Biomedical subjects

H Sakagami

Publications and source records attributed to H Sakagami.

At least 271 records · Page 15Linked to original sources

PubMedDate not supplied

Induction of cytotoxic factor in mice by lignified materials combined with OK-432 (Picibanil).

Intravenous administration of pine cone lignin-related substance (Fr. VI) significantly stimulated OK-432-elicited cytotoxic factor (CF) production in ICR mouse serum. The level of CF elicited after OK-432 administration peaked after 2 h and declined to basal level within 6 h. The CF productibility depended greatly on both dose and the interval between the administration of the Fr. VI and OK-432. Most natural and synthetic lignins, their degradation products, and polysaccharides, including pine cone hemicellulose fractions, had much weaker CF-inducing (priming) activity. When Fr. VI was treated with NaCl02 to decompose the lignin portion, the priming activity was significantly reduced. The data suggest that the potent priming activity of Fr. VI might de a result of some conjugation between the lignin portion and other components including polysaccharides.

Animals↗

PubMedDate not supplied

Stimulation of interferon-gamma-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction.

PSK, a protein-bound polysaccharide extracted from the mycelia of Coriolus versicolor (Fr.) Quel, stimulated tumor necrosis factor-induced cytotoxicity against mouse L-929 fibroblast. PSK also stimulated interferon-gamma-induced differentiation of human myelogenous leukemic U-937 and THP-1 cells. The differentiated cells had higher proportions of cells that expressed NBT-reducing activity and alpha-naphthyl acetate esterase activity. Among four PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD) had the most potent stimulating activity. This is the first report regarding direct PSK modulation of cytokine action.

Animals↗

PubMedDate not supplied

Dependence of cytokine-induced human myelogenous leukemic cell differentiation on the type of serum in the medium.

Human myelogenous leukemic cell lines (ML-1, U-937, THP-1) were induced to differentiate by treatment with various cytokines such as tumor necrosis factor, interferon-gamma and interleukin-6. However, the extent of cell maturation depended upon the types and concentrations of sera included in the culture medium. The stimulating activity of human sera on the cytokine-induced differentiation significantly exceeded that of various lots of calf serum, horse serum, fetal calf serum and fetal bovine serum, and its stimulating effects were reproducibly observed irrespective of age and sex of normal volunteers. On Sephadex G-200 gel filtration chromatography, the stimulatory substance(s) present in human sera were separated from the inhibitory substance(s) eluted near the void volume.

Blood Proteins↗

PubMedDate not supplied

Antimicrobial spectrum of lignin-related pine cone extracts of Pinus parviflora Sieb. et Zucc.

Pine cones of Pinus parviflora Sieb., et Zucc, were extracted successively with 5% NaHCO3, 3% NH4OH, 1% NaOH and 4% NaOH, and the extracts were tested for ability to induce antimicrobial activity in mice infected with Staphylococcal aureus. Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans, or Salmonella enteritidis. These alkaline extracts were potent against the first 5 of these strains of microorganisms, and the activity was recovered mostly from their acid-precipitates at pH 5. After further fractionation on a Sephadex LH-60 column, the highest molecular weight fraction was most potent. Chemical structures in these bioactive fractions were assumed to be lignin-related structures, based on spectral data from UV, NMR and IR spectroscopy.

Anti-Bacterial Agents↗

PubMedDate not supplied

Stimulation of granulocytic cell iodination by tannins and related compounds.

Tannic acid stimulated the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN) and human promyelocytic leukemic HL-60 cells, without affecting the iodination of 9 other cultured cell lines. The stimulation of both PMN and HL-60 cells depended on incubation time and temperature, and was significantly suppressed by myeloperoxidase inhibitors. Among chemically defined natural polyphenols, condensed tannins (epicatechin gallate oligomers) and monomeric and oligomeric hydrolyzable tannins potently stimulated PMN iodination, whereas polyphenols of lower molecular weight (gallic acid, alkyl gallates, epicatechin, epicatechin gallate, epigallocatechin, caffeic acid derivatives and licorice flavonoids) had much less activity. Various synthetic polyphenolic compounds structurally unrelated to tannins also stimulated PMN iodination depending upon their molecular weight, but to a slightly lesser extent. The results suggest that the stimulation activity of tannins and related polyphenols might depend more on their molecular weights than the number of hydroxyl groups on each benzene ring in the molecule, or the presence of sugars or hexahydroxydiphenoyl groups.

