Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Volume 17 , Issue 7
Showing 1-28 articles out of 28 articles from the selected issue
  • Myung Ja CHOI, Boris M. GOROVITS, Jeongeun CHOI, EunYoung SONG, Kyung ...
    1994 Volume 17 Issue 7 Pages 875-880
    Published: July 15, 1994
    Released: April 10, 2008
    JOURNALS FREE ACCESS
    A visual membrane enzyme immunoassay is described for the measurement of methamphetamine in urine. To increase assay sensitivity, tracers with chemically similar structures were cross-checked with the antibodies to determine their influence on the antibody binding. Tracers of horseradish peroxidase-labeled methamphetamine (MA-HRP) and amphetamine (A-HRP) derivatives were prepared for this purpose. Significant differences in antibody specificity were found between the two tracers. Based on the results of this study, a pair of an antibody and a tracer was selected and a membrane enzyme immunoassay (EIA) was developed utilizing the competitive binding between methamphetamine and the drug-HRP tracer. UltraBind membrane (0.45μm) was used as the solid matrix to which the antibody was attached. Using diaminobenzidine substrate with Co2+ ion, a stable grey color appeared on the surface of membrane for MA-negative urine samples. No color appeared for MA-positive urine with a cut-off level of 0.8 ppm.
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  • Yoshitada KIMURA, Kiyoshi ZAITSU, Yuji MOTOMURA, Yosuke OHKURA
    1994 Volume 17 Issue 7 Pages 881-885
    Published: July 15, 1994
    Released: April 10, 2008
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    Of the examined dicarboxylic acid anhydrides, 3, 4, 5, 6-tetrahydrophthalic anhydride was found to be the best reagent in practical use for reversible amino-protection of insulin in terms of the rapidity of acid-deprotection. Twelve Gly (A1), Phe (B1), Lys (B29)-triacyl-insulins were prepared by reaction of porcine insulin with the dicarboxylic acid anhydrides and time courses for the deprotection of the acylated insulins with dilute acetic acid were investigated by means of capillary zone electrophoresis, and the tetrahydrophthalyl (THP)-insulin obtained with the reagent was the most rapidly deacylated (6h, 25°C, 0.1M acetic acid). Isolation of triacyl-insulins and Gly (A1)-THP-, Gly (A1), Phe (B1)-diTHP- and Gly (A1), Lys (B29)-diTHP-insulins using DEAE anion-exchange high-performance liquid chromatography is also described.
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  • Yasuhiro KOHAMA, Takayuki KURODA, Kentaro IIDA, Susumu ITOH, Tsutomu M ...
    1994 Volume 17 Issue 7 Pages 886-888
    Published: July 15, 1994
    Released: April 10, 2008
    JOURNALS FREE ACCESS
    The effect of tuna muscle-derived angiotensin-converting enzyme (ACE) inhibitory peptide (tuna AI) on the production of potent contracting factor, endothelin-1 (ET), in the cultured bovine aorta endothelial cells (BAECs) has been investigated. ET production in the culture medium was measured by radioimmunoassay. BAECs spontaneously produced ET in a time-dependent manner for 4 to 24h after incubation. Addition of tuna AI to the medium resulted in a time- and concentration-dependent decrease in the production of ET. The tuna AI-induced inhibition of ET production was blocked by B-3824 (bradykinin (BK) B2-receptor antagonist), NG-monomethyl-L-Arg and indomethacin, but not by angiotensin II receptor antagonist. While BK, sodium nitroprusside and platelet-derived growth factor (PDGF) significantly inhibited ET production, angiotensin II and interleukin-1 did not. Potent ACE inhibitory peptides among tuna AI analogues did not always inhibit ET production. The results suggest that tuna AI inhibits ET production at least in part in via potentiation of PDGF expression in addition to potentiation of BK pathway.
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  • Yasuhiro KOHAMA, Masahiko ITOH, Keishi TANAKA, Taro SENBA, Susumu ITOH ...
