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Biomedical subjects

Y Honma

Publications and source records attributed to Y Honma.

At least 379 records · Page 21Linked to original sources

Differentiation of mouse myeloid leukemia cells is inhibited by a factor from non-differentiating leukemia cells.

Mouse myeloid leukemia cells (MI) were induced to differentiate by a factor(s) (D-factor) in ascitic fluid. An inhibitory activity (I-activity) for the induction of differentiation was present in conditioned medium and lysate of MI cells resistant to the D-factor. The I-activity was non-dialyzable, heat-labile and protease-sensitive. Most of the activity was recovered in the fraction precipitated with 30-50% saturated ammonium sulfate. The fraction inhibited induction of phagocytic activity, migrating activity and morphological changes in MI cells, which are typical properties of differentiated MI cells. Low levels of I-activity were detected in conditioned medium or lysate of MI cells sensitive to the D-factor. The resistant MI cells were sensitized to the D-factor by treatment with a low concentration (5-10 ng/ml) of actinomycin D. The I-activity in conditioned medium of actinomycin D-treated resistant cells decreased with development of sensitivity to the D-factor. These results suggest that production of the I-activity in the resistant cells is closely associated with resistance of the MI cells to the D-factor.

Animals↗

Experimental demonstration of the cell types in the adenohypophysis of the gobiid fish, Rhinogobius brunneus.

The hypophysis of the common freshwater goby, Rhinogobius brunneus, accompanying gonadal maturation, was studied light microscopically to determine the cell types by the aid of the administration of antithyroidal and antiadrenocortical drugs. It is peculiar in that the hypophysis is entirely buried in the hypothalamus, and that the entire adenohypophysis is covered with a thin layer of the neurohypophysis. Two types of cells, azocarminophil prolactin cells and PbH-positive adrenocorticotrophs, are discernible in the rostral pars distalis. The proximal pars distalis consists of three types of cells: weakly AF positive thyrotrophs, strongly AF positive gonadotrophs and orangenophil somatotrophs. In spite of the application of several stainings, only one cell type, the PbH-positive cell, is demonstrated in the pars intermedia.

Adrenocorticotropic Hormone↗

Histological observations on some of the endocrine glands in the ironfish, with special regard to the hypophysis.

Endocrine glands of the ironfish were studied light microscopically to elucidate the relationship between the races of the genus Carassius. The rostral pars distalis of the adenohypophysis consists mainly of acidophils corresponding to prolactin cells and lead-hematoxylin positive cells corresponding to corticotrophs (ACTH cells). The prolactin cells are obviously arranged in the form of follicles. The proximal pars distalis contains orangenophils (STH cells) and two types of basophils (TSH and GTH cells). In the pars intermedia, three types of cells are identified: periodic acid Schiff positive cells, lead-hematoxylin stainable cells and orangenophils containing PAS positive coarse granules. In addition, small agranular cells are seldom demonstrated in the entire adenohypophysis. A considerable amount of aldehyde fuchsin positive neurosecretory material is laden in the cells of the nucleus preopticus and in the pars nervosa. The nucleus lateralis tuberis is composed of three portions: pars anterior, pars posterior, and pars lateralis. The thyroid follicles found in the pharyngeal region and head kidney show a mild state of activity. The interrenal cells intermingled with the chromaffin cells have a considerable amount of eosinophil cytoplasm. Judging from the gonadal condition, the breeding season of the ironfish may extend to the end of July.

Animals↗

Relationship between leukemogenicity and in vivo inducibility of normal differentiation in mouse myeloid leukemia cells.

Leukemogenicity was studied in sensitive mouse myeloid leukemia cells that could be induced to undergo cell differentiation in vitro into mature granulocytes and macrophages by incubation with the inducer (certain proteins or glucocorticoids) and in resistant myeloid leukemia cells that could not be induced to differentiate into mature cells. Three sensitive and five resistant clones were tested. The resistant cells were much more leukemogenic than the sensitive cells, and the survival time of syngeneic mice inoculated with the sensitive cells. In a diffusion chamber in a syngeneic, inbred SL mouse without any additional manipulation or injection of inducer, the resistant cells remained undifferentiated, but the sensitive cells were induced to differentiate into mature granulocytes and macrophages and their proliferation rate decreased. These results suggested that the greater leukemogenicity of resistant cells is associated with some defect in inducibility of cell differentiation.

