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YOSHIKI HAMADA, ISAO TAKEUCHI, MINORU HIROTA
1971 Volume 19 Issue 9 Pages
1751-1755
Published: September 25, 1971
Released on J-STAGE: March 31, 2008
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1, 8-Naphthyridines (III to VI) were synthesized in a high yield by the reaction of 2-aminopyridines with glycerol, in the presence of sodium m-nitrobenzenesulfonate, in sulfuric acid. Methylation of naphthyridines with dimethyl sulfoxide in the presence of sodium hydride or potassium tert-butoxide afforded their monomethyl or dimethyl compounds. This methylation with methylsulfinyl carbanion was examined from the Huckel molecular orbital method and its result agreed well with experimental results.
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AKIRA TAHARA, YASUO OHTSUKA, NORIHIDE UMINO, KAZUO NAGASAWA, KENICHI H ...
1971 Volume 19 Issue 9 Pages
1756-1767
Published: September 25, 1971
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Synthesis of 6β-hydroxy (acetoxy)-enantio-podocarpan-oic acid type compounds (e.g. V, VII ; XIV, XVI and XV, XVIII) were herein accomplished. These compounds are regarded as starting materials for examination of a notable epimerization at a lactonization. Furthermore, it is interesting that they have basic skeleton of many natural diterpenoids having C
6-oxygen function.
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AKIRA TAHARA, YASUO OHTSUKA
1971 Volume 19 Issue 9 Pages
1768-1785
Published: September 25, 1971
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Previously, it was found that a remarkable epimerization (βC
6-O→α) was occurred when 6β-hydroxy acid (II) was lactonized. In order to further examine on the mechanism and the limitation of the epimerization, the corresponding hydrogenated 6β-hydroxy acids (V, XIV and XXX) were chosen as model. One of them (XXX) was completely different, however the other (V and XIV) were epimerized as similar to (II).
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TAKASHI SUZUKI, MITSUHARU TAKEDA, HIROYA TANABE
1971 Volume 19 Issue 9 Pages
1786-1788
Published: September 25, 1971
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Extensive investigation of mycotoxin-producing fungi on and in Japanese foods has been carried out in our institute. About fifteen hundred strains were isolated from more than five hundred samples of various kinds of foods. Two strains of them were proved to produce aflatoxins. New metabolite was isolated from one strain of Aspergillus clavatus (WF-38-11) found in wheat flour and named ascladiol.
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SEIGORO HAYASHI, MITSURU FURUKAWA, YOKO FUJINO, HIDEJI MORISHITA
1971 Volume 19 Issue 9 Pages
1789-1793
Published: September 25, 1971
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N-Amidinoamidine reacted with diethyl oxalate in alcohol to give alkyl 4-amino-6-substituted sym-triazine-2-carboxylate through the formation of the intermediate. Regarding the structure of the intermediate, some considerations were afforded. N-Amidino-amidine also reacted with ethyl N-alkyloxamate to give 4-amino-6-substituted symtriazine-2-N-alkylcarboxamide, which was also obtained by the reaction of alkyl 4-amino-6-substituted sym-triazine-2-carboxylate with amines.
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TETSUJI KAMETANI, TETSUYA KOHNO, KAZUO KIGASAWA, MINEHARU HIIRAGI, KIK ...
1971 Volume 19 Issue 9 Pages
1794-1799
Published: September 25, 1971
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Grignard reaction of 5, 6, 7, 8-tetrahydro-2-methylphthalazinium iodide (IX) with 4-methoxybenzylmagnesium chloride afforded 1, 2, 5, 6, 7, 8-hexahydro-1-(4-methoxybenzyl)-2-methylphthalazine (X), which was further converted to several kinds of 1-benzylocta-hydrophthalazine derivatives (IV, XI, XII, XIII, XIV, XVII, and XIX). Grewe cyclization of IV to yield 16-azamorphinan (III) resulted in failure.
