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Biomedical subjects

D Mizuno

Publications and source records attributed to D Mizuno.

At least 109 records · Page 6Linked to original sources
PubMed1983

Combination therapy of murine tumors with lentinan, bacterial lipopolysaccharide and a Streptococcus preparation, OK432.

Combination therapy by intralesional injection of OK432 followed by intraperitoneal administration of lentinan and bacterial lipopolysaccharide caused almost complete regression of solid-type tumor MH134. All three components were needed for maximal antitumor activity. Mice in which MH134-tumor had regressed due to this combination therapy showed an augmented antitumor delayed hypersensitivity reaction (measured by the footpad test) and resistance to rechallenge with MH134, but they had no cytolytic antibodies in their serum detectable by the complement cytotoxicity test. The possible importance of local inflammation induced by OK432 in this combination therapy is discussed.

Animals↗
PubMed1983

Antitumor activity of polysaccharide TC-13 extracted from rare actinomycetes.

The antitumor activities of mycelia and a hot-water extract of mycelia of rare actinomycetes were examined by three different antitumor assays in ddY mice with Ehrlich solid tumor. A new antitumor polysaccharide, TC-13, was prepared from the hot-water extract of Microellobosporia grisea by precipitation with cetylpyridinium chlorideborate complex and gel filtration. TC-13 was mainly composed of glucose and mannose with peptideglycan. Its molecular weight was determined to be 2-30 X 10(4) by gel filtration. Comparative studies suggested that the antitumor activity of TC-13 was equal to, or stronger than those of other antitumor agents (e.g., lentinan, PS-K, OK432 and yeast mannan). Screening methods for antitumor activity of actinomycetes were also discussed.

Actinomycetales↗
PubMed1983

Immunotherapy of murine tumor with syngeneic antitumor serum plus BCG.

Murine tumor suppression was observed on combination therapy with antitumor serum and BCG at a low dose. However, no tumor suppression was observed with a relatively high dose of 400 micrograms BCG. Macrophages from mice given a high dose of BCG showed low cytolytic activity but high phagocytic activity in vitro. In BCG- sensitized mice, BCG was effective on early ascitic tumors. Moreover, combination therapy with antitumor serum and BCG was effective on tumors at an advanced stage. These results suggest that in combination, antiserum and BCG have synergistic therapeutic effects on tumors of BCG-sensitized and nonsensitized hosts.

Animals↗
PubMed1983

Marine animal lectin-dependent tumor recognition by macrophages.

Several lectins from marine animals, such as Balanus roseus hemagglutinin, B. balanoides hemagglutinin, Tetraclita squamosa japonica hemagglutinin and Aplysia kurodai agglutinin, were tested for induction of tumor lysis mediated by macrophages. Among them, B. roseus and B. balanoides lectins agglutinated several murine tumor cells and induced binding of macrophages to tumor cells. Binding of these cells was inhibited by galacturonic acid, suggesting that carbohydrate moieties on the cell membrane of the two types of cells are recognized by these lectins. These lectins did not induce tumor lysis in co-operation with various macrophages, but after inactivation of tumor cells with glutaraldehyde, they induced extensive lysis of target cells in the presence of macrophages. B. roseus lectin was also effective in vivo. These results suggest that tumor cells can be recognized via carbohydrate moieties on the cell membrane as well as tumor-associated antigen and that some animal lectins participate in macrophage-mediated cytolysis and tumor rejection.

Agglutination↗
PubMed1982

An Fc-receptor activity of plasma membranes from guinea-pig peritoneal polymorphonuclear leucocytes.

Plasma membranes prepared from guinea-pig peritoneal polymorphonuclear leucocytes showed an immune-complex-binding activity that corresponded well with the activity in intact cells. The characteristics of this activity were reversible binding, dependence on the Fc portion of antigen-complexed IgG (immunoglobulin G), competition with aggregated IgG and independence from energy metabolism. These results support the conclusion that the binding activity found in the isolated plasma membranes is an Fc-receptor activity of guinea-pig peritoneal polymorphonuclear leucocytes. The activity showed Kd = 6.7 x 10(-8) M-IgG and maximum binding of 17 pmol of IgG/mg of membrane protein when measured with an immune complex of alpha-amylase and homologous guinea-pig anti-(alpha-amylase) IgG. Inhibition of the Fc-receptor activity by a series of various salts indicated the contribution of the hydrophobic interaction to the binding. Inhibitory effects of salts or metal-chelating reagents on the Fc-receptor activity were also observed on superoxide generation by these cells induced by the immune complex, suggesting a role of the Fc receptor as the immune-complex-binding site responsible for the initiation of superoxide generation.

Animals↗
PubMed1982

Preparation of polymorphonuclear leucocyte-plasma membranes which show Fc receptor activity.