    1994 Volume 17 Issue 7 Pages 889-893
    Published: July 15, 1994
    Released: April 10, 2008
    JOURNALS FREE ACCESS
    We have found a new compound from thermophile extracts which inhibits antigen presentation on mouse macrophages. The substance inhibits the expression of the class II major histocompatibility molecule (Ia). It was extracted from Bacillus stearothermophilus UBT8038 and purified by silica gel column chromatography. The isolated inhibitor, Fr. 8-A, was a phosphatidylethanolamine with isofatty acids and chemically different from any of the natural or synthetic products which have been reported to modify Ia expression. Fraction 8-A inhibits Ia expression by mouse peritoneal macrophages induced by the supernatant from concanavalin A stimulated spleen cell cultures in a dose-dependent fashion over the range 0.1-10 μg/ml. This fraction also exhibited inhibitory effects on antigen presentation by splenic macrophages in vitro and on the mixed leukocyte reaction. The present results show that Fr. 8-A has a unique inhibitory effect on antigen presenting cells.
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  • Genichiro OSHIMA, Yasuhito NAKAGAWA
    1994 Volume 17 Issue 7 Pages 894-897
    Published: July 15, 1994
    Released: April 10, 2008
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    Diabetes was induced in rats by the intravenous administration of streptozotocin (STZ; 60 mg/ml). The activity of cholesterol esterase (CEase) in various tissues was determined by use of either a fluorogenic or radioactive substrate. Significant CEase activity was detected in extracts of pancreas. The specific activity of pancreatic CEase was considerably greater in pancreatic extracts from diabetic rats compared with normal rats. The activity of pancreatic CEase increased 6 d after the injection of STZ, but the difference was not statistically significant. It reached a maximum value approximately twice that of normal pancreas at 30 d with statistic significance. The highest specific activity of pancreatic CEase was found in the cytosolic fraction from diabetic rats, whereas the specific activity of the enzyme was lowest the same fraction from normal rats.
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  • Surachai UNCHERN, Koichi NAGATA, Hiroshi SAITO, Jun FUKUDA
    1994 Volume 17 Issue 7 Pages 898-901
    Published: July 15, 1994
    Released: April 10, 2008
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    The presence of piperine in a serum-free medium for 72 h markedly inhibited the neurite extension of cultured hippocampal and septal neurons under both high and low density cell culture conditions (initial cell density was 105 cells/cm2 and 2.5×103 cells/cm2, respectively). The average length of neurites decreased over a concentration range of piperine (12.5-100μM), and the distribution of neurite population shifted towards the shorter neurite lengths whereas an increase in the soma size was observed only with high piperine concentrations (75 and 100 μM, in a high density cell culture). This indicates that the piperine effect was relatively selective to the neurite extension. The neurite extension in low density cell cultures was considerably more susceptible to piperine than that in high density cell cultures (hippocampus : EC50=39 versus 113μM, septum : EC50=48 versus 101μM, in the low and high density cell cultures, respectively). This difference may be due to a lack of neurotrophic supports from non-neuronal cells under the low density cell culture condition. These findings suggest that piperine, in addition to its cytotoxic effect on the neuronal survival, suppresses the neurite extension in developing neurons.
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  • Katsuya HIGO, Akira KARASAWA
    1994 Volume 17 Issue 7 Pages 902-906
    Published: July 15, 1994
    Released: April 10, 2008
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    We tested the hypothesis that the abolition of the cyclic flow reduction (CFR) in the canine carotid artery is related to inhibition of ex vivo platelet aggregation following administration of KW-3635, a thromoxane A2 receptor antagonist, or aspirin. The CFR was induced in the carotid artery of anesthetized dogs by mechanical injury and narrowing of the artery. After induction of CFR, KW-3635 or aspirin was administered every 30 min at doses of 0, 1, 0.3, 1 and 3 mg/kg (i.v.). The ex vivo platelet aggregation, induced by sodium arachidonate and collagen, was also examined before and 15 min after each administration. KW-3635 and aspirin, at doses of 1 mg/kg i.v. and above, inhibited CFR and ex vivo platelet aggregation. These results suggest that CFR in the canine carotid artery is platelet-dependent.
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  • Kazuhiro IMAI, Sakae HIGASHIDATE, PabloRuano PRADOS, Tomofumi SANTA, S ...