Animals↗

Inhibition of RNA and protein syntheses makes non-differentiating mouse myeloid leukemia cells sensitive to a factor(s) stimulating differentiation.

Treatment with ascitic fluid from animals bearing various tumors, can induce mouse myeloid leukemia line cells, M1, to differentiate in vitro into macrophages and granulocytes. Cells were isolated that were resistant to the ascitic fluid factor(s) stimulating differentiation (D-factor). The resistant cells became sensitive to the D-factor and differentiated after treatment with various inhibitors of RNA synthesis (actinomycin D, nogalamycin, chromomycin A3 or cordycepin) or protein synthesis (puromycin or cycloheximide). The cells could not be induced to differentiate by treatment with the inhibitors alone. The effective doses of the inhibitors of protein synthesis were toxic to the cells. Among these inhibitors actinomycin D (5 ng/ml) was the most effective for sensitizing the resistant cells. Inhibitors of DNA synthesis did not sensitize the resistant cells. Added actinomcyin D was mainly recovered in the nuclear fraction of the cells. The sensitizing effect of actinomycin D on the cells was roughly parallel to the extent of its inhibition of RNA synthesis in the cells. The effective concentration of actinomycin D (5 ng/ml) mainly inhibited it also inhibited alpha-amanitin-resistant RNA synthesis to some extent. These results suggest that alpha-amanitin-sensitive RNA synthesis may be involved in sensitization of the resistant cells to the D-factor.

Animals↗

Glucocorticoid binding and mechanism of resistance in some clones of mouse myeloid leukemic cells resistant to induction of differentiation by dexamethasone.

Several clones of dexamethasone-resistant cells, which could not differentiate even in a high concentration of dexamethasone, were isolated from glucocorticoid-sensitive myeloid leukemic cells. Some of them were shown to be deficient in steroid binding to specific cytoplasmic receptors, while the others contained glucocorticoid-specific cytoplasmic receptors that might be the same as those in sensitive cells. One of the resistant clones was found to be almost completely deficient in nuclear acceptor sites for cytoplasmic steroid-receptor complexes. The remaining clones were also characterized by significantly reduced amounts of nuclear-bound glucocorticoid. These results suggest that resistibility to glucocorticoids in the resistant clones of myeloid leukemic cells is due mainly to a defect in some steps of intracellular transfer of the steroid. Dexamethasone-sensitive cells, which could differentiate in the presence of dexamethasone, could be also induced to differentiate by protein factor(s) in ascitic fluid. Although all the resistant cells showed a low response to ascitic fluid, some of them showed 10-fold enhancement of phagocytic activity which is a typical character of differentiated cells. These results suggest that response to steroids is not directly correlated with that to protein inducer(s).

Animals↗

Azabicycloalkanes as analgetics. 3. Structure-activity relationships of 1-phenyl-6-azabicyclo[3.2.1]octanes and absolute stereochemistry of (+)-1-(3-hydroxyphenyl)-6-methyl-6-azabicyclo[3.2.1]octane and its 7-endo-methyl derivative.

A series of 53 1-phenyl-6-azabicyclo[3.2.1]octanes (1) has been tested for their analgetic and narcotic antagonist activities. Structure-activity relationships were investigated by varying the structural parameters. The most interesting compound in this series, the 1-(3-hydroxphenyl)-6,7-dimethyl derivative 8, shows the profile of a well-balanced antagonist-analgesic agent with a very mild physical dependence capacity. The absolute stereochemistry of its active enantiomer [(+)8] was established by the x-ray study and the chemical transformation to the phenylmorphan [(+)-II]. (+)-8 was stereochemically correlated also with the active enantiomer of the 7-demethyl derivatives [(+)-7] by chemical transformation and CD measurement. Certain structural and stereochemical correlations between these compounds (7 and 8) and other known antagonist-analgetics are discussed.