A plasma membrane-rich fraction was prepared from guinea pig peritoneal polymorphonuclear leucocytes (PMNs) by a nitrogen cavitation method. Fc receptor activity was measured in the fraction. The activity showed a Kd of 5 X 10(-7) M IgG and a maximum binding of 33 pmol IgG/mg protein when measured with an immune complex made with bovine serum albumin and rabbit anti-(bovine serum albumin) immunoglobulin G. Properties of the Fc receptor in the plasma membrane fraction were similar to that in intact PMNs. It is proposed that the Fc receptor activity and 5'-nucleotidase activity are markers for plasma membranes of these cells.

Animals↗
PubMed1982

Comparative studies on immunological properties of antitumor polysaccharide TC-13.

The biological and immunological characteristics of TC-13, an antitumor protein-bound polysaccharide, were studied. TC-13 had no direct cytocidal effect on Ehrlich carcinoma, but it induced antitumor resistance in mice whose tumors were regressed by TC-13. TC-13 changed the electrophoretic pattern of serum proteins of mice after its ip administration, causing a slow increase of the LB component and a rapid increase of the X component. TC-13 augmented the delayed-type hypersensitivity reaction to tumor homogenate, anti-SRBC antibody formation and the cytocidal activity of macrophages in an antibody-dependent system, but it had little or no effect on blast formation of spleen lymphocytes or carbon clearance. These results and comparative studies with other immunomodulators suggest that TC-13 is a unique polysaccharide having properties intermediate between those of lentinan, a simple-structured homologous polysaccharide from basidiomycetes, and lipopolysaccharide, a cell-surface component from bacteria.

Animals↗
PubMed1982

Enhanced susceptibility of glutaraldehyde-treated tumor cells to antibody-dependent macrophage-mediated cytolysis.

The effect of treatment of target tumor cells with glutaraldehyde (GA) on antibody-dependent macrophage-mediated cytolysis was investigated in a C3H/He mouse-MM46 syngeneic tumor system. GA-treated tumor cells were more susceptible to antibody-dependent macrophage-mediated cytolysis. Lysis of GA-treated cells was observed with less antibody and fewer macrophages than that of untreated cells. However, GA-treated cells had the same amount of antigen sites and the same activity of antibody-dependent attachment to macrophages as do fresh tumor cells. Thus, this enhancement of lysis did not occur at the antibody-binding step or the early step of contact between macrophages and tumor cells but at the subsequent step, perhaps at the tumor lysis step. GA-treated tumor cells could not synthesize DNA or RNA, but cells attenuated with mitomycin C or actinomycin D were not susceptible to antibody-dependent macrophage-mediated cytolysis. These results suggest that the cytostatic effect of GA does not involve change in susceptibility of target cells to lysis, but some impairment of the cell membrane. GA-treated tumor cells could not grow in vivo and could induce antitumor immunity.

Aldehydes↗
PubMed1982

Antitumor effect of polysaccharide TC-13 on allogeneic and syngeneic tumors in mice.

The antitumor activity of TC-13, a protein-bound polysaccharide extracted from a rare actinomycetes was tested on allogeneic and syngeneic tumors in mice. In the allogeneic Ehrlich carcinoma system, TC-13 showed antitumor activity over a broad optimal dose range, when administered by various routes such as ip, iv, sc, it (intratumorally) or po, even when given before tumor inoculation. TC-13 showed synergistic antitumor effects in combination with other immunomodulators, e.g., lipopolysaccharide, lentinan and picibanil. It showed antitumor activity against syngeneic tumors, MM46 mammary carcinoma and MCS-8 and Meth A fibrosarcoma.

Animals↗
PubMed1982

Induction of macrophage-mediated tumor lysis by an animal lectin, Sarcophaga peregrina agglutinin.

Several animal lectins, such as Sarcophaga peregrina agglutinin, Limulus polyhemus agglutinin, Helix pomatia agglutinin and Helix aspersa agglutinin, were tested for induction of tumor lysis mediated by macrophages. Among them, only S. peregrina agglutinin purified from the hemolymph of S. peregrina larvae lysed tumor cells in co-operation with macrophages from the peritoneal cavity of mice. S. peregrina agglutinin alone did not kill target tumor cells. Macrophages in the presence of this lectin could kill other syngeneic tumor cells. This lectin-dependent cytolysis by macrophages was inhibited by galactose, a sugar which is specifically recognized by S. peregrina agglutinin. These findings suggest that the animal lectin S. peregrina agglutinin is a ligand in macrophage-mediated cytolysis, inducing binding of effector macrophages to target cells which in turn triggers off lysis of the target cells.

Agglutinins↗
PubMed1982

Combination therapy of murine tumors with lentinan plus lipopolysaccharide plus cyclophosphamide.