    1994 Volume 17 Issue 7 Pages 907-910
    Published: July 15, 1994
    Released: April 10, 2008
    JOURNALS FREE ACCESS
    Three types of calcium antagonists, diltiazem, verapamil and nicardipine, were separately infused into Sprague-Dawley (SD) rats (under pentobarbital anesthesia n=5) through the left femoral vein at four different flow rates. Mean arterial blood pressure, heart rate and the concentration of plasma catecholamines (CAs), epinephrine (E), norepinephrine (NE) and dopamine (DA), were measured for each calcium antagonist, and the correlations between them were studied. Blood samples were collected within the infusion from common juglar vein. Plasma concentrations of CAs were determined by a HPLC-ethylenediamine condensation reaction-peroxyoxalate chemiluminescence detection system (HPLC-ED-PO-CL). The plasma concentration of CAs increased corresponding to the blood pressure reduction. The reduction induced by each calcium antagonist correlated with the logarithm of plasma NE concentration. The relation was expressed as Y=-α log X+m (Y, blood pressure; X, concentration of plasma NE; α, slope; and m, intercept). The correlation coefficients (rs) were -0.950 (diltiazem), -0.975 (verapamil) and -0.978 (nicardipine) (versus -0.734 for control). The α for nicardipine (108.4) was greater than those of diltiazem (85.4) and verapamil (80.8) (versus 31.0 for control), meaning that blood pressure reduction was greater in the case of nicardipine than diltiazem and verapamil, with an identical increment of plasma NE concentration. These data indicate that the contribution of the sympathetic nervous system to maintaining blood pressure reduced by nicardipine is less than that observed following the infusion of diltiazem and verapamil. Similar good inverse correlations between blood pressure and the logarithm of plasma concentration of E were observed with the three drugs infused (γ=-0.928, -0.966 and -0.948 for diltiazem, verapmil and nicardipine, respectively). A slight correlation (γ=-0.810) was obtained between blood pressure and the logarithm of plasma DA concentration following the infusion of nicardipine. On the infusion of nicardipine, the heart rate remained at the same value as the starting point during the first and second dose infusion (0.50 and 1.01 μg/kg/min, respectively) and was then reduced significantly after the additional infusions (2.02μg/kg/min), whereas the heart rates started to decrease from the first point of treatment with diltiazem and verapamil.
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  • Masaki ICHIKAWA, Hiromichi NAKAMUTA, Takashi HOSHINO, Yasunao OGAWA, M ...
    1994 Volume 17 Issue 7 Pages 911-913
    Published: July 15, 1994
    Released: April 10, 2008
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    The anti-osteopenic effect of nasal salmon calcitonin (SCT) was investigated in a type 1 osteoporotic model, Wistar rats which were ovariectomized (OVX) at age of 12 weeks, and compared with that of subcutaneous SCT. It was proved that nasal (5, 10, 20 and 40 U/rat) and subcutaneous (5, 10 and 20 U/kg) administration of SCT on alternate days for 3 weeks, starting a week after OVX, prevented the osteopenic changes of tibia and lumbar vertebra; this was proved by physicochemical parameters and histomorphometrically. A clear dose-dependent effect was seen in the trabecular bone volume of a selected regions of the 5th lumbar vertebra, and the ED50s of nasal and subcutaneous SCT calculated were 7.4U/rat and 3.5U/kg, respectively. The results indicate that nasal SCT is absorbed effciently in rats with increased bone turnover to prevent rapidly developing osteopenia and that the administration route is a suitable standard method for chronically giving biodegradable anti-osteoporotic peptides to rats.
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  • Takeshi ICHO, Shuji KOJIMA, Kazumori YOSHIKAWA, Tomoaki YOSHIMURA, Mas ...
    1994 Volume 17 Issue 7 Pages 914-916
    Published: July 15, 1994
    Released: April 10, 2008
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    We investigated the inhibitory effects of neopterin (NP) and its reduced form, 5, 6, 7, 8-tetrahydroneopterin (NPH4), on carbon tetrachloride (CCl4)-induced hepatotoxicity. In in vivo experiments, intraperitoneal administration of NP or NPH4 significantly inhibited the elevation of plasma alanine aminotransferase activity induced by CCl4 in mice. In in vitro experiments using cultured rat hepatocytes, CCl4 induced in a manner which was both time- and dose-dependent lactate dehydrogenase release, and the addition of NP or NPH4 to the culture-medium significantly inhibited its release from cells. NPH4, but not NP, reacted directly with a stable radical, 1, 1-diphenyl-2-picrylhydrazyl. These results suggest that NP and NPH4 inhibit CCl4-induced hepatotoxicity through different mechanisms.
