Biomedical subjects

H Sakagami

Publications and source records attributed to H Sakagami.

At least 253 records · Page 14Linked to original sources

PubMedDate not supplied

Relationship between pi-electron distribution and anticancer activity of benzo[a]phenothiazines.

In order to study the correlation between the anti-tumor activity of benzo[a]phenothiazines and the electron densities, the Huckel orbital method and modified-neglect-of-diatomic overlap (MNDO) orbital method were used. 9-Methyl-12H-benzo[a]phenothiazine (2), which showed the most potent anticancer activity among benzo[a]phenothiazines, had the highest charge of nitrogen atom (QN), L-region (QL) and M-region (QM) in the molecule. The other derivatives, which showed weaker anticancer activity, had a much reduced value of these charges (QN, QL, QM). The data suggest that stability of pi-electron in 1 benzene ring and 1 naphthalene ring in the benzo[a]phenothiazine skeleton might be responsible for the induction of anticancer activity.

Animals↗

PubMedDate not supplied

Anti-influenza virus activity of a lignin fraction from cone of Pinus parviflora Sieb. et Zucc.

When mice were inoculated intranasally or intracerebrally with lethal doses of influenza virus A/WSN/33, most died within 12 days. However, the infectivity of virus that had been preincubated with a lignin prepared from cones of Pinus parviflora Sieb. et Zucc. (PC-Fr. VI) was significantly reduced. Intraperitoneal or oral administration of PC-Fr. VI, prior to virus inoculation, slightly increased the survival ratio of the infected mice. Experiments using radiolabeled PC-Fr. VI revealed that this fraction effectively binds to virions as well as to cultured cells. These data suggest that PC-Fr. VI either inactivates the virus or induces the anti-viral state in cells by binding to virions or cells.

Administration, Oral↗

PubMedDate not supplied

Antimicrobial activity of phenothiazines, benzo[a]phenothiazines and benz[c]acridines.

The abilities of 14 phenothiazines, 8 benzo[a]phenothiazines and 12 benz[c]acridines to induce an antibacterial effect against Escherichia coli K12 were compared. Several phenothiazines, which showed antiplasmid activity, displayed the most potent antibacterial activity. All benz[c]acridine derivatives were moderately antibacterial, whereas benzo[a]phenothiazines were inactive. The active phenothiazine derivatives had more potent inhibitory activity against fungi, including phytopathogen filamentous, human pathogen filamentous fungi and yeasts, than against gram-positive and -negative bacteria. Taken together with previously reported data, the induction mechanism of antimicrobial and antiplasmid activity by these compounds seems to be different from that of antitumor, differentiation-inducing and carcinogenic activity.

Acridines↗

PubMedDate not supplied

Effects of Catuaba extracts on microbial and HIV infection.

Pretreatment of mice with hot water and alkaline extracts of Catuaba casca (Erythroxylum catuaba Arr. Cam.) effectively protected them from lethal infection of Escherichia coli and Staphylococcus aureus. The extracts significantly inhibited both the human immunodeficiency virus (HIV)-induced cytopathic effect and the expression of HIV antigen in HIV-1HTLV-IIIB or HIV-2ROD infected human lymphotropic virus type I (HTLV-1) positive MT-4 cells. The 50% effective concentrations of the active fractions (21-263 micrograms/ml) were 1/4 - 1/43 of their 50% cytotoxic concentrations. Their anti-HIV activity was shown to be induced, at least in part, via the inhibition of HIV adsorption to the cells. The data suggest a medicinal potential of Catuaba extracts against opportunistic infection in HIV patients.

Animals↗

PubMedDate not supplied

Antiplasmid activity of phenothiazines, benzo[a]phenothiazines and benz[c]acridines.

Various synthetic derivatives of phenothiazines, benzo[a]phenothiazines and benz[c]acridines were compared for their abilities to induce antiplasmid activity against E. coli F'lac plasmid. Several phenothiazine derivatives were much more potent in antiplasmid activity than benzo[a]phenothiazine- or benz[c]acridine derivatives. Their antiplasmid activity seemed to be enhanced by Cl- or CF3- substitution at 2 C atom, and modified by the side chain length and charge at the L-region of the molecules, as well as by hydrophilicity.

