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T Suda

Publications and source records attributed to T Suda.

At least 847 records · Page 47Linked to original sources
PubMed1983

Cooperative effect of 1 alpha,25-dihydroxyvitamin D3 and dexamethasone in inducing differentiation of mouse myeloid leukemia cells.

Murine myeloid leukemia cells (MI) are induced to differentiate into macrophages by the metabolically active form of vitamin D3,1 alpha,25-dihydroxyvitamin D3[1 alpha,25(OH)2D3] (E. Abe et al., (1981) Proc. Natl. Acad. Sci. USA 78, 4990-4994). At 0.12-120 nM, 1 alpha,25(OH)2D3 suppressed cell growth in a dose-dependent manner and markedly induced phagocytic activity, lysozyme activity, and C3-receptor formation. The potency of 1 alpha,25(OH)2D3, at 0.12-120 nM, in inducing differentiation was nearly equivalent to that of 10-10,000 nM of dexamethasone, one of the most potent stimulators of Ml cells. Simultaneous treatment with low physiological plasma concentrations of 1 alpha,25(OH)2D3 (0.12 nM) and dexamethasone (10 nM) induced differentiation of Ml cells equivalent to the responses obtained only by using much higher concentrations of the respective steroids when used separately. In addition, two variant clones of Ml cells resistant to either 1 alpha,25(OH)2D3 or dexamethasone were isolated. One was resistant to 120 nM of 1 alpha,25(OH)2D3 but sensitive to 10-1000 nM of dexamethasone. The other was resistant to 1000 nM of dexamethasone but sensitive to 12 nM of 1 alpha,25(OH)2D3. This suggests that the mechanism of action of 1 alpha,25(OH)2D3 in inducing differentiation of Ml cells is different at least in part from that of dexamethasone, and that combination therapy by both steroids may be useful in reducing leukemogenicity of Ml cells in vivo.

Animals↗
PubMed1983

1 alpha,25-Dihydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3 prolong survival time of mice inoculated with myeloid leukemia cells.

Syngeneic SL mice inoculated with murine myeloid leukemia cells (M1) all died of leukemia within 30 days. Treatment three times a week with 12.5-50 pmol per mouse of either 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], the active form of vitamin D3, or its synthetic analog, 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3], considerably prolonged the survival time of mice inoculated with M1 cells. 1 alpha(OH)D3 was more effective than 1 alpha,25(OH)2D3 in increasing the survival time of the mice. 1 alpha(OH)D3 also increased the survival time of nude mice inoculated with M1 cells. The 1 alpha(OH)[3H]D3 administered intraperitoneally to tumor-bearing mice was converted very rapidly to 1 alpha,25(OH)2-[3H]D3. The chronic administration of 25 pmol of 1 alpha(OH)D3 to tumor-bearing mice for 30 days caused no appreciable hypercalcemia. These results indicate clearly that 1 alpha,25(OH)2D3 is effective not only in inducing differentiation of M1 cells in vitro, as previously reported [Abe, E., Miyaura, C., Sakagami, H., Takeda, M., Konno, K., Yamazaki, T., Yoshiki, S. & Suda, T. (1981) Proc. Natl. Acad. Sci. USA 78, 4990-4994], but also in prolonging the survival time of mice inoculated with M1 cells.

Animals↗
PubMed1983

1 alpha,25-dihydroxyvitamin D3 promotes fusion of mouse alveolar macrophages both by a direct mechanism and by a spleen cell-mediated indirect mechanism.

Extensive fusion was induced in mouse alveolar macrophages by treatment with conditioned media obtained from spleen cell cultures treated with 15 micrograms of phytohemagglutinin or concanavalin A per ml or with 12 nM 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3]. The fusion rate was 80-90% on day 3. In addition, 1 alpha,25(OH)2D3 added directly to alveolar macrophages induced fusion of about 35% of the cells on day 3, whereas direct addition of phytohemagglutinin and concanavalin A did not enhance fusion at all. When conditioned media from spleen cell or T cell cultures treated with 12 nM 1 alpha,25(OH)2D3 were applied to a Sephadex G-100 column, a fusion factor (Mr 37,000-70,000) could be separated from 1 alpha,25(OH)2D3. 1 alpha,25(OH)2D3 induced fusion at 0.012-120 nM in a dose-dependent manner both by direct action and by spleen cell-mediated indirect action, but the fusion rate was always much greater in the latter than in the former at each concentration of the vitamin. Of the vitamin D3 derivatives tested, 1 alpha,25(OH)2D3 was the most potent, followed successively by 1 alpha,24R,25-trihydroxyvitamin D3, 1 alpha-hydroxyvitamin D3, 25-hydroxyvitamin D3, and 24R,25-dihydroxyvitamin D3. These results clearly indicate that 1 alpha,25(OH)2D3 induces fusion of mouse alveolar macrophages by both a direct and an indirect mechanism, the latter mediated by spleen cells, probably by T cells.