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JUICHIRO SHIBASAKI, RYOJI KONISHI, YOSHINORI TAKEDA, TAMOTSU KOIZUMI
1971 Volume 19 Issue 9 Pages
1800-1808
Published: September 25, 1971
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Pharmacokinetics on the formation and the excretion of the conjugates following rapid intravenous injection of N-acetyl-p-aminophenol (NAPA) was investigated in rabbits. In conflict with the assumption made by Nelson and Morioka in man that each excretion of the NAPA conjugates (glucuronide and sulfate) after dosage of NAPA would be rate-limited by each formation step, it was confirmed in rabbits that the formation step of the conjugates progressed much more rapidly than the subsequent excretion step. Furthermore, making a simplification that the two NAPA conjugates might be treated single since the glucuronide is predominant, the model fitting to the blood levels of free NAPA and the conjugate and the excreted amounts of the conjugate in the urine was elucidated, which consisted of a three-step consecutive first order process, the first step of which was the formation of the conjugate, the second the transfer of the conjugate from the blood to a hypothetical compartment, and the third urinary excretion of the conjugate through the intervenient compartment and two competitive first order processes, respectively, for the second step of the three-step consecutive process mentioned above and the direct urinary excretion of the conjugate from the blood.
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TOSHIHIKO OKAMOTO, HIROSHI TAKAHASHI
1971 Volume 19 Issue 9 Pages
1809-1814
Published: September 25, 1971
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The reaction of 3-nitroquinoline 1-oxide with potassium cyanide in methanol was carried out producing 3-methoxycinchoninonitrile 1-oxide (I) and 3-methoxy-1H-pyrazolo [4, 3-b] quinoline-9-carboxamide (II). 5-Nitroquinoline 1-oxide gave 5-methoxyquinoline-6-carbonitrile 1-oxide (XIII) and 7-aminoisoxazolo [3, 4-f] quinoline 1-oxide (XIV), whereas 6-nitroquinoline 1-oxide gave methyl 5-cyano-6-methoxyquinaldimidate 1-oxide (VI), 5-cyano-6-methoxyquinaldamide 1-oxide (VII), and 1-hydroxy-6-nitrocarbostyril (VIII) by the similar type reactions. 4-Nitroquinoline 1-oxide produced 4-methoxyquinoline 1-oxide.
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KIYOSHI IKEDA, WATARU URANO, KOZO HAMAGUCHI, KAZUO KUBO, HARUAKI YAJIM ...
1971 Volume 19 Issue 9 Pages
1815-1819
Published: September 25, 1971
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The circular dichroism of a number of active fragments of α-melanocyte-stimulating hormone was studied. It was suggested that the peptides studied have no distinct secondary structure.
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YASUO INUBUSHI, MASAHIKO KITANO, TOSHIRO IBUKA
1971 Volume 19 Issue 9 Pages
1820-1841
Published: September 25, 1971
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The synthesis of dl-cepharamine (4) which is a member of hasubanan alkaloids, was accomplished after the model experiments started from 2-tetralone (5) were examined. The keto-lactam (30) was synthesized from 7, 8-dimethoxy-2-tetralone (7) via the keto-ester (27) or the keto-nitrile (53). Ketalization of the compound (30), followed by treatment under the Wolff-Kishner reaction condition caused by demethylation of a methoxyl group at C
4 to result in the phenolic compound (63). Acetylation of the compound (63), followed by deketalization gave the keto-acetate (65). The diketone (67) was synthesized by bromination of the compound (65) with two equivalents of bromine, followed by heating with anhydrous sodium acetate in acetic acid. The target molecule, dl-cepharamine (4), was synthesized from the diketone (67) by successive treatments with BF
3·ether-MeOH (monoenolmethylation), LiAlH
4 reduction and oxidation with DMSO-phosphoric acid-DCC.
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YOSUKE OHKURA, YOSHIHIKO WATANABE, TSUTOMU MOMOSE
1971 Volume 19 Issue 9 Pages
1842-1848
Published: September 25, 1971
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A revised fluorimetric method for the determination of hexose with 5-hydroxy-1-tetralone was established which uses cupric sulfate as an accelerator of the fluorescence reaction, on the basis of the study on the effects of usual inorganic ions on the fluorescence reaction and the fluorescing reaction mixture. This method is very sensitive and is not affected by pentose and other organic compounds than hexose, and so may be useful for determining microamount of hexose in biological materials.
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MITSUJI YANAI, TOSHIO KINOSHITA, HIROSHI WATANABE, SUSUMU IWASAKI
1971 Volume 19 Issue 9 Pages
1849-1856
Published: September 25, 1971
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New pyrimido [4, 5-c] pyridazines were synthesized by cyclization of 3-amino-4-carbamoylpyridazines (IV, VII) and 3-chloro-4-ethoxycarbonylpyridazine (II). When 3-chloro-5-hydroxypyrimido [4, 5-c] pyridazine (XVI) was treated with phosphorous oxychloride and N, N-dimethylaniline, 1, 4-dihydro-3, 5-dichloro-4-(4'-N, N-dimethylaminophenyl) pyrimido-[4, 5-c] pyridazine (XX) was obtained, the structure was established by nuclear magnetic resonance spectra of dechlorination and hydrolysis products. Amination of XX affored 3-chloro-5-amino compounds.