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  • Koichi METORI, Sigeki OHASHI, Shushichi TAKAHASHI, Toshitake TAMURA
    1994 Volume 17 Issue 7 Pages 917-920
    Published: July 15, 1994
    Released: April 10, 2008
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    We evaluated the effects of Du-Zhong leaf extract on the serum and liver lipids in rats fed a high-fat diet supplemented with animal fat, cholesterol and cholate. The Du-Zhong leaf extract suppressed significantly the high-fat diet-induced increases in total serum cholesterol, serum triacylglycerol and hepatic triacylglycerol but not the total hepatic cholesterol. The Du-Zhong leaf extract also suppressed the high-fat diet induced increases in very-low density lipoprotein and low density lipoprotein without affecting high density lipoprotein cholesterol. These results suggest that Du-Zhong leaf extract may be beneficial for the regulation of hyperlipidemia.
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  • Tomoaki YOSHIMURA, Chikako KURITA, Futoshi YAMAZAKI, Satoshi NAKANO, H ...
    1994 Volume 17 Issue 7 Pages 921-926
    Published: July 15, 1994
    Released: April 10, 2008
    JOURNALS FREE ACCESS
    The lymphocyte stimulation test (LST) is useful for diagnosing drug-induced allergy and identifying the causative drug. In this study, we examined the usefulness of 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) as a marker for LST in diagnosing drug allergy. In a basic study using normal peripheral blood mononuclear cells, the normal range of stimulation index (SI) was 0.92-1.38, and the mean SI for all drugs tested was 1.134±0.111 (mean±S.D.). The cut-off value of SI for diagnosis of drug allergy was thus set at over mean + 2S.D. for possibly positive, and at over mean + 3S.D. as a definitely positive reaction. Forty-six cases of suspected drug-induced allergic hepatitis involving 85 drugs were diagnosed by this assay, and the possibly positive and definitely positive rates were 54.3% (SI≥1.4) and 41.3% (SI≥1.5), respectively. A clinical study was made of 113 patients with diagnosed drug-induced allergic hepatitis. Forty-nine (43%) of the patients were male and 64 (57%) were female. In 85% of cases the allergic reaction occurred within one month of taking medication, but there were a number of cases in whom onset occurred after long-term incubation. The main clinical symptoms were jaundice, itching, eruption, fever, and general malaise. In about 75% of cases glutamic oxaloacetic transaminase (GOT) or glutamic pyruvic transaminase (GPT) returned to normal range within one month after medication was halted. Among the causative drugs, antimicrobial agents were the most numerous accounting for 33.9% of the total, followed by central nervous system agents 21.2%, and cardiovascular agents 16.9%. These results indicate that LST with the MTT assay would be useful in diagnosing drug-induced allergic hepatitis, and that among the drugs examined, antimicrobial agents were responsible for the largest number of allergic reactions.
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  • Tatsuya ITO, Kana KOJIMA, Kinya KOIZUMI, Hiroyuki NAGANO, Takeshi NISH ...
    1994 Volume 17 Issue 7 Pages 927-930
    Published: July 15, 1994
    Released: April 10, 2008
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    Q-35, 1-cyclopropy-6-fluoro-1, 4-dihydro-8-methoxy-7-(3-methylaminopiperidine-1-yl)-4-oxoquinoline-3-car-boxylic acid, has excellent activity against gram-positive bacteria and inhibits S. aureus gyrase at concentrations more than 10-fold lower than those of other quinolones. In this paper, the effect of the C-7 and C-8 substituents of Q-35 on the inhibitory activity of gyrase purifled from S. aureus, M. luteus, E. coli, and P. aeruginosa are described. In addition, intracellular accumulation of Q-35 was examined. The 50% inhibitory concentrations (IC50) of Q-35, 8-fluoro-Q-35, and 8-hydro-Q-35 on DNA gyrase purified from S. aureus were 2.5, 7.8, and 68μg/ml, respectively. The IC50 on gyrase from P. aeruginosa were 11, 5.2, and 17 μg/ml, respectively. It is concluded that the introduction of a methoxy group into the 8 position of the quinolone leads to greater antibacterial activity against gram-positive bacteria. The concentrations of Q-35 which accumulated in S. aureus and E. coli were almost equal to ciprofloxacin, but in P. aeruginosa, Q-35 was lower than ciprofloxacin.