Animals↗

PubMedDate not supplied

Stimulation of human peripheral blood polymorphonuclear cell iodination by PSK subfractions.

A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr.) Quel, stimulated the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN), human promyelocytic leukemic HL-60 cells and human myeloblastic leukemic ML-1 cells. In contrast, PSK did not significantly increase the iodination of other cultured cell lines (U-937, THP-1, L-929, T98G, BALB 3T3). The PSK stimulation of iodination of both PMN and HL-60 cells depended on incubation time and temperature, and was significantly suppressed by the presence of myeloperoxidase inhibitors. Among various PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD), or the fraction precipitated at pH 4.0-4.5, stimulated the iodination most. In contrast, natural and chemically modified glucans had little or no stimulation activity. The active PSK subfractions synergistically enhanced TNF stimulation of PMN iodination. The data suggest the presence of some unique components in PSK which directly stimulate the iodination of myeloperoxidase-positive cells.

Animals↗

PubMedDate not supplied

Chemical modification potentiates paramylon induction of antimicrobial activity.

Induction of antimicrobial activity by two water-insoluble polysaccharides, paramylon and TAK, was significantly potentiated by introduction of positively charged groups (such as N,N-dimethylaminoethyl; N,N-diethylaminoethyl; and 2-hydroxy-3-trimethylammoniopropyl), but not by introduction of negatively charged groups (such as carboxymethyl or sulfate). Cross-linking of these derivatives with epichlorohydrin did not increase their potentiating activity. The effects of these derivatives did not always correlate with their ability to accumulate polymorphonuclear cells and to stimulate the generation of luminol-dependent chemiluminescence by peritoneal exudate cells.

Animals↗

PubMedDate not supplied

Induction of antiparasite activity by pine cone lignin-related substances.

Pretreatment with two distinct lignin-related antitumor substances extracted from pine cone of Pinus parviflora Sieb. et Zucc. protected infant mice from Hymenolepis nana (Cestoda) infection. Subcutaneous administration of these fractions (10 mg/kg) to 1 week old mice evoked strong protective immunity against oral infection by Hymenolepis nana eggs. Significant antiparasite effects were also induced in 4 week old mice by intraperitoneal or oral administration of these fractions. These fractions had more potent antiparasite activity than pine cone extracts with lower antitumor and antiviral activity, and various polysaccharides derived from plants and bacteria.

Animals↗

PubMedDate not supplied

Inhibition of herpes simplex virus infection by pine cone antitumor substances.

Several antitumor substances extracted from cones of various pine trees inhibited the plaque formation of Herpes simplex virus types 1 and 2 (HSV-1, HSV-2) strains in African green monkey kidney cells and human adenocarcinoma cells. The 50% effective dose of the most active fraction, Fr. VI (0.3 micrograms/ml) was 0.001 times its 50% cytotoxic dose (greater than 300 micrograms/ml). The anti-HSV activity of various pine cone extracts increased with their acidity. Identification of the polyphenol groups as donors of the acidity was further supported by the observation that the anti-HSV activity of the natural polyphenolic products, such as tannin and lignin, significantly exceeded that of other natural or chemically modified antitumor polysaccharides. An experiment using radiolabeled virus particles indicated that the anti-HSV effect of both Fr. VI and lignin was attributable to interference with virus adsorption to these cells rather than to inhibition of virus penetration into the cells.

Animals↗

PubMedDate not supplied

Molecular species of the antitumor and antiviral fraction from pine cone extract.

The most active fraction (Fr. VI) of antitumor and antiviral pine cone extract was subjected to chemical structure analysis. IR, UV, and ESR spectroscopies, in addition to chromatographic analysis on cellulose-TLC plates, reveal that the major component of Fr. VI includes structures belonging to the lignin family. A commercial alkali-lignin showed antiviral activity and granulocyte iodination stimulating activity as effective as those of Fr. VI, but had much weaker immunopotentiating activities, such as antitumor and antimicrobial activities and splenocyte stimulating activity. As a tentative conclusion, the active principle of Fr. VI might be complex(s) of lignin-like polyphenolic skeleton with a molecular matrix of unknown components.