Acridines↗

PubMedDate not supplied

Stimulation of monocyte iodination and IL-1 production by tannins and related compounds.

Various tannins and related compounds were compared for their ability to stimulate the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood monocytes. The stimulating activity of most of the monomeric and dimeric hydrolyzable tannins was generally higher than that of the trimeric and tetrameric compounds. Compounds that had dehydrohexahydroxydiphenoyl or chebuloyl groups had considerably less activity than those that had other functional groups (hexahydroxydiphenoyl, valoneoyl, dehydrodigalloyl, isodehydrodigalloyl, lactonized valoneoyl, hellinoyl, euphorbinoyl, dehydroeuphorbinoyl or woodfordinoyl group). The methylated derivative, nonacosa-O-methylcoriariin A, was essentially inactive, suggesting the requirement of a phenolic hydroxyl group. Three condensed tannins ((-)-epicatechin 3-O-gallate (ECG)-dimer, ECG-trimer and ECG-tetramer) significantly stimulated both monocyte iodination and their interleukin-1-like factor production. The results suggest the dependence of stimulation of monocyte iodination by tannins and related polyphenols on molecular weight.

Animals↗

PubMedDate not supplied

Effect of pine seed shell extract on microbial and viral infection.

Pretreatment of mice with ammonia extract of seed shell of Pinus Koraicenis, via the intraperitoneal or intravenous route, effectively protected them from lethal infection of Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The pine seed shell extract also moderately inhibited syncytium formation and cytopathogenic effect induced by human immunodeficiency virus (HIV) infection in cultured human lymphotropic virus type I (HTLV-1) positive MT-4 cells. These data suggest a medicinal potential of pine seed shell extract against opportunistic infection in HIV patients.

Animals↗

PubMedDate not supplied

Antitumor, antiviral and immunopotentiating activities of pine cone extracts: potential medicinal efficacy of natural and synthetic lignin-related materials (review).

Several antitumor substances that effectively inhibited the growth of ascites and solid tumor cells transplanted in mice were isolated from pine cone NaOH extract by acid- and ethanol-precipitation. These antitumor substances were also potent antiviral agents against human immunodeficiency virus, herpes simplex virus and influenza virus; they induced antimicrobial activity against Staphylococcal aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, and induced antiparasite activity against Hymenolepis nana in mice. Chemical analysis of these substances by IR, UV, NMR, ESR and partition chromatography on cellulose-TLC plate disclosed that they had lignin-related structures complexed with sugars or polysaccharides. Chlorinated decomposition of the lignin portion significantly reduced their antiviral activity. In agreement with this, the antiviral activity of synthesized lignins prepared by polymerization of phenylpropanoid precursors was comparable to that of the undecomposed counterparts of the pine cone extract. Acid hydrolysis of the polysaccharide portion significantly reduced the ability of the substances to induce antitumor and antimicrobial activities in mice. With an appropriate eliciting agent, intravenous administration of natural lignified substances transiently induced endogenous production of a cytotoxic factor (possibly tumor necrosis factor) in normal mice. Their priming activity was significantly higher than that of their component units or degradation products. These data suggest the importance of conjugating lignins with polysaccharides for in vivo expression of various kinds of immunopotentiating activity. As possible explanations for their induction of a variety of immunopotentiating activities, these natural and synthetic lignins stimulated macrophage NBT-reducing activity, polymorphonuclear cell (PMN) iodination and splenocyte DNA synthesis and inhibited poly (ADP-ribose) glycohydrolase, RNA-dependent DNA polymerase (reverse transcriptase) and RNA-dependent RNA polymerase activities.

Adjuvants, Immunologic↗

PubMedDate not supplied

Cytotoxicity and differentiation-inducing activity of phenothiazine and benzo[a]phenothiazine derivatives.