Animals↗
PubMed1983

Single-cell origin of mouse hemopoietic colonies expressing multiple lineages in variable combinations.

By using a micromanipulator, single cells from blast cell colonies were individually transferred to 35-mm culture dishes for secondary colony formation. When individual colonies appeared to be mature, they were examined for cellular composition by May-Grunwald-Giemsa staining and were replated for determination of unexpressed hemopoietic potentials. We describe here a total of 50 mixed hemopoietic colonies. Seven types of colonies consisting of cells in two different lineages were seen--i.e., neutrophil-macrophage, neutrophil-eosinophil, macrophage-eosinophil, macrophage-mast cell, macrophage-megakaryocyte, macrophage-erythrocyte, and erythrocyte-megakaryocyte. Six types of colonies revealed three cell lineages--i.e., neutrophil-macrophage-eosinophil, neutrophil-macrophage-mast cell, neutrophil-macrophage-erythrocyte, macrophage-mast cell-erythrocyte, neutrophil-macrophage-megakaryocyte, and neutrophil-erythrocyte-megakaryocyte lineages. In addition, multilineage colonies expressing terminal differentiation in varying combinations of more than three lineages were present. Replating studies confirmed that the progenitors for many of these colonies are terminally committed to differentiation only in the lineages disclosed by staining. This study, thus, provides a proof for the single-cell origin of mouse hemopoietic colonies expressing various combinations of cell lineages. It also supports the hypothesis that the differentiation of multipotential hemopoietic progenitors is through progressive and stochastic restriction in cell lineages.

Animals↗
PubMed1983

Protective effect of alpha-tocopherol on the morphological and rheological changes of rat red cells.

The effect of alpha-tocopherol on the rheological properties of rat red cells was studied. The suspension viscosity of red cells increased, as the alpha-tocopherol content in red cells decreased. The red cells gradually transformed to echinocytes in isotonic solution dependent on the alpha-tocopherol content. The unique correlations among the viscosity, the transformation, and alpha-tocopherol content were observed. It was shown that the increased suspension viscosity of alpha-tocopherol-deficient cells could have arisen from the difficulty of echinocytes to undergo high shear deformation. The possible mechanism is discussed.

Animals↗
PubMed1983

Effects of bilateral adrenalectomy on immunoreactive corticotropin-releasing factor in the rat median eminence and intermediate-posterior pituitary.

Immunoreactive ACTH (I-ACTH) concentrations in the anterior pituitary (AP), intermediate-posterior pituitary (IP) and plasma, and immunoreactive corticotropin-releasing factor (I-CRF) concentrations in the median eminence (ME) and IP, were determined in adrenalectomized rats from 3 h till 14 days after surgery. Plasma I-ACTH concentrations showed the typical triphasic response over time. AP I-ACTH concentrations decreased immediately after surgery, then increased to high concentrations 3 days after surgery. I-ACTH concentrations in IP did not change through these periods. I-CRF concentrations in ME and IP decreased immediately after surgery, then gradually increased to high concentrations (ME) or to control levels (IP) 14 days after surgery. These results raise the possibility that the I-CRF in IP is of hypothalamic origin.

Adrenalectomy↗
PubMed1983

Regulation of terminal differentiation of cultured mouse epidermal cells by 1 alpha,25-dihydroxyvitamin D3.