Animals↗

PubMedDate not supplied

Mitogenic activity of pine cone extracts against cultured splenocytes from normal and tumor-bearing animals.

An acidic pine cone extract, Fr. V. of Pinus parviflora Sieb. et Zucc. significantly stimulated DNA synthesis of isolated splenocytes from both mice and rats, but only marginally affected the DNA synthesis of leukemic cell lines. The maximum stimulation level attained by Fr. V slightly exceeded that of plant lectins, whereas much weaker stimulating activity was found in natural and chemically modified antitumor polysaccharides, sialic acid-rich glycoproteins, and polyphenolic compounds such as lignin and tannic acid. In mice with subcutaneously transplanted sarcoma-180, responses of splenocytes against Con A declines in the terminal stage of tumor development, whereas responses against Fr. V remained relatively constant throughout all periods of tumor progression. The suppression of Fr. V activity by acetylation or methylation suggests the importance of the hydroxyl group in the expression of its stimulation activity.

Animals↗

PubMedDate not supplied

Induction of antimicrobial activity by antitumor substances from pine cone extract of Pinus parviflora Sieb. et Zucc.

Pretreatment with two distinct antitumor substances extracted from pine cone of Pinus parviflora Sieb. et Zucc. protected mice from the lethal effects of E. coli infection. Intraperitoneal administration of these fractions transiently induced differentiation-inducing factor (DIF) with a peak at 1-2hr. The rapid decay of DIF activity from the peritoneal cavity was followed by polymorphonuclear cell (PMN) accumulation and enhancement of superoxide generation (assayed with luminol-dependent chemiluminescence (LDCL] by peritoneal exudate cells. The superoxide generation by adherent cells was similarly enhanced by pretreatment, but was only 10-20% of that of the peritoneal exudate cells. Fractions that showed comparable antitumor/antimicrobial activity were also obtained from seed shells and cones of other pine trees of Japanese and foreign origin. On the other hand, a neutral polysaccharide fraction from Pinus parviflora Sieb. et Zucc. that lacked any of these activities did not induce PMN accumulation, DIF activity or LDCL generation. The results suggest a significant role in PMN activation for the expression of antimicrobial activity induced by pine cone extracts.

Animals↗

PubMedDate not supplied

Antitumor activity of polysaccharide fractions from pine cone extract of Pinus parviflora Sieb. et Zucc.

Hot water extract of pine cone (PCE) of Pinus parviflora Sieb. et Zucc. dose-dependently suppressed both solid and ascites tumor cells transplanted into various mice. Acidic polysaccharides of PCE significantly increased the survival time of mice bearing ascites tumor cells, and activity increased with acidity. One of the four polysaccharide fractions obtained by NaOH extraction showed the most potent antitumor activity. This fraction significantly suppressed the growth of solid tumor cells, with occasional tumor regression and necrosis, and with little or no cytocidal effect on cultured tumor cells. All acidic polysaccharides were able to activate mouse macrophage-like cell line J774.1. There did not appear to be any correlation between the antitumor activity of these polysaccharides and their content of arabinose (or fucose), mannose, galactose, glucose, or uronic acid.

Animals↗

PubMedDate not supplied

Hypochlorite scavenging activity of polyphenols.

Chemiluminescence, generated by the mixture of sodium hypochlorite solution and luminol, was completely eliminated by polyphenols, such as natural lignins, phenylpropenoid monomers and polymers, and epigallocatechin gallate. On the other hand, hypochlorite scavenging activity of polysaccharides, such as PSK (Krestin) and Schizophyllan, was relatively weak. Human myelogenous leukemic cell lines (HL-60, ML-1) showed higher production of active oxygen(s) (detected by luminol chemiluminescence) and iodination capacity, than six other cultured cell lines. Since lignin did not completely eliminate the active oxygen production by HL-60 cells, possible stimulation of hypochlorite production by lignin was suggested.

Antineoplastic Agents↗

PubMedDate not supplied

Stimulation by epigallocatechin gallate of interleukin-1 production by human peripheral blood mononuclear cells.