A combination of lentinan and bacterial lipopolysaccharide (LPS), previously reported to have strong antitumor activity against some tumors, was only slightly effective on solid-type MH134 hepatoma and colon 38 adenocarcinoma and was not effective on ascitic L1210 in CDF1 mice. On the other hand, additional combination therapy with cyclophosphamide (CY), that is, lentinan plus LPS plus CY, strongly inhibited the growth of solid-type MH134 and colon 38 adenocarcinoma even when administered from day 12 after tumor inoculation. The antitumor delayed hypersensitivity reaction against MH134 hepatoma, measured by means of the footpad test, was augmented by this combination. The possible role of CY is discussed in relation to the importance of inhibition of immune suppressive mechanisms in this combination therapy.

Adenocarcinoma↗
PubMed1982

Changes of antitumor immunity of hosts with murine mammary tumors regressed by lentinan: potentiation of antitumor delayed hypersensitivity reaction.

From 2 weeks after sc inoculation of MM46 mammary carcinoma cells into C3H/He mice, lentinan caused tumor regression, irrespective of its administration schedule (i.e., various doses and times of treatment, before and after tumor inoculation). The humoral and cellular immune responses of tumor-bearing mice with or without lentinan treatment were studied kinetically. From 2 weeks after tumor inoculation, antitumor antibodies (detected by macrophage-mediated or complement-dependent cytotoxicity assay) and LB (a serum protein) increased in tumor-bearing mice but the delayed-type hypersensitivity reaction against tumor (T-DHR) decreased. Lentinan restored and potentiated the T-DHR. The conditions under which lentinan is effective and the antitumor reactions responsible for tumor regression are discussed on the basis of these results.

Adjuvants, Immunologic↗
PubMed1981

A possible mechanism of induction of insect lectin.

Studies were made using antibody against a lectin induced in the hemolymph of Sarcophaga peregrina larvae on injury. The results suggested that the alpha subunit (Mr = 32,000) of the lectin is normally present in the hemolymph. On injury of the body wall, part of the alpha subunit seems to be converted to the beta subunit (Mr = 30,000), probably by partial proteolysis with a protease activated in response to the injury. As a result, an active lectin with the structure alpha 4 beta 2 is formed.

Animals↗
PubMed1981

Stimulation of messenger ribonucleic acid synthesis in isolated nuclei by a protein that stimulates RNA polymerase II.

A factor stimulating RNA polymerase II purified from Ehrlich ascites tumor cells was found to stimulate alpha-amanitin-sensitive RNA synthesis in nuclei isolated from spleen cells of anemic mice, though less than it stimulated purified RNA polymerase II. The fidelity of the resulting RNA synthesis was monitored by measuring the stimulation of globin mRNA synthesis. Globin mRNA was measured quantitatively by DNA-RNA hybridization by using plasmid DNA containing globin DNA sequences. Results showed that the synthesis of globin mRNA was enhanced in isolated nuclei in the presence of this factor coinciding with an increase of overall alpha-amanitin-sensitive RNA synthesis. Thus, it was concluded that an externally added factor did not stimulate random transcription but meaningful RNA synthesis in isolated nuclei.

Anemia↗
PubMed1981

Differences in the rates and extents of fusion between lysosomes and phagocytic vesicles containing different particles.

The rates and extents of fusion between lysosomes and phagocytic vesicles containing different kinds of particles were investigated kinetically in guinea pig polymorphonuclear leukocytes (PMNs). Particles were prepared by emulsifying paraffin oil with bovine serum albumin (POE-BSA), with hemoglobin (POE-Hb), and with ovalbumin (POE-OA). PMNs phagocytosed these particle in the order, POE-BSA greater than POE-Hb greater than POE-OA. As for fusion with lysosomes, the recoveries of lysosomal enzymes in the phagolysosome fraction during phagocytosis did not vary greatly, but the ratios of lysosomal enzymes to paraffin oil in the phagolysosome fractions, designated as "the fusion index," showed considerable differences, varying in reverse order to that of phagocytosis. Further studies were carried out on fusion between lysosomes and phagocytic vesicles as distinct from phagocytosis. PMNs were allowed to phagocytize particles at 37 degrees C for 5 min, then were washed free from non-ingested particles and reincubated without phagocytizable particles. The fusion index showed a slow but continuous increase in cells with POE-BSA, and a rapid but temporary increase in those with POE-Hb and POE-OA at 37 degrees C. These results suggest that different particles caused differences in the rate and extent not ony of phagocytosis but also of fusion with lysosomes.

Acid Phosphatase↗
PubMed1981

Purification and characterization of RNase-inhibitor complex from rat reticulocytes.

During purification of the RNase-inhibitor complex from rat reticulocytes, two forms of the complex were separated by DEAE-Sephadex chromatography. One complex was purified 10,000-fold from the cell lysate, and the other 1,000-fold. Both complexes were shown to be composed of 1 mol of RNase and 1 mol of inhibitor. Reconstitution experiments revealed that the multiplicity of the complex was primarily due to differences in the RNase. The RNases derived from the two complexes differed in their sensitivities to metal ions and hemin.

Animals↗