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  • Kazuyoshi SAGARA, Miwako KAWATA, Hiroaki MIZUTA, Masahiro SHIBATA
    1994 Volume 17 Issue 7 Pages 931-934
    Published: July 15, 1994
    Released: April 10, 2008
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    The utility of gastrointestinal physiology regulated-dogs (regulated-dogs) was evaluated in a bioavailability study. The gastrointestinal physiology of beagle dogs was regulated with a combined-treatment of intramuscular pentagastrin and intravenous atropine sulfate. Theophylline has been regarded as a drug that is absorbed completely in the entire gastrointestinal tract but slowly in the colon for humans. A commercial sustained-release tablet (SR tablet) of theophylline and a commercial conventional tablet of aminophylline (theophylline hemiethilenediamine salt) were chosen as model preparations in this study. In the regulated-dogs, the drug absorption was almost complete for the conventional tablet. The bioavailability of the SR table accounted for 76% in the regulated-dogs and 71% in intact dogs relative to that of the conventional tablet in the regulated-dogs, respectively, but no significant difference was detectable between these values. An advantage of the regulated-dogs over the intact dogs was, however, revealed in the time-profiles of the cumulative percentage of theophylline absorbed from the SR tablet, suggesting a modification of drug absorption by the prolonged arrival of the tablet to the colon.
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  • Atsushi NAGAYASU, Takashi SHIMOOKA, Yoshihito KINOUCHI, Kazuko UCHIYAM ...
    1994 Volume 17 Issue 7 Pages 935-939
    Published: July 15, 1994
    Released: April 10, 2008
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    The effects of fluidity and vesicle size on the antitumor activity and myelosuppressive activity of liposomes loaded with daunorubicin, an anthracycline antitumor drug, were investigated in Yoshida sarcoma-bearing rats. Liposomes composed of egg phosphatidylcholine (EPC) or hydrogenated egg phosphatidylcholine (HEPC), cholesterol and dicetyl phosphate in a molar ratio of 5 : 4 : 1 were injected intravenously into rats 5 d after subcutaneous inoculation of Yoshida sarcoma. At non-effect dosage in free drug, HEPC-liposomes with a diameter of 58 or 142 nm showed the greatest inhibitory effect against Yoshida sarcoma among liposomes tested, whereas larger ones (272 nm) had weaker effect. Small EPC-liposomes (57 nm) had no effect. Larger HEPC-liposomes (especially 142 nm) greatly decreased the number of peripheral white blood cell compared with free drug at the same dose, indicating relatively strong myelosuppressive toxicity. However, small EPC-and HEPC-liposomes with a diameter of 57 and 58 nm, respectively, showed toxic effects comparable to that of free drug. Examination of the dose-dependency of therapeutic effects and toxicity indicated encapsulation of daunorubicin in the small HEPC-liposomes to enhance the therapeutic index about 3 times that of free drug. These findings indicate the possibility of using small HEPC-liposome as a drug carrier for targeting solid tumors.
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  • Sayoko OSAKA, Hideki TSUJI, Hiroshi KIWADA
    1994 Volume 17 Issue 7 Pages 940-943
    Published: July 15, 1994
    Released: April 10, 2008
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    Previously, we synthesized 30-stearyl glycyrrhizin (GLOSt) and reported that small unilamellar liposomes containing GLOSt (GLOSt-SUV) accumulated in the liver several times more than the control liposomes (control-SUV). In the present study, to determine the interaction between GLOSt-SUV and hepatocytes, in vitro uptake experiments were achieved with primary cultured rat hepatocytes. The uptake amount of GLOSt-SUV by rat hepatocytes was considerably higher compared to the control-SUV, while GLOSt-SUV showed about a 10-fold higher uptake level than the control-SUV during 2 h of incubation. It was assumed that GLOSt-SUV not only bind to the surface of the hepatocytes but are internalized and degraded in the cells, because at 37°C, GLOSt-SUV were taken up and the level of the degradable marker was lower than the inert marker, and this did not occur at 4°C. Since the uptake of GLOSt-SUV was inhibited by glycyrrhizin (GL), it was suggested that a binding-site for GL is present on the surface of hepatocytes, and GLOSt-SUV are likely to be internalized via this site by the hepatocytes. Furthermore, it was confirmed that the efficacy of GLOSt on liposomes is not affected by the fluidity of the liposomal membrane.
