Biomedical subjects

Akira Murakami

Publications and source records attributed to Akira Murakami.

133 records · Page 8Linked to original sources

PubMedDate not supplied

Synergistic suppression of superoxide and nitric oxide generation from inflammatory cells by combined food factors.

In contrast to chemopreventive strategies using individual agents, a combination of specified compounds may be effectual to achieve desirable results with higher efficacy and lower toxicity. In the present in vitro study, we examined combinations of agents and assessed which concentrations were appropriate to yield notable synergism. L-N(G)-Monomethyl-L-arginine (L-NMMA), a synthetic inducible nitric oxide synthase (iNOS) inhibitor, and zerumbone, a natural sesquiterpene that suppresses iNOS de novo synthesis, were combined at various concentrations, with the aim to diminish combined lipopolysaccharide- and interferon-gamma-induced nitric oxide generation in a murine macrophage line, RAW264.7. Although the combinatorial effects (CEs) were antagonistic or additive at higher concentrations, significant synergism was obtained at lower concentrations where each agent alone did not cause significant inhibition. Similarly, the CEs were synergistic when (-)-epigallocatechin gallate (EGCG) and genistein were combined at lower concentrations, whereas those of two iNOS inhibitors, L-NMMA and L-N(G)-aminoethyl-L-ornithine, were either additive or antagonistic at all concentrations tested, suggesting that a combination of given agents with different action mechanisms is a prerequisite for synergistic effects. For suppression of phorbol ester-induced superoxide anion radical (O(2)*(-)) generation in differentiated HL-60 cells, the CEs of 1'-acetoxycahvicol acetate (ACA), a phenyl propanoid that suppresses O(2)*(-) generation, and O(2)*(-) dismutase were also synergistic, though only at lower concentrations. The CEs of ACA/EGCG were antagonistic or additive, even at low concentrations, suggesting that the signal transduction pathways triggered by these agents are antagonistic. The present findings suggest that individual food phytochemicals have complex interactions that can be antagonistic, additive, and/or synergistic in biological systems, depending upon certain environmental factors including concentrations. Further, these results support and emphasize the concept that combinations of different types of chemicals at low concentrations are one of the essential areas of study for chemopreventive strategies.

Animals↗

PubMedDate not supplied

Modifying effects of 1'-acetoxychavicol acetate (ACA) and the novel synthetic retinoids Re-80, Am-580 and Am-55P in a two-stage carcinogenesis model in female rats.

Effects of dietary administration of 1'-acetoxychavicol acetate (ACA) and the novel synthetic retinoids 4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (Re-80); 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]benzoic acid (Am-580); and 6-[(3,5-di-tert-butylphenyl) carbamoyl]nicotinic acid (Am-55P) were examined using a two-stage rat carcinogenesis model. A total of 190 female SD rats was treated sequentially with 1,2-dimethylhydrazine (DMH, s.c.); 7,12-dimethylbenz(a)anthracene (DMBA, i.g.); and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN, in the drinking water) during the first three weeks (DDD-initiation), and an additional 60 rats received the vehicle alone (non-initiation). One week after the completion of the initiation period, they were divided into nine groups and administrated Re-80 (at dose levels of 1.0 or 0.4 ppm), Am-580 (20 or 4 ppm), Am-55P (20 ppm), ACA (100 ppm), all-trans-retinoic acid (10 or 2 ppm) or no supplement in the diet for 33 weeks, until survivors were euthanatized at week 37 weeks. After DDD-initiation, all-trans-retinoic acid at the high dose delayed the development of mammary tumors. The multiplicity of colon tumors in the group fed Am-55P and the incidences of nephroblastomas with ACA or Am-580 were decreased as compared with the control values, but the other chemicals had no modifying effects on tumor development in any organs. Thus, among ACA and the novel synthetic retinoids tested, only Am-55P showed a weak inhibitory effect on a neoplasm of general interest under the present experimental conditions.

Administration, Oral↗

PubMedDate not supplied

Suppressive effects of mioga ginger and ginger constituents on reactive oxygen and nitrogen species generation, and the expression of inducible pro-inflammatory genes in macrophages.

We previously conducted screening tests of the chloroform extracts from a total of 89 species of Japanese plant food items for their suppressive effects on superoxide (O(2) ()) generation through both NADPH oxidase and xanthine oxidase, and reported that mioga ginger (Zingiber mioga Roscoe) indicated the strongest suppressive activities. In this study, the suppressive effects of mioga ginger constituents, aframodial, and galanal B, together with [6]-gingerol and galanolactone occurring in ginger, on free radical generation and inducible proinflammatory gene expressions were investigated. Of these constituents, aframodial (20 microM) exhibited marked suppressive effects on 12-O-tetradecanoylphorbol-13-acetate-induced O(2) () generation in HL-60 cells and lipopolysaccharide (LPS)/interferon-gamma-induced nitric oxide (NO) generation in RAW264.7 cells (inhibition rates [IRs]=84.6% and 95.9%, respectively). Aframodial also strongly suppressed the stimulated HL-60 cell-induced mutagenicity in AS52 cells (IR=95.9%). The LPS-induced expression of inducible proinflammatory genes such as inducible NO synthase, interleukin (IL)-1beta, IL-6, and granulocyte-macrophage colony-stimulating factor was significantly abolished (IRs=99.1%, 74.6%, 74.0%, and 64.4%, respectively) by aframodial. In addition, degradation of the inhibitor of nuclear factor kappaB was suppressed by this compound (IR=100%), suggesting that the suppression of nuclear factor kappaB activation, at least in part, is involved. Taken together, these results suggest that aframodial has potent antioxidative and anti-inflammatory potentials, and may be a promising candidate in prevention and/or therapy for chronic inflammationassociated carcinogenesis.