The effects of 13 phenothiazines, and 8 benzo[a]phenothiazines on the growth and differentiation of various human cultured cell lines were investigated. Perphenazine dimaleate and chlorpromazine hydrochloride were more cytotoxic against human normal fibroblasts and glioma cells than 19 other related compounds. The differentiation of three human myelogenous leukemic cell lines (ML-1, U-937, THP-1) into maturing monocytes/macrophages was potently induced by 12H- benzo[a]phenothiazine and 5-oxo-5H-benzo[a]phenothiazine. The differentiation--inducing activity of phenothiazine, and other benzo[a]phenothiazine derivatives was much less, and that of phenothiazine derivatives without the benzyl group was undetectable. Simultaneous treatment with 12H- benzo[a]phenothiazine and tumor necrosis factor produced additive, but not synergistic differentiation--induction of these cells.

Cell Differentiation↗

PubMedDate not supplied

Induction of tumor degeneration by sodium benzylideneascorbate.

Intravenous administration of sodium benzylideneascorbate (SBA) rapidly necrotized inoperable human lung cancer, and induced degeneration of 3'-methyl-4-dimethylaminoazobenzene-induced rat hepatocellular carcinoma (vacuolar, eosinophilic degeneration, nuclear debris) without affecting the serum glutamic oxaloacetic transaminase, gamma-glutamyl transpeptidase and total protein levels. Cultured normal human lung and skin fibroblasts, and human glioma and glioblastoma cell lines were relatively resistant to SBA, when compared to human myelogenous leukemic cell lines. SBA had no apparent host immunopotentiation activity such as stimulation of cytokine action or production; activation of monocyte or polymorphonuclear cells; or modulation of poly (ADP-ribose) glycohydrolase activity. The data suggest that the antitumor activity of SBA might be produced by direct action of authentic SBA or its metabolized form(s), rather than by immunopotentiation of the hosts.

Animals↗

PubMedDate not supplied

Inhibition of tumor necrosis factor-stimulated human peripheral blood polymorphonuclear cell iodination by sera from various cancer patients.

Tumor necrosis factor (TNF) dose- and time-dependently stimulated the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN). The addition of sera obtained from patients with brain tumors, or gastric, pancreatic, hepatocellular, common bile duct or lung carcinoma significantly inhibited TNF-stimulated PMN iodination, whereas sera of normal volunteers were, in general, not inhibitory. TNF-stimulated iodination of human peripheral blood monocytes was almost eliminated by brain tumor patient sera, but was significantly enhanced by normal human sera. Specific [135I] TNF binding to the PMN receptors was significantly increased in the presence of either patient sera or normal sera. These data suggest some mechanism other than modification of TNF receptor binding for expression of the inhibitory action of cancer patient serum.

Adolescent↗

PubMedDate not supplied

Functional maturation of monocytes/macrophages induced by PSK subfractions.

When mouse resident peritoneal macrophages were cultured with PSK (Krestin), a protein-bound polysaccharide extracted from Coriolus versicolor, they became enlarged and elongated and expressed higher NBT-reducing activity. PSK stimulated the production of differentiation-inducing factor and cytotoxic factor by the mouse macrophage-like cell line J774.1, and iodination (incorporation of radioactive iodine into an acid-insoluble fraction) and interleukin-1-like factor production by human peripheral blood monocytes. Among four different PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD) was the most potent. Natural and chemically modified glucans had little or no activity. The data suggest that some unique structure of the highest molecular weight fraction of PSK directly stimulates the monocytes/macrophages.

Animals↗

PubMedDate not supplied

Macrophage stimulation activity of antimicrobial N,N-dimethylaminoethyl paramylon.

Pretreatment with N,N-dimethylaminoethyl (DMAE) paramylon significantly protected mice from infection by various microorganisms. When mouse peritoneal macrophages were cultured with DMAE-paramylon, they showed morphological change (spreading) and elevated NBT-reducing activity. Macrophages prepared from DMAE-paramylon-treated mice had higher NBT-reducing activity than those from control mice. On the other hand, carboxymethyl paramylon and paramylon sulfate, which did not induce appreciable antimicrobial activity, failed to stimulate macrophage functions. The data suggest a significant role of macrophages in antimicrobial activity induction by cationized glucans.

Animals↗

PubMedDate not supplied

Effect of sera of brain tumor patients on cytokine-induced human myelogenous leukemic cell differentiation.