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  • Koujirou YAMAMOTO, Yasufumi SAWADA, Tatsuji IGA
    1994 Volume 17 Issue 7 Pages 944-947
    Published: July 15, 1994
    Released: April 10, 2008
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    The relationship between the concentration of ambenonium (AMB), a selective and reversible acetylcholinesterase (AChE) inhibitor, in plasma and the potentiation of contractile muscle tension was investigated using a sciatic nerve-muscle preparation of rat. The developed isometric contraction was enhanced dose-dependently after i.v. administration of low doses (5-20 nmol/kg) of AMB, but the contraction was weakened when AMB was administered at high doses (100-1000nmol/kg), and the concentration-effect relationship was bell-shaped. The muscle contraction profile after 50nmol/kg administration without previous administration, with 20nmol/kg and with 50 nmol/kg administered previously were quite different from each other. These findings suggest that the potentiation of contractile muscle tension by AMB may be acutely tolerated and the concentration-effect relationship may change time-dependently.
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  • Jiro NEMOTO, Naohito OHNO, Kazuo SAITO, Yoshiyuki ADACHI, Toshiro YADO ...
    1994 Volume 17 Issue 7 Pages 948-954
    Published: July 15, 1994
    Released: April 10, 2008
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    OL-2, a highly branched (1→3)-β-D-glucan, is an antitumor glucan showing strong hematopoietic activity with weaker adjuvant activity than schizophyllan (SPG), another antitumor glucan and one which is used clinically. This paper deals with the gene expression of cytokines in mice by OL-2 and SPG in order to characterize their immunopharmacological activity. Gene expression was examined by a reverse transcriptase-polymerase chain reaction method after intraperitoneal administration of OL-2 or SPG (250μg/mouse). The OL-2 administered mice strongly expressed the interleukin 1 receptor antagonist (IL-1ra) gene but SPG administered mice did not. The difference would be strongly related to the antigen-specific response between OL-2 and SPG. In the genes related to haematopoiesis, OL-2 induced G-CSF and GM-CSF, but SPG induced IL-3. These differences would relate to the pattern of haematopoietic response. Comparing the cytokine gene expression in ICR and AKR mice by OL-2 administration, the changes in cytokine gene expression were less in AKR mice administered OL-2. These findings suggest that the immunopharmacological characteristics of OL-2 are closely related, at least in part, to the activation of the complement system. The data shown in this paper also suggest that cytokine gene expression by β-glucan would be significantly affected by the structure of these glucans.
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  • Masami KOJIMA, Naoyuki TSUTSUMI, Hideo NAGATA, Fumiaki ITOH, Arao UJII ...
    1994 Volume 17 Issue 7 Pages 955-959
    Published: July 15, 1994
    Released: April 10, 2008
    JOURNALS FREE ACCESS
    We have developed a simple model of osteopenia in rats which is induced by confinement without requiring surgical operation. Each rat was maintained for 8 weeks in a compartment of a commercially-available wire netting cage subdivided into 10 areas (compartment size, 9×16×14cm) to restrict exercise. The femora isolated from the confined rats showed significant decreases in mineral (calcium and phosphorus) content, compared with the level in normal rats, 2 weeks after the start of their confinement. Confined rats showed significantly lower values for the physical properties of bones such as breaking energy and breaking force and also density composed with normal rats 4 weeks after the start of confinement. KCA-098 (1mg/kg), a new benzofuroquinoline derivative that inhibits bone resorption and at the same time stimulates bone mineralization in organ culture, protected against these decreases when given orally for 8 weeks. All these results show that confinement of rats offers a simple and useful animal model of osteopenia.
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  • Shiro ISHIDA, Yoko SAKIYA, Zenei TAIRA
    1994 Volume 17 Issue 7 Pages 960-969
    Published: July 15, 1994
    Released: April 10, 2008
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    The dispostion of glycyrrhizin (GLZ) in the perfused liver of rats after dosing in the range of 0.5-30.0mg was investigated and a pharmacokinetic model was devised to interpret the results. The uptake rate of GLZ into the liver with respect to the unbound GLZ concentration (Cf) in the perfusate followed a Michaelis-Menten type equation with a Km, up of 1.17μg/ml and Vmax, up of 13.9μg/min/g of liver. The efflux clearance (0.044ml/min/g of liver) from the liver was independent of the Cf in the liver. The biliary excretion rate at a steady-state Cf level in the liver followed a Michaelis-Menten type equation with a substrate inhibition constant (Ki.B) of 42.3μg/ml, Km, B of 1.68μg/ml, and Vmax.B of 3.11μg/min/g of liver. The proposed model, with the holding time fitted to biliary excretion at each dose, accurately described both the perfusate concentration-time profile and the cumulative biliary excretion profile.