Animals↗

PubMedDate not supplied

Central retinal vein occlusion caused by human herpesvirus 6.

We describe a 1-year-old girl with central retinal vein occlusion caused by human herpesvirus 6. She received systemic corticosteroid therapy. Although there was retinal recovery after the therapy, the visual acuity in her left eye still could not be measured.

DNA, Viral↗

PubMedDate not supplied

Difference in prognostic factors between stage IB and II uterine cervical carcinoma patients treated with radical hysterectomy and postoperative radiation therapy.

PURPOSE: The purpose of the current study was to evaluate the difference in prognostic factors between stage IB and II uterine cervical carcinoma patients treated with postoperative radiation therapy. PATIENTS AND METHODS: Between May 1988 and May 1998, a total of 94 patients including 47 patients with stage IB and 47 patients with stage II uterine cervical carcinoma were treated with postoperative radiation therapy at Tokyo Metropolitan Komagome Hospital. All patients were treated with 10 MV X-rays using an anterior-posterior parallel opposed field which covered the whole pelvis. Fractionation was 2 Gy per day, five fractions per week, to a total dose of 50 Gy. RESULTS: The 5-year overall survival rates of stage IB and II were 89.4% and 79.3%, respectively. In multivariate analysis for all patients, lymph node status, histology, and surgical margin status were recognized as prognostic factors. Limited to stage IB patients, lymph node status was the only independent prognostic factor. However, for stage II patients, tumor histology was also an independent prognostic factor. CONCLUSIONS: The prognostic factors of stage IB and II were different. Tumor histology was only associated with stage II patients. These findings suggested that tumor histology might have played a different role as tumor stage progressed. However, further studies with large numbers of patients will be required to confirm these results.

Adult↗

PubMedDate not supplied

Growth inhibitory activities of crude extracts obtained from herbal plants in the Ryukyu Islands on several human colon carcinoma cell lines.

There is increasing interest in the use of herbs for the treatment of human diseases including cancer. Therefore, the purpose of this study was to determine whether crude extracts obtained from 44 herbal plants in the Ryukyu Islands might contain components capable of inhibiting the growth of a variety of human colon carcinoma cell lines. Leaves, roots and other parts of the plants were extracted with chloroform, and the crude extracts were dissolved in dimethylsulfoxide and used for the experiments. Extracts of Hemerocallis fulva, Ipomoea batatas, Curcuma longa, and Nasturium officinale caused marked dose-dependent growth inhibition, with IC(50) values in the range of 10-80 mug/ml. With the HCT116 cell line, the extracts of Hemerocallis fulva and Ipomoea batatas induced G1 cell cycle arrest after 48 h of treatment. In addition, we found that extracts of Curcuma longa, and Nasturium officinale induced apoptosis in these cells after 48 h of treatment. The present studies are the first systematic examination of the growth inhibitory effects of crude extracts obtained from herbal plants in the Ryukyu Islands. The findings provide evidence that several plants in the Ryukyu Islands contain components that may have anticancer activity.

Carcinoma↗

PubMedDate not supplied

Suppressive effects of Okinawan food items on free radical generation from stimulated leukocytes and identification of some active constituents: implications for the prevention of inflammation-associated carcinogenesis.

Okinawa prefecture in Japan is a distinct area characterized by unique traditional food habits and longevity. Prolonged exposure to activated leukocytes, playing pivotal roles in chronic inflammation-associated carcinogenesis, is known to lead to oxidative and nitrosative damage to macromolecules in the body since they are primary sources of free radicals, such as superoxide anion (O(2)(-)) and nitric oxide (NO). In this study, we estimated anti-oxidative and anti-nitrosative activities of Okinawan food items by employing two cellular experimental systems: (1) phorbol ester-induced O(2)(-) generation from differentiated HL-60 human promyelocytic leukemia cells; and (2) lipopolysaccharide (LPS)-induced NO generation in RAW264.7 murine macrophages. A total of 138 food items, consisting of 42 samples unique to Okinawa and 96 common in the Japanese main island, were purchased at local markets in Okinawa and extracted with chloroform. When tested at a concentration of 100 microg/ml, 38% (16/42) of the former showed 70% or more inhibition of O(2)(-) generation while 21% (20/96) of the latter did so. In parallel, 64% (27/42) of the former showed significant NO generation suppression in contrast to 48% (46/96) of the latter . Twenty-one active species were further tested at a concentration of 20 mug/ml, and eleven species, including sugar cane, wild turmeric, and zedoary, were indicated to be most promising items with anti-oxidative and anti-nitrosative properties. In addition, some of the active constituents (chebulagic acid, a resveratrol derivative, and sesquiterpenoids) were identified. Our results suggest that food items typical in the Okinawa area have higher cancer preventive potential than those common in Japan.

Animals↗