Terminal differentiation of mouse epidermal cells in primary culture was found to be regulated by 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3), the hormonal form of vitamin D3 produced by sequential hydroxylations in the liver and kidney. Epidermal differentiation was stimulated dose dependently by 1 alpha,25(OH)2D3 at concentrations of 0.12 nM or more. In the presence of the vitamin, stratified foci increased in number and size and contiguous foci coalesced. Basal cells in the treated cultures decreased sharply and underwent differentiation into squamous and enucleated cells which sloughed off into the medium during cultivation. The size and density of the cells became larger and lighter during the course of differentiation. 1 alpha,25(OH)2D3 markedly stimulated formation of a cornified envelope, a structure with chemically stable cross-links formed beneath the plasma membrane. Of several derivatives of vitamin D3 examined, 1 alpha,25(OH)2D3 was the most potent in inducing epidermal differentiation. Stimulation of epidermal differentiation was also observed in low calcium medium. DNA synthesis was inhibited dose dependently by 1 alpha,25(OH)2D3. A specific receptor for 1 alpha,25(OH)2D3 was found in the cytosol fraction of the epidermal cells. Scatchard plot analysis revealed that the receptor has an apparent dissociation constant (Kd value) of 54 pM and maximum binding value (Nmax) of 43 fmol/mg protein. The specificity of the receptor was demonstrated by analog competition in the following order: 1 alpha,25(OH)2D3 much greater than 25-hydroxyvitamin D3 greater than 1 alpha-hydroxyvitamin D3 greater than 24R,25-dihydroxyvitamin D3.

Animals↗
PubMed1983

Functional defect of variant clones of a human myeloid leukemia cell line (HL-60) resistant to 1 alpha,25-dihydroxyvitamin D3.

Two variant clones of a human myeloid leukemia cell line (HL-60) resistant to the active metabolite of vitamin D3, 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], were isolated from a 1 alpha,25(OH)2D3-sensitive parent clone, and the mechanism of the resistance was examined. When the parent clone was incubated with 120 nM 1 alpha,25(OH)2D3, cell growth was suppressed to half of the control and about half of the cells exhibited phagocytic activity and C3 rosette formation on day 3. The variant clones, however, were resistant to 120 nM 1 alpha,25(OH)2D3. One of the variant clones was also insensitive to other potential inducers such as 12-O-tetradecanoyl-phorbol-13-acetate, actinomycin D, and dimethyl sulfoxide. When the variant clones were incubated with 1 alpha,25(OH)2[3H]D3, they took up much less radioactivity than the parent clone into the whole cells, and into the cytosol protein-bound and chromatin-bound fractions. The variant clones were found to possess reduced amounts of the cytosol receptor protein to which 1 alpha,25(OH)2D3 was specifically bound; but the hormone-receptor complex could be transferred to the chromatin acceptor sites similarly both in the wild type clone and its variant clones, indicating that one of the major defects in the 1 alpha,25(OH)2D3-resistant clones is the reduced amounts of the specific cytosol receptor. These results support the concept that 1 alpha,25(OH)2D3 induces differentiation of human myeloid leukemia cells by a receptor-mediated mechanism.

Calcitriol↗
PubMed1983

Pituitary adenomas that caused Cushing's disease or Nelson's syndrome are not responsive to ovine corticotropin-releasing factor in vitro.

The response of pituitary adenomas obtained surgically from patients with Cushing's disease of Nelson's syndrome to synthetic ovine corticotropin-releasing factor (CRF), vasopressins, somatostatin-28, dexamethasone, 3-isobutylmethylxanthine or high [K+] was examined in vitro by measuring the amount of pro-opiomelanocortin (POMC)-derived peptides secreted into the culture medium. CRF did not stimulate the secretion of adrenocorticotropin-, beta-endorphin-, or gamma 3-melanotropin-like peptides from the pituitary adenomas at concentrations ranging from 1 x 10(-13) M to 1 x 10(-7) M whereas vasopressins, 3-isobutyrl-methylxanthine and high [K+] increased, while somatostatin-28 and dexamethasone suppressed, the secretion of these POMC-derived peptides. These findings suggest that either the pituitary ACTH-producing tumors have lost their receptors to CRF or their post-receptor mechanism to CRF is not functional.

Adenoma↗
PubMed1983

Effects of cyproheptadine, reserpine, and synthetic corticotropin-releasing factor on pituitary glands from patients with Cushing's disease.