(-) Epigallocatechin gallate (EGCg) potently stimulated the production of interleukin-1 (IL-1) and tumor necrosis factor by human peripheral blood mononuclear cells. The intracellular amounts of IL-1 beta and especially IL-1 alpha induced by EGCg, were significantly higher than their extracellular counterparts. ECCg stimulated the production of adherent cells, with IL-1 producing capacity (per cell basis) that was significantly higher than nonadherent cells. Although IL-1 alpha mRNA synthesis (assessed by Reverse Transcriptase-Polymerase Chain Reaction) was slightly enhanced, IL-1 beta mRNA synthesis was not significantly enhanced by EGCg treatment. Lipopolysaccharide (LPS) also stimulated the production of IL-1 alpha and IL-1 beta production, but failed to induce the adherent cells. These data suggest that EGCg and LPS stimulate mononuclear cells by different mechanisms.

Antineoplastic Agents↗

PubMedDate not supplied

Stability of sodium 5,6-benzylidene-L-ascorbate.

The stability of sodium 5,6-benzylidene-L-ascorbate (SBA), consisting of two diastereomers, was investigated by high-performance liquid chromatography. In extensively acidic buffer, the acetal in SBA was immediately cleaved to liberate ascorbic acid and benzaldehyde. At higher pH, the cleavage of SBA was significantly reduced, but the degradation (due to possible opening of the lactone ring) of SBA was stimulated. The degradation rate of SBA was significantly increased with increasing temperature, and was higher than that of ascorbic acid or benzaldehyde. SBA was degraded with incubation time in culture medium, with accompanying loss of its biological activity, but only a marginal concentration of benzaldehyde, but not of ascorbic acid, was produced from SBA. The amount of SBA extracted from the apoptosing leukemic cells by 70% acetonitrile amounted to about 0.04% of that present in the medium fraction. These data suggest that SBA itself, but not contaminating ascorbic acid nor benzaldehyde, is responsible for the antitumor activity of SBA.

Antineoplastic Agents↗

PubMedDate not supplied

Endonuclease activity and induction of DNA fragmentation in human myelogenous leukemic cell lines.

When four human myelogenous leukemic cell lines (HL-60, ML-1, U-937, THP-1) were exposed to either ascorbic acid, hydrogen peroxide, etoposide, tumor necrosis factor, hyperthermia or UV irradiation, their growth inhibition and oligonucleosome-size DNA fragmentation were induced. Non-myelogenous leukemic cell lines (MOLT-4, K-562) were similarly sensitive to ascorbic acid and hydrogen peroxide, but relatively resistant to etoposide, TNF, hyperthermia and UV irradiation. Furthermore, these treatments except for UV irradiation, did not induce any apparent DNA fragmentation in MOLT-4 and K-562 cells. An autodigestion experiment revealed that all of these six cell lines contained divalent cation-independent endonuclease activity as a major endonuclease. The ability of this endonuclease to produce oligonucleosome-size DNA fragmentation was stimulated at acidic, but not at neutral pH. Since this enzyme activity was not detected in the lysosomal enzyme-free nuclei, prepared from all six cell lines, the cytoplasmic localization of this enzyme was suggested. The results suggest that the endonuclease activity might be differently regulated between myelogenous and non-myelogenous leukemic cell lines.

Apoptosis↗

PubMedDate not supplied

Rat hepatocellular carcinogenesis and proliferating cell nuclear antigen expression induced by 3'-methyl-4-dimethylaminoazobenzene.

The experimental conditions for the induction of rat hepatocellular carcinoma by oral administration of 3'-methyl-4-dimethylaminoazobenzene (DAB) were established. Hematoxylin-eosin (HE) staining of the liver sections revealed that precancerous lesions, characterized by small proliferation nest, hyperplastic nodule, oval cell and adenofibrosis, were observed 2 months after DAB administration. The highest incidence of hepatocellular carcinoma, trabecular carcinoma and mixed form of hepatocellular and cholangiocarcinoma was observed after 3-5 months and remained for an additional 2 months, even if the rats were continuously fed with DAB-free fodder. Immunohistochemical study with monoclonal antibody against proliferation cell nuclear antigen (PCNA) revealed that the relative number of PCNA-positive cells increased with the progress of the carcinoma. The present study confirms the previously reported usefulness of the PCNA immunostaining method for prognosis and assessment of the malignancy of carcinoma.

Animals↗