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Biomedical subjects

D Mizuno

Publications and source records attributed to D Mizuno.

At least 19 recordsLinked to original sources
PubMed1992

Expression of transcripts of complement components and their receptors during differentiation of embryonal carcinoma cell lines.

Based on our previous finding that TNF-alpha and TNF-beta can be expressed constitutively during early embryonal development [1], we extended our work to identify factors which are generally known to take part in inducing inflammation in adults. They can be regarded as candidate molecules involved in ontogenic inflammation during embryonal development. In this study, we chose the factors which are constituents of either a classical or an alternative pathway of a complement system and found that mRNAs corresponding to those of C2, C3, C4, C5 and to those of receptors CR1 and CR2 were expressed. Among them, mRNA expression of C3, C4, and CR1 was especially constitutive. Contrary to these observations, expression of two kinds of scavenger receptors (SR-I, SR-II) proved to be negative. In this report, the framework of ontogenic inflammation as a regulatory mechanism in embryonal development at the molecular level is discussed.

Animals↗
PubMed1992

BRM activities of low-toxic Bordetella pertussis lipopolysaccharides.

A low-toxic lipopolysaccharide (BP-LPS) was isolated from killed Bordetella pertussis (Tohama strain). LD50 of BP-LPS was about 0.8 mg/mouse which was about 10-fold higher than the LD50 of E. coli-LPS(80 micrograms/mouse). Toxicity measured by decrease in body weight of BP-LPS-injected mice was similarly low. BP-LPS had strong antitumor activities against various murine syngeneic tumors, and its systemic administration caused clear regression of such as MM46 mammary carcinoma and Meth A fibrosarcoma. It is noteworthy that a tolerable dosage of BP-LPS (375 micrograms/mouse) showed clear antitumor activity against MH134 hepatoma, which is known to be insusceptible to usual types of BRM including bacterial LPS. These findings suggest that BP-LPS is a promising candidate as an antitumor agent for clinical use. Biological activities of BP-LPS were examined and compared with those of toxic LPS extracted from Escherichia coli and other enterobacteria. Activation or stimulation of macrophages and lymphocytes by these LPS, including TNF induction, was found to be similar. However, activation of human or murine neutrophils, as estimated by neutrophil-adherence assay in vitro, though induced by all other toxic LPS tested, was not induced by BP-LPS. This inability of BP-LPS to activate neutrophils is assumed to be related to its low toxicity.

Animals↗
PubMed1992

Homeostasis as regulated by activated macrophage. IV. Analgesic effect of LPSw, a lipopolysaccharide of wheat flour.

The effect of LPSw, a lipopolysaccharide from a water extract of wheat flour, on pain response was investigated using an acetic acid-induced writhing test in mice. LPSw inhibited writhing dose-dependently in the range of 10 ng-10 micrograms/mouse i.v. This effect reached its maximum 1.5-3 h after the LPSw inoculation and was detectable even after 8 h. The analgesic effect of LPSw was inhibited by i.v. injection of naloxone and also beta-endorphin was detected in serum and brain tissue following injection of LPSw. Preliminary clinical trials were done in which LPSw was administered percutaneously to relieve the pain of patients with herpes. The results showed that pain was relieved by this application. LPSw may be the best analgesic drug so far known, since it induces the endogenous mediator of analgesia, beta-endorphin.

Analgesics↗
PubMed1992

Homeostasis as regulated by activated macrophage. V. Suppression of diabetes mellitus in non-obese diabetic mice by LPSw (a lipopolysaccharide from wheat flour).

A lipopolysaccharide from wheat flour (LPSw) which was isolated and characterized is shown to exert definitely a suppressive effect on incidence of type 1 diabetes in mice. Therapeutic effect on type 2 diabetes in patients was also obtained, though only from preliminary results. The percutaneous route of administration is most favorable. The important role that precursor tumor necrosis factor, free or cell bound, may play in this mechanism is discussed.

Animals↗
PubMed1992

Homeostasis as regulated by activated macrophage. VI. Protective effect of LPSw (a lipopolysaccharide from wheat flour) against acute infection by Toxoplasma gondii in mice.