Direct effects of cyproheptadine, reserpine, synthetic ovine corticotropin-releasing factor (CRF), dexamethasone, and lysine-8-vasopressin (LVP) on the secretion of immunoreactive ACTH and beta-endorphin from the adenoma and the nonadenomatous tissue of patients with Cushing's disease were examined using a superfusion system. Cyproheptadine and reserpine (10(-9)-10(-7) M of each) suppressed immunoreactive ACTH and beta-endorphin secretion from both tissues. CRF (10(10)-10(7) M) stimulated the secretion of both peptides from the nonadenomatous tissue, but only a high dose of CRF could stimulate the secretion of these peptides from some adenomas. Such CRF-induced secretion was partially suppressed by dexamethasone. LVP (10(-9)-10(-7) M) stimulated peptide secretion from both types of tissue. These results suggest direct inhibitory effects of cyproheptadine and reserpine on the secretion of these peptides from the pituitary of patients with Cushing's disease, a different stimulatory mechanism of LVP from that of CRF in these tissues, and low sensitivity of the adenoma to CRF.

Adenoma↗
PubMed1983

Presence of immunoreactive corticotropin-releasing factor in human cerebrospinal fluid.

Immunoreactive corticotropin-releasing factor (I-CRF) was measured by radioimmunoassay and immunoaffinity chromatography in human hypothalamus and cerebrospinal fluid (CSF). Dilution curves of I-CRF in the hypothalamus and CSF were parallel to that of synthetic ovine CRF standard. I-CRF content in the hypothalamus was 643 and 281 fmol eq, respectively. I-CRF concentration in CSF was 7.4 +/- 1.1 fmol eq/ml. Sephadex G-75 column chromatography showed the main peak eluted at the position of synthetic CRF.

Chromatography, Affinity↗
PubMed1983

Corticotropin-releasing factor test in normal subjects and patients with hypothalamic-pituitary-adrenal disorders.

Corticotropin-releasing factor (CRF) tests were performed in normal subjects and patients with hypothalamic-pituitary-adrenal disorders. In normal subjects, after iv administration of 500 micrograms synthetic ovine CRF, plasma ACTH rose significantly to approximately 3.6 times the basal level at 30-60 min and cortisol reached a peak of 2.3 times the basal level at 60-90 min, whereas aldosterone peaked at 1.6 times the basal level at 60 min. Injection of 100 micrograms CRF in normal subjects also caused a significant increase in plasma ACTH and cortisol levels but only a slight increase in aldosterone. However, the total hormone released and their peak levels were lower than those elicited by the 500-microgram dosage. In patients with Cushing's disease, although the basal and peak levels of plasma ACTH and cortisol induced by administration of CRF were variable, the ratios of increase for the two hormones elicited by CRF were lower than those in normal subjects, especially for cortisol. In patients with Cushing's syndrome due to an adrenal adenoma, basal levels of ACTH were markedly suppressed and plasma ACTH and cortisol did not rise after CRF. In patients with isolated ACTH deficiency or Sheehan's syndrome the basal level of plasma ACTH was less than 5 pg/ml and no change in plasma ACTH occurred after injection of CRF. In patients with Nelson's syndrome or Addison's disease the basal levels of ACTH were extremely elevated but infusion of CRF increased plasma ACTH to even higher levels.

Addison Disease↗
PubMed1983

Immunoreactive corticotropin-releasing factor concentrations in cerebrospinal fluid from patients with hypothalamic-pituitary-adrenal disorders.

The concentrations of immunoreactive corticotropin-releasing factor (I-CRF) in human cerebrospinal fluid (CSF) were measured utilizing immunoaffinity chromatography and RIA in patients with no endocrine disease, patients with Cushing's disease, Nelson's syndrome, Sheehan's syndrome, Addison's disease and steroid treated patients. On high performance liquid chromatography, the elution profile and retention time of I-CRF in CSF were not identical with ovine CRF. I-CRF concentrations in CSF from patients with Cushing's disease and Sheehan's syndrome were lower than those from normal subjects, however those from patients with Nelson's syndrome and Addison's disease were within the normal range. I-CRF concentrations in CSF from patients with Cushing's disease returned to normal levels 2-9 months after pituitary adenomectomy. These results suggest that CSF I-CRF concentrations are reduced by increased plasma corticosteroid levels.