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 (TNF), interferon-gamma (IFN-gamma) and interleukin-6. Serum of normal humans efficiently stimulated this cytokine-induced differentiation, whereas the stimulating effect of serum of brain tumor patients was much less. Both normal and patient sera, at effective concentrations, only slightly affected the binding of 125I-TNF to ML-1 cells, but any of these sera significantly inhibited the binding of 125I-IFN-gamma to U-937 cells or to THP-1 cells. These results suggest that the weak differentiation-stimulating effect of the serum of brain tumor patients cannot be explained simply by the modification of the binding of these cytokines to cellular receptors.

Adult↗

PubMedDate not supplied

Mitogenic activity of natural and synthetic lignins against cultured splenocytes.

Various natural lignified materials and synthetic dehydrogenation polymers (the so-called synthetic lignins) prepared from several phenylpropenoids were investigated for their mitogenic activity. All of these materials time- and dose-dependently stimulated the DNA synthesis of isolated mouse splenocytes. However, their stimulating activity was significantly decreased when the splenocytes were pretreated with anti-Thy-1.2 monoclonal antibody and rabbit complement. Natural and synthetic lignins demand attention as potential immunopotentiators.

Animals↗

PubMedDate not supplied

Stimulation of mouse peritoneal macrophages by lignin-related substances.

Various lignified materials, including pine cone extract and a commercial lignin, stimulated the morphological change (spreading) of mouse peritoneal macrophages, and their functional maturation as judged by increase in NBT-reducing activity. When these materials were treated with NaClO2 to decompose the phenolic structure, their activity was completely eliminated, whereas the activity was rather enhanced when they were treated with H2SO4 to decompose their sugar moiety. Some monomeric phenolic compounds structurally related to lignin components and several antitumor glucan derivatives had little or no macrophage stimulating activity. The results strongly suggest the importance of lignin-structure in macrophage activation.

Animals↗

PubMedDate not supplied

Induction of immunopotentiation activity by a protein-bound polysaccharide, PSK (review).

A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr.) Quel, has been recognized for its host-mediated induction of antitumor and antimicrobial activities in mice. Intravenous administration of PSK, in association with OK-432 (Picibanil), transiently induced endogenous production of a cytotoxic factor (CF) (possibly tumor necrosis factor, TNF) in normal mice. The ability to produce CF depended greatly on both dose and interval between administration of the PSK and OK-432. Although PSK has been reported to contain several active ingredients, unfractionated PSK has been used in almost all experiments performed so far. We recently reported that, of the four subfractions separated by successive filtration through membrane filters, only the highest molecular weight fraction F4 (MW greater than 200 kD) induced significant antimicrobial activity in mice. PSK stimulated the NBT-reducing activity of mouse peritoneal macrophages and the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN). Among the subfractions of PSK, the highest molecular weight fraction F4, and the fraction precipitated at pH 4.0-4.5 (Fr. 4), stimulated macrophage NBT-reducing activity and PMN iodination most. In contrast, natural and chemically modified glucans had little or no stimulating activity. PSK, F4 or Fr. 4 additively or synergistically stimulated TNF-induced cytotoxicity against L-929 cells, differentiation of human myelogenous leukemia cell lines toward monocytes/macrophages, and iodination of human peripheral blood PMN. The active PSK subfractions significantly reduced the down regulation of specific 125I-TNF or 125I-IFN-gamma binding to cellular receptors. These data suggest that (i) immunopotentiation activity of PSK might be ascribed, at least in part, to stimulation of cytokine action and production, and (ii) PSK might have some unique structural features.

Adjuvants, Immunologic↗

PubMedDate not supplied

Lignified materials as potential medicinal resources. II. Prevention of pathogenic bacterial infections in mice.

Antibacterial activity was demonstrated when ddY mice were intraperitoneally infected with E. coli or P. aeruginosa two days after a single ip-injection of a hot-water or alkaline extract obtained from lignified materials, such as chips of slash pine, Douglas fir, tallow wood, and two shelf fungi. Lignified material is a promising medicinal resource for the prevention and/or treatment of pathogenic microbial infection.

Animals↗