Analgesics↗

Scanning electron microscopy of the third ventricular wall in the lamprey, Lampetra japonica.

The third ventricular wall and its adjacent region of the arctic lamphrey, Lampetra japonica, were studied by scanning electron microscopy to elucidate their surface fine structures. The specimens were caught in the mouth of the river during their anadromous migration. The ventricular wall is covered entirely with the cilia of ependymal cells, with the exception of the ventral side of the lateral wall, the floor of the recessus infundibuli and a portion of the recessus posteriosus. In the ependymal layer covering the ventral side of the lateral wall, numerous protrusions of neurons are found equipped with microvilli and cilia. These neurons seem to correspond to the liquor-contacting neurons. Ependymal cells identified as tanycytes occur in the posterior portion of the floor of the recessus infundibuli. The apex of the tanycyte is provided with numerous microvilli and a bundle of cilia, while its basal projection extends towards the outer layer of neurohypophysis to make contact with the capillary wall. A small spherule considered to be a secretory substance is observed near the root of the ciliary bundle. tthe recessus posteriosus consists of a layer of ependymal cells and neurons with an apical projection into the ventricular cavity. Possible intraventricular macrophage (Kolmer cell) is found in the lamprey.

Animals↗

Differentiation of a resistant clone of mouse myeloid leukemia cells with dimethyl sulfoxide and ascitic fluid.

Mouse myeloid leukemia line cells, M1, could be induced to differentiate in vitro into macrophages and granulocytes with ascitic fluid of animals bearing various tumors. M1 cells could not be induced to differentiate with dimethyl sulfoxide alone. During the culture of M1 cells, spontaneously appearing cells resistant to factors stimulating differentiation (D-factor) in ascitic fluid were isolated. These resistant cells were more refractile to the toxic action of dimethyl sulfoxide than sensitive cells and grew in culture medium with 1% dimethyl sulfoxide. Although the resistant cells were not induced to differentiate with dimethyl sulfoxide alone, they were sensitized with the aid of dimethyl sulfoxide to undergo differentiation with the D-factor in ascitic fluid.

Animals↗

Glucorticoid-induced differentiation of cultured mouse myeloid leukemia cells.

Mouse myeloid leukemia cells were induced by some corticoid hormones to migrate in agar, phagocytize, and change into forms which were morphologically similar to macrophages and granulocytes. Inducing ability of corticoids was correlated with glucocorticoid activity, not mineralocorticoid activity. Other steroids were ineffective to induce differentiation of myeloid leukemia cells. Glucocorticoid-resistant cells, which could not differentiate even in a high concentrations of dexamethasone, were selected from steroid-sensitive cells by stepwise increase in concentrations of dexamethasone in culture medium.

Animals↗

Structure requirements and affinity of steroids to bind with receptor for induction of differentiation of cultured mouse myeloid leukemia cells.

Glucorticoid hormones induced differentiation of mouse myeloid leukemia cells. From comparison of the structure of steroids with their ability to induce phagocytic and locomotive activities, typical characters of mature macrophages and granulocytes, the simplest steroid with inducing ability was concluded to be a steroid with the structure of progesterone and one hydroxyl group at 11beta- or 21-position. The maximum induction ability seemed to require the structure of progesterone and three hydroxyl groups (at 11beta-, 17alpha-, and 21-positions). A single, 30-min pulse treatment with glucocorticoid was sufficient to induce differentiation of leukemia cells. Glucocorticoid receptors were detected in mouse myeloid leukemia cells. The binding affinity of various steroids for the cytoplasmic receptors was closely correlated with the activities of these compounds to induce differentiation of leukemia cells, suggesting that these receptors may be involved in hormonal induction of differentiation of various cells. This suggests that the binding reaction is important for differentiation of myeloid leukemia cells.

Animals↗