Addison Disease↗
PubMed1983

Ectopic ACTH-, beta-LPH- and beta-endorphin-producing metastatic carcinoma of the lung from the tonsil.

A rare case of metastatic lung cancer from the tonsil associated with ectopic ACTH, beta-LPH and beta-endorphin production was presented. A year ater the tonsillectomy and lymphadenectomy, the patient had metastatic lung cancer. Three years later he died. Brown pigmentation remained evident for a month before his death. Both ACTH and cortisol levels were high in the plasma. ACTH, beta-LPH and beta-endorphin were found in the tissue extracts (squamous cell carcinoma).

ACTH Syndrome, Ectopic↗
PubMed1983

In vitro differentiation of leukemic progenitor cells in various types of acute nonlymphocytic leukemia.

The effects of colony-stimulating factors on differentiation of leukemic progenitor cells were investigated in various types of acute nonlymphocytic leukemia. Two different sources of colony-stimulating factors were used in this study: human placental conditioned medium; and phytohemagglutin-stimulated leukocyte-conditioned medium. At the end of culture, colony types were determined by dual esterase staining in permanent preparations. The majority of the colonies formed in acute myeloblastic and acute promyelocytic leukemias were neutrophilic even when stimulated by phytohemagglutinin-stimulated leukocyte-conditioned medium, which contains a potent stimulator of macrophage colony growth from normal marrow cells. On the other hand, both neutrophilic and monocytic colonies were formed in acute myelomonocytic leukemia (AMMoL). The proportions of these two types of colonies were variable, depending on the nature of added colony-stimulating factor and its concentration. These findings suggest that the leukemic progenitors in acute myeloblastic and acute promyelocytic leukemias have a tendency to differentiate mainly into a neutrophilic lineage in vitro and that the leukemic progenitors in AMMoL differentiate into both neutrophilic and monocytic lineages in vitro, in two cases of esterase-negative AMMoL, both neutrophilic and monocytic colonies were detected as in the other well-defined cases of AMMoL. This study seems to be of value in understanding the nature of leukemic progenitor cells and also shows that morphological analysis of leukemic colonies may be helpful in the classification of acute nonlymphocytic leukemia.

Cell Differentiation↗
PubMed1983

Regulatory mechanism of granulopoiesis in the bone marrow of CSF-producing tumor-bearing nude mice.

The regulatory mechanism of differentiation of granulocyte and macrophage precursor cells (G/M CFU-C) in bone marrow and spleen obtained from nude mice bearing colony-stimulating factor (CSF) producing tumor (G-mice), which developed marked granulocytosis, was studied. In these mice, granulopoiesis is enhanced in the spleen, but suppressed in bone marrow. Coculture of G-mouse bone marrow cells with splenic cells of control nude mice (C-mice) and of G-mice resulted in 68% and 62%, respectively, more colonies than expected, while coculture of C-mouse bone marrow cells with these two sources of cell fractions resulted in only 2% and 11% more colonies. In the double-layer agar culture system, bone marrow and splenic cells of C- and G-mice produced a maximal number of colonies containing adequate amounts of human urinary CSF in the upper layer when C-mouse bone marrow cells were added to the lower layer, while these four sources of cells produced a moderate or minimal number of colonies when splenic cells of C- and G-mice or G-mouse bone marrow cells were added to the lower layer. Morphological examination of colonies formed in the upper layer revealed that addition of C-mouse bone marrow cells or irradiated G-mouse bone marrow cells to the lower layer resulted in a massive increment in the number of colonies with pure granulocytes and granulocyte and macrophage mixed (G + G/M) colonies formed by G-mouse bone marrow cells in the upper layer. However, the addition of irradiated C-mouse bone marrow cells or G-mouse bone marrow cells before irradiation to the lower layer did not change G + G/M colony formation by G-mouse bone marrow cells in the upper layer. We could reproduce these findings with conditioned media obtained from 3-day liquid cultures of these cell fractions. This suggests that a diffusible factor may be necessary for inhibition of G + G/M colony formation in G-mouse bone marrow cells. The fine mechanism of such inhibition remains to be clarified.

Animals↗