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YOSHIKI HAMADA, ISAO TAKEUCHI
1971 Volume 19 Issue 9 Pages
1857-1862
Published: September 25, 1971
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1, 5-Naphthyridine (I) and 1, 8-naphthyridines (III to VI) were synthesized by the reaction of 3-or 2-aminopyridines with glycerol, in the presence of sodium m-nitroben-zenesulfonate, boric acid, and ferrous sulfate, in sulfuric acid. Application of the same method to 3-and 4-aminoqinolines afforded 4, 6-phenanthroline (VIII) and 5-methyl-1, -6-phenanthroline (IX). 1, 6-Naphthyridine (II) was obtained in a high yield by the reaction of 4-aminopyridine and glycerol, in the presence of sulfo-mix, boric acid, and ferrous sulfate.
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TAKESHI OISHI, MIWAKO MORI, YOSHIO BAN
1971 Volume 19 Issue 9 Pages
1863-1870
Published: September 25, 1971
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The reaction of thioanisol with acetyl chloride in the presence of SbCl
5 was attempted hoping the isolation of acetylsulfonium cation (V). The product actually obtained was found to be the sulfonium ion (IXa), which was also isolated from thioanisol and SbCl
5 without using acetyl chloride. The same type of compounds (IXb, XII, and XIV) was obtained in an analogous fashion. The mechanism of these reaction has been discussed. When dialkyl sulfides were treated with benzoyl chloride in the presence of AgClO
4, the expected benzoyldialkylsulfonium ions were isolated. The reaction of these salts with nucleophiles has also been described.
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TAKESHI OISHI, MIWAKO MORI, YOSHIO BAN
1971 Volume 19 Issue 9 Pages
1871-1875
Published: September 25, 1971
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The alkylation of thiono esters by [chemical formula], S^
-bCl
6 was carried out at low temperature and the corresponding S-alkylated species were isolated. The thermal stability of these salts has been discussed and their reactions with several nucleophiles have also been described.
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HIDEYO SHINDO, ISAO TAKAHASHI, EIICHI NAKAJIMA
1971 Volume 19 Issue 9 Pages
1876-1885
Published: September 25, 1971
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The distributions of
14C-labeled decamethonium, hexamethonium and dimethonium in mice after intraperitoneal injection were compared by whole-body autoradiographic technique and the results discussed in relation to the progressive change in the structure and to the pharmacological effect. The rate and the extent of accumulation in the liver was increased in the order of di-<hexa-«decamethonium. Decamethonium was found to be accumulated in the liver soon after injection in an extremely high concentration, which was retained for more than 72 hr. The excretion was mainly through the urinary route and the rate was in the order of di->hexa->decamethonium. As a common feature for the bisquaternary ammonium, the all compounds showed a rapid accumulation and a long retention in the cartilage and hexa-and decamethonium in the meninges, possibly in the arachnoid. No penetration was detected in the brain parenchyma. The all bisquaternary structure did not show any accumulation in the salivary gland and other secretory glands, where monoquaternary structure appears to be accumulated. Only decamethonium, a muscle relaxant, showed a high accumulation in the muscular tissues, while hexamethonium, a ganglionic depressant, as well as dimethonium which is inert pharmacologically did not show any accumulation. These results and a finding that tetraethylammonium, another ganglionic depressant, did not show any accumulation might indicate a presence of a direct relation between the distribution of a drug in macro level and the appearence of the pharmacological action.
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TOHRU KIKUCHI, TOSHINARI NISHINAGA, YOHKO YOSHIMURA
1971 Volume 19 Issue 9 Pages
1886-1892
Published: September 25, 1971
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Pachysandrine-A (Ia), -B (Ib), -C (II) and epipachysandrine-A (III), steroidal alkaloids of Pachysandra terminalis SIEB. et ZUCC. (Buxaceae), were formally synthesized from ergosterol.
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TOHRU KIKUCHI, TOSHINARI NISHINAGA, SHOICHIRO UYEO, OKIHIRO YAMASHIRO, ...
1971 Volume 19 Issue 9 Pages
1893-1899
Published: September 25, 1971
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Pachystermine-A (I) and-B (II), isolated from Pachysandra terminalis SIEB. et ZUCC. (Buxaceae), are novel type alkaloids having a β-lactam ring system in the molecule. These were synthesized from epipachysandrine-A (III) which was obtained as a minor component from the same source.