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  • Kazuo SAKAI, Jun NAKAJIMA, Morio NIIMURA, Riichiro UCHIDA, Yasuhiro YA ...
    1994 Volume 17 Issue 7 Pages 970-972
    Published: July 15, 1994
    Released: April 10, 2008
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    The main aim of this research was to investigate whether conformational alteration of polydeoxyguanylic-polydeoxycytidylic acid (poly [dG-dC]·poly [dG-dC]) by zinc acetate would have an effect on the binding of 1-nitropyrene (1-NP) to poly [dG-dC]·poly [dG-dC]. The binding of 1-NP to poly [dG-dC]·poly [dG-dC] in the hypoxanthine-xanthine oxidase system in vitro was increased by zinc acetate. This increase was abolished when EDTA was added to the preincubated mixture of poly [dG-dC]·poly [dG-dC] and zinc ions. Neither the production of 1-aminopyrene and its expected intermediates, N-hydroxy-1-aminopyrene and 1-nitrosopyrene, nor the 1-NP remaining in the reaction mixture was altered by the addition of zinc acetate without poly [dG-dC]·poly [dG-dC]. From these findings, it seems that the hypoxanthine-xanthine oxidase system is not activated by zinc acetate. On the other hand, under the same reaction conditions but the hypoxanthine-xanthine oxidase system and 1-NP, it has been reported that zinc ions or complexes transform the B-form of poly [dG-dC]·poly [dG-dC] to the Z-form. Therefore, these findings indicate that the formation of the Z-form or intermediates from the B-form by zinc ions may promote the binding of 1-NP to poly [dG-dC]·poly [dG-dC].
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  • Masashi TOMODA, Naoko OHARA, Noriko SHIMIZU, Ryoko GONDA
    1994 Volume 17 Issue 7 Pages 973-976
    Published: July 15, 1994
    Released: April 10, 2008
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    A novel β-heteroglucan, called cnidirhan SIIA, was isolated from the rhizome of Cnidium officinale MAKINO. It was homogeneous on electrophoresis and gel chromatography, and its molecular mass was more than 1×107. It was composed of D-glucose, D-galactose and L-arabinose in the molar ratio of 85 : 5 : 8, in addition to small numbers of O-acetyl groups. Methylation analysis and nuclear magnetic resonance studies indicated its main structural features composed of β-1, 6-linked D-glucopyranosyl residues with both 3, 6- and 4, 6-branching points. In addition, it has both β-1, 4-linked L-arabinopyranosyl and β-1, 6-linked D-galactopyranosyl residues. The polysaccharide showed very pronounced reticuloendothelial system-potentiating activity in a carbon clearance test, as well as a marked anti-complementary activity.
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  • Yoshikazu YUKI, Kazuo KATO
    1994 Volume 17 Issue 7 Pages 977-979
    Published: July 15, 1994
    Released: April 10, 2008
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    A specific sandwich enzyme-linked immunosorbent assay (ELISA) was developed for human growth hormone (hGH) with molecular weight of 22 kDa (22khGH). To prepare the 22k hGH specific antibody, a peptide (P-15) corresponding to residues 32-46 in 22k hGH was synthesized and used to immunize rabbits, because a 20k hGH variant was known to lack this peptide sequence. The assay method was developed using a combination of an anti P-15 polyclonal antibody (YK-2) coated on the microtiter well as a catching antibody and another polyclonal antibody against 22k hGH as a peroxidase-conjugated detecting antibody. The assay sensitivity was 1ng/ml for 22k hGH, and cross-reactivity with other pituitary protein hormones as well as the 20k hGH variant was less than 0.01%, respectively. Furthermore, the 22k hGH content was measured precisely even in the presence of 20k hGH in this ELISA system.
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  • Tadayori SHIMIZU, Yoshihisa IWAMOTO, Yasutake YANAGIHARA, Muneaki KURI ...