An oral administration of partially purified LPSw, a lipopolysaccharide (LPS) from wheat flour, at a concentration of 20 ng/ml in drinking water beginning 1d after infection significantly decreased mouse mortality and prevented animal weight loss in acute infection with Toxoplasma gondii. Whereas 71% (5/7) of mice in a control group that did not receive LPSw died of toxoplasmosis, only 14% (1/7) of mice treated with LPSw died (p less than 0.05). The administration of LPS purified from Bordetella pertussis also significantly decreased the mortality of infected mice. LPS from Escherichia coli and synthetic lipid A (LA-15-PP(506)), however, did not show a significant decrease in mortality.

Acute Disease↗
PubMed1992

Homeostasis as regulated by activated macrophage. VII. Suppression of serum cholesterol level by LPSw (a lipopolysaccharide from wheat flour) in WHHL (Watanabe heritable hyperlipidemic) rabbit.

The effect of LPSw (a lipopolysaccharide from wheat flour) on cholesterol catabolism was examined using WHHL (Watanabe heritable hyperlipidemic) rabbit, which is an experimental model of familial hyperlipidemia. The serum cholesterol level of the animal decreased by the addition of LPSw to drinking water. Following cessation of the addition of LPSw to the drinking water, the cholesterol level was decreased for 30 to 40d and then gradually elevated. The serum level of apolipoprotein B, which is a constituent of apolipoprotein of low density lipoprotein (LDL), also decreased in accord with serum cholesterol at a nearly coincident rate. Conversely, the level of apolipoprotein A-I, which is a constituent of apolipoprotein of high density lipoprotein (HDL), did not change, nor did HDL-cholesterol. Furthermore, the atherosclerosis risk factor, expressed as the ratio of apolipoprotein B to apolipoprotein A-I, was decreased by LPSw administration.

Animals↗
PubMed1992

Homeostasis as regulated by activated macrophage. VIII. LPSw (a lipopolysaccharide from wheat flour) can regulate bone resorption of chick embryo.

The effect of LPSw (a lipopolysaccharide from wheat flour) on the bone resorption of 18-d chick embryonic calvaria was examined in an organ culture following the method of Raisz. Bone was prelabeled in culture medium containing 45Ca and chased in a cold medium. On addition of test samples, labeled calcium was released indicating the grade of bone resorption. LPSw (10-100 ng/ml) stimulated bone resorption, showing an effect comparable to parathyroid hormone (PTH) (1 U/ml). PTH at 1 U/ml decreased the total amount of calcium and phosphorus, while LPSw did not. LPSw is thus assumed to stimulate bone resorption more actively than PTH.

Animals↗
PubMed1992

Homeostasis as regulated by activated macrophage. IX. Enhancement effect of LPSw (a lipopolysaccharide from wheat flour) on hen egg-laying and breaking strength of eggshell.

Oral administration of LPSw (a lipopolysaccharide from wheat flour) given at 60 micrograms/hen/d in drinking water, markedly enhanced eggshell strength. The monthly percentage of eggs laid with a shell strength of more than 4 kg to the total number of eggs was 32% in the group given LPSw in drinking water while it was 12% in the control group given plain water. At the same time, LPSw caused a 30% enhancement of total monthly number of eggs laid over that of control.

Animals↗
PubMed1992

Homeostasis as regulated by activated macrophage. I. Lipopolysaccharide (LPS) from wheat flour: isolation, purification and some biological activities.

Based on our new concept of ontogenic inflammation, we have sought a substance which can prime macrophage in terms of the endogenous production of tumor necrosis factor (TNF). A lipopolysaccharide (LPSw) was found in wheat flour, purified and characterized. The molecular size of LPSw was about 5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it contained 3-deoxy-D-manno-octulosonic acid: 1, hexosamine: 4 and one phosphorus in a single molecule. LPSw can prime macrophage to release TNF when given intradermally, percutaneously or even orally in mice as well as in humans, in exactly the same way as intravenous administration of interferon gamma.

Administration, Oral↗
PubMed1992

Homeostasis as regulated by activated macrophage. II. LPS of plant origin other than wheat flour and their concomitant bacteria.

