In order to better understand the immunologic effects of irradiation, blood levels of lymphocyte subsets were sequentially monitored in 37 patients before and during irradiation treatment for lung cancer. Tumor infiltrating lymphocytes induced by radiotherapy were analysed by the avidin-biotin-horseradish peroxidase method. 49 cases of head and neck cancer were examined. In some cases, remarkable infiltration of lymphocytes was observed surrounding cancer cells during radiotherapy. This infiltration was mainly composed of anti-Leu-3a + 3b positive lymphocytes, and HLA-DR positive cancer cells were remarkably observed.

Antibodies, Monoclonal↗

Significance of suppressor macrophages for immunosurveillance of tumor-bearing mice.

The in vivo significance of suppressor macrophages for antitumor immunity was investigated in a syngeneic tumor system. The presence of suppressor macrophages in the spleens of X5563 C3H/HeN tumor-bearing mice (TBM) was directly shown in vitro. Thus the addition of splenic macrophages of TBM suppressed the in vitro secondary induction of both tumor-specific cytotoxic T-cells and effector cells of the delayed-type hypersensitivity reaction. Splenic macrophages of TBM exerted suppression on tumor-specific T-cell-mediated cytotoxicity in the effector phase as well. Prostaglandin production was found to be one of the major mechanisms involved in macrophage-induced suppression. In vivo treatment of TBM with carrageenan and/or indomethacin retarded tumor growth and in parallel augmented cell-mediated cytotoxicity against X5563 cells, probably by affecting suppressor macrophages in vivo. The suppressive effect of splenic macrophages from TBM was clearly demonstrated in a tumor-neutralization test indicating that suppressor macrophages were able to exert their function in vivo as well as in vitro. All these results suggested that suppressor macrophages had in vivo significance for the suppression of the immunosurveillance of the hosts.

Animals↗

Synergistic antitumor effects of BCG and monoclonal antibodies capable of inducing antibody-dependent cell-mediated cytotoxicity.

Three monoclonal antibodies (MAbs) of different immunoglobulin subclasses against MH134 murine ascitic hepatoma cells, detecting the same antigenic determinant of tumor-associated antigen of the tumor cells, were tested for their ability to produce a synergistic antitumor effect with Mycobacterium bovis BCG in C3H/HeN mice. 12A2 (IgG2a) induced both antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against the tumor cells. C3H/HeN mice were inoculated ip with MH134 tumor cells (day 0), and received an ip injection of BCG (day 1) and/or 12A2 (day 5). The combined therapy with BCG and 12A2 brought about a significant prolongation of the survival period, whereas either BCG or the MAb alone exhibited poor therapeutic effectiveness. 11G2 (IgG1), inducing ADCC but not CDC against MH134 tumor cells, was shown to exhibit antitumor effects as potent as those of 12A2, when used in combination with BCG. However, 7C2 (IgM), capable of inducing CDC but not ADCC to the tumor cells, produced no apparent synergistic effect with BCG. ADCC of BCG-induced peritoneal cells was mediated by the adherent cell population of the cells and abolished by the addition of carrageenan, suggesting that the effector cells of the cytotoxicity were macrophages. Moreover, carrageenan abolished the combined antitumor effect of BCG and these MAbs in the serological Winn assay. These results suggest that activated macrophages play a major role in the synergistic antitumor effect of BCG and MAbs capable of inducing ADCC against MH134 tumor.

Animals↗

[Squamous cell carcinoma and adenosquamous cell carcinoma of the thyroid gland].

Two cases of a squamous cell carcinoma and an adenosquamous cell carcinoma of the thyroid gland are presented. Both cases have survived without recurrence for 18 months and 31 months respectively, although these cases have an unfavorable prognosis. A review of the Japanese literature reveals that these two tumors differ significantly in their clinical features. In cases involving a squamous cell carcinoma the ratio of female to male patients is lower, the duration of the illness before treatment is shorter, and the prognosis is poorer than those with an adenosquamous cell carcinoma. These features suggest that the carcinomas have a different histogenesis.

Adenocarcinoma↗

Effects of isosorbide on perilymphatic pressure and oxygenation.

Using a servocontrolled micropipet pressure measuring system, the effect of intravenous and oral administration of isosorbide, a hyperosmolar agent that is an anhydrate of sorbitol, was examined in 11 fasting cats. Following intravenous administration of 2 g/kg of the agent, perilymphatic pressure has shown, on the average, a significant reduction of 136% of the initial value (3.6 +/- 0.3 mm Hg). A strong rebound phenomenon, however, with a 61% rise to the initial value, was noted, and this did not come down in 3 hours. On the contrary, no rebound phenomenon was noted after oral administration, which caused a significant 60% drop in perilymphatic pressure for more than 90 minutes. Using polarographic technique, perilymphatic oxygen tension was measured and showed a maximal increase of 145% to the initial value. The time it took to reach the maximal PO2 tension was equal to the time it took to come down to the minimal perilymphatic pressure. This is a strong indication that isosorbide improves perfusion and increases blood flow of the inner ear vessels.

Administration, Oral↗

Therapeutic effects of sofalcone on experimental gastritis.

A study was made on the therapeutic effects of sofalcone (SU-88), an antiulcer agent, on erosive and atrophic gastritis induced experimentally by 6-month administration of 5 mmol/l of sodium taurocholate (TCA) in rats. A standard meal including sofalcone of 0.25% and 1.0% shortened the total length of erosions, normalized the mucosal thickness, and reduced collagenous fibers in the gastric mucosa in one month. The doses administered were 116.3 mg and 486.1 mg/kg/week for one month. Sofalcone, thus, had a good therapeutic effect on experimental erosive and atrophic gastritis in rats.

Animals↗

Mechanisms of age-related decline in antigen-specific T cell proliferative response: IL-2 receptor expression and recombinant IL-2 induced proliferative response of purified Tac-positive T cells.

Proliferative response of T cells from aged persons was significantly reduced to a specific antigen tuberculin-active peptide (TAP) determined by [3H]TdR uptake and FCM in comparison to that from the young. Cytokinetic analysis for the proliferative response to TAP showed that, in the aged, the clonal size or the number of the first generation responding cells to TAP was not significantly reduced but the ability to repeat replication was more profoundly affected. Neither the delayed entry into the cell replication nor prolongation of the cell cycle time could explain these results. Similar results have been reported on the proliferative response of T cells to mitogen: PHA (Phytohemagglutinin). Expression of Tac-antigen on T cells determined by anti-Tac antibody binding with FACS after stimulation with either TAP or PHA was found to be reduced significantly in the aged. Both the numbers of high and low affinity IL-2 receptors determined by radiolabelled IL-2 binding assay were also reduced in the aged, but the degree of reduction in number of high affinity ones was more pronounced than that in low affinity ones. Tac-positive T cells were isolated with the use of anti-Tac rosette methods and stimulated with recombinant IL-2 (r-IL-2). Their proliferative response was significantly lower in the aged than that in the young at any concentration of r-IL-2 examined. The number of the first generation responding cells to r-IL-2 in purified Tac-positive T cells from the aged was 82% of that from the young whereas the proliferative response by aged T cells was 39% of that by young ones when the cells were allowed to repeat replication for 3 days. The mechanisms of these multifactorial defects in proliferation of T cells from aged persons were discussed.

Adult↗