    1994 Volume 17 Issue 7 Pages 980-982
    Published: July 15, 1994
    Released: April 10, 2008
    JOURNALS FREE ACCESS
    Mitogenicity and the production of tumor necrosis factor (TNF) by a chemically synthesized lipotetrapeptide analog (KAB-8), S-[2, 3-bis (palmitoyloxy)-2R-propyl]-N-[(2, 2, 2)-trichloro-ethoxycarbonyl : Troc group]-(R)-cys-teinyl-(S)-seryl-(S)-seryl-(S)-asparagine, the amino acid sequence of which corresponds to that of the lipopeptide part of lipoprotein in Escherichia coli, and several derivatives (KAB-30-41), which possessed the altered glycerocysteine moiety, were examined. A 1-cysteinyl glycerol skeleton-type compound (KAB-8), a propane-type compound (KAB-31), a homoglycerol-type (KAB-39 and 40) and a 2-cysteinyl glycerol-type (KAB-41) exhibited mitogenic activity on splenocytes from C3H/He mice at various concentrations ranging from 0.4 to 100μg/ml. However, propane-type compounds. except KAB-31, and ethane-type compounds showed lower mitogenic activity than other types of compounds. Compounds KAB-8, 31, 40 and 41 induced the production of TNF in peritoneal exudated macrophages from C3H/He mice at concentrations of 25 and 50 μg/ml. The results indicate that the structural differences of the glycerol moiety in the synthetic lipopeptides affect the potency of its biological activities.
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  • Yoshiro SAITO, Takeshi YAMAZAKI, Kazuhiro SUZUKI, Hideharu IKEBUCHI, A ...
    1994 Volume 17 Issue 7 Pages 983-986
    Published: July 15, 1994
    Released: April 10, 2008
    JOURNALS FREE ACCESS
    Monoclonal anti-peptide antibodies against the extracellular domain of human growth hormone receptor (hGHR) were prepared. Four monoclonal antibodies (mAbs) reacted with an extracellular domain protein produced by genetic engineering. Among them, GHRP2-88 was the most reactive against hGHRs from human IM-9 cells. The lower limit of detection for immunoblotting using this mAb was about 200 pg hGHR. The GHRP2-88 antibody also reacted with deglycosylated hGHRs from tunicamycin-treated IM-9 cells and with the growth hormone-binding protein (GH-BP) in human plasma.
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  • Ken ARITA, Tsutomu ARAKI, Katsuro SHUTO, Masamichi SATOH
    1994 Volume 17 Issue 7 Pages 987-989
    Published: July 15, 1994
    Released: April 10, 2008
    JOURNALS FREE ACCESS
    We investigated the effect of vinconate on the long-term potentiation of population spikes following the stimulation of mossy fibers in the CA3 pyramidal layer of hippocampal slices from guinea pig brain. Vinconate (10-7 and 10-6 M) dose-dependently augmented the long-term potentiation in the mossy fiber-CA3 system. This effect was reduced by treatment with scopolamine at a concentration of 10-6 M, which showed no significant change in the long-term potentiation in a mossy fiber-CA3 system. These results suggest that vinconate may augment long-term potentiation in the mossy fiber-CA3 system partly via activation of the cholinergic system.
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  • HanSuk YOUNG, HaeYoung CHUNG, ChungKyu LEE, KunYoung PARK, Takako YOKO ...
    1994 Volume 17 Issue 7 Pages 990-992
    Published: July 15, 1994
    Released: April 10, 2008
    JOURNALS FREE ACCESS
    An attempt was made to isolate the active component of Eriobotrya japonica, which inhibits aflatoxin B1-induced mutagenicity in the Salmonella assay system. The number of revertants per plate was significantly decreased when a MeOH extract of Eriobotrya japonica was added to the assay system using Salmonella typhimurium TA100 or TA98. Furthermore, we examined the effect of each fraction purified from the MeOH extract, and an EtOAc fraction was found to be the most effective. Ursolic acid isolated from the EtOAc fraction markedly and significantly decreased the numbers of Salmonella typhimurium TA100 revertants per plate, thus showing antimutagenic activity.
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  • Riichiro UCHIDA, Shoichi TOKUTAKE, Yoshinori MOTOYAMA, Kenji HOSOI, No ...
    1994 Volume 17 Issue 7 Pages 993-995
    Published: July 15, 1994
    Released: April 10, 2008
    JOURNALS FREE ACCESS
    Taking advantage of selective α-amylase inhibition by O-6-deoxy-α-D-glucopyranosyl-(1→4)-O-α-D-glucopyranosyl-(1→4)-D-glucose, we developed a new inhibitor method for the differential assay of two human α-amylase isoenzymes.
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