In order to seek a macrophage-activating substance, lipopolysaccharide (LPS) of plant origin other than that of wheat flour was surveyed. A large amount of LPS (10-100 micrograms/g) was detected in Laminaria japonica (kelp), Curcuma longa (turmeric), Undaria pinnatifida and other substances. Since concomitant bacteria possibly existing in root of farm products can be considered to contribute to LPS of plant origin, a count was taken of bacterial cells both dead and alive. This count revealed that some LPS were derived from concomitant bacteria which had probably come from root. Few concomitant bacterial cells were found in seaweed, while stem-root contained enough bacterial cells. Three predominant bacteria have been isolated and identified; Pantoea agglomerans, Enterobacter cloacae, and Serratia ficaria. These LPSs were purified and their chemical compositions were examined. They are similar to that of Escherichia coli except that their molecular sizes are smaller. Since LPS is non-toxic when taken orally or percutaneously, these LPSs may also be advantageous in the cure of intractable diseases.

Animals↗
PubMed1992

Homeostasis as regulated by activated macrophage. III. Protective effect of LPSw (lipopolysaccharide (LPS) of wheat flour) on gastric ulcer in mice as compared with those of other LPS from various sources.

Protective effect of lipopolysaccharide (LPS) from various sources on gastric ulcer has been examined in mice using parenteral as well as oral route. Ulcer is induced by indomethacin, stress or alcohol. LPS was prepared from 6 species of bacteria (Escherichia coli, Pantoea agglomerans, Serratia ficaria, Enterobacter cloacae, Bordetella pertussis, Alcaligenes faecalis) and from wheat flour. When administered intravenously, LPS of Pantoea agglomerans was the most effective among other LPS examined. Lipopolysaccharide of wheat flour (LPSw) showed a significantly protective effect by the oral route, especially when given ad libitum in drinking water to mice.

Animals↗
PubMed1992

Oral or percutaneous administration of lipopolysaccharide of small molecular size may cure various intractable diseases: a new version of Coley's toxin.

Based on our new finding that an inflammation in which tumor necrosis factor (TNF) is primed or triggered (ontogenic inflammation) can regulate the homeostasis in ontogenesis, we have identified a new lipopolysaccharide from wheat flour (LPSw) that can induce ontogenic inflammation in adult mice. LPSw can prime adult mice to produce TNF when given orally or percutaneously, suggesting that it may maintain homeostasis in adults. LPSw can cure experimental animals of diabetes, hyperlipidemia, ulcer, and herpes. It can also stimulate bone resorption and egg-laying, and shows a strong analgesic effect that is blocked by naloxone. This effect even allows a release from drug addiction. Suppression of serum cholesterol level by oral uptake of LPSw in Watanabe heritable hyperlipidemic (WHHL) rabbit was also observed. Infection of toxoplasma was prevented by oral uptake of LPSw. The realization that a single oral or percutaneous administration of LPSw may be a cure for multiple intractable diseases may lead to the presentation of a nontoxic type of Coley's toxin, which is known to be an efficient cancer treatment, but has high toxicity.

Administration, Cutaneous↗
PubMed1979

Purification and preparation of antibody to RNA polymerase II stimulatory factors from Ehrlich ascites tumor cells.

An improved method was developed for purification of the protein termed S-II that specifically stimulates RNA polymerase II of Ehrlich ascites tumor cells. The specific activity of the final preparation was 400 000 units/mg of protein, which is about 30-fold higher than that of the previous preparation [Sekimizu, K., et al. (1976) Biochemistry 15, 5064]. The final preparation gave a single band on both sodium dodecyl sulfate and nondenaturing gel electrophoresis, and the protein extracted from the band on nondenaturing gel had stimulatory activity. S-II is a basic protein with a molecular weight of 40 500. The fundamental characteristics of S-II determined with the previous preparation were confirmed with completely purified S-II. A specific antibody to S-II was prepared. This antibody inhibited only the stimulatory activity of S-II and did not affect the activity of RNA polymerase II itself. Thus, S-II is probably not a component of the multimeric proteins of RNA polymerase II.

Animals↗
PubMed1979

Conservation of ribosomal fidelity during ageing.

The function of ribosomes prepared from the liver of young (2--5 months old) and senescent (15--26 months old) mice were compared in vitro. The conclusions that can be drawn from the liver of senescent mice is 10 to 40% lower than that of young mice; (2) the fidelity of translation does not change grossly with age; (3) the thermosensitivity of translational activity of ribosomes and the activity of ribosome-associated ribonuclease do not change with age; (4) there is an age-dependent accumulation of free 40S ribosomal subunits in the cytoplasm of mouse liver. The relation of age-dependent changes in the structure and function of ribosomes is discussed.

Aging↗