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HARUAKI YAJIMA, NORIO SHIRAI, YOSHIAKI KISO
1971 Volume 19 Issue 9 Pages
1900-1904
Published: September 25, 1971
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As model compounds, related to ferredoxin, two pentapeptides, H-Ser-Cys(Bzl)-Val-Ser-Cys (Bzl)-OH and H-Ser-Ser-Val-Ser-Ser-OH were synthesized.
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HARUAKI YAJIMA, HIROKI KAWATANI
1971 Volume 19 Issue 9 Pages
1905-1913
Published: September 25, 1971
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As an example of peptide-fragment condensation on the polymer support, coupling reaction between Z (OMe)-Val-Lys (Z)-Val-Tyr-Pro-OH (positions 19 to 24 of ACTH) and H-Asp (OBzl)-Gly-resin and H-Ala-Gly-resin was performed. Among various coupling reagents so far examined, N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline gave relatively good results.
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SHIGEO IWAHARA, KIMIE YANAGIMACHI, SHOZO KAMIYA, MASAHIRO NAKADATE, IK ...
1971 Volume 19 Issue 9 Pages
1914-1918
Published: September 25, 1971
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A concurrent test for the mutagenicity and the prophage-inducing activity of 1-alkyl-3-nitro-1-nitrosoguanidines (II) was carried out. In mutagenicity test, mutation from streptomycin-dependent to streptomycin-nondependent in E. coli Sd 4 was tested, and in prophage-induction test, induction of lambda-phage in E. coli K12 was used. 1-(2-Chloroethyl)-3-nitro-1-nitrosoguanidine (CNNG) showed the most potent mutagenicity, though the mutagenicity of 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) was remarkably high in comparison with those of other 1-alkyl-3-nitro-1-nitrosoguanidines (II : R=C
2-9). While, in prophage-inducing activity, n-propyl (II : R=n-C
3H
7) and n-butyl (II : R=n-C
4H
9) derivatives were most effective, showing larger induction index than MNNG and CNNG. When the alkyl chain became longer than C
5, both activities were extremely weakened.
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THOMASF. BRENNAN, ELI SHEFTER, PHYLLIS SACKMAN
1971 Volume 19 Issue 9 Pages
1919-1924
Published: September 25, 1971
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The solid state structure of a 1 : 1 homosulfanilamide : Sulfathiazole adduct was determined by single crystal X-ray diffraction. The results showed that the acidic proton of sulfathiazole is abstracted by the aminomethyl group of homosulfanilamide to form a salt. Intramolecular hydrogen bonds are also involved in the stabilization of this "molecular compound".
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TAKASHI MORISHITA, NOBORU YATA, AKIRA KAMADA, MASARU AOKI
1971 Volume 19 Issue 9 Pages
1925-1928
Published: September 25, 1971
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Studies were made of the effects of buffer components (phosphate-citrate isotonic buffer) on absorption of sulfonamides and of a reconfirmation was established of the equation presented previously in reference to an intestinal absorption of drugs. Absorption of sulfonamides from phosphate-citrate isotonic buffer of pH 5.8 decreased following preperfusion with pH 3.3 or 7.6 isotonic buffer, while it was not decreased when pretreated with Tyrode's solution. Dilution of phosphate-citrate isotonic buffer with 0.9% NaCl, whose pH was adjusted by a continuous titration of 0.1N HCl or 0.1N NaOH resulted in an enhancement of the increase. It was concluded that when phosphate or citrate ions were used as perfusion medium possible influences on the intestinal mucous membrane should be considered. When phosphate-citrate isotonic buffer was used, pH for maximum absorption did not correspond with pH for the maximum fraction of undissociated drug molecules, but when 0.9% NaCl whose pH was adjusted was used as perfusion medium, pH-profile of absorption corresponded with that of the undissociated fraction of drugs. Regarding such correspondence further study seems necessary in under way.
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AKIRA YASUMURA, HISASHI MURATA, KENJI HATTORI, KEIICHI MATSUDA
1971 Volume 19 Issue 9 Pages
1929-1936
Published: September 25, 1971
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^14C-Oxazolam (10-chloro-2, 3, 5, 6, 7, 11b-hexahydro-2-methyl-11b-phenylbenzo [6, 7]-1, 4-diazepino [5, 4-b]-oxazol-6-one), randomly labeled with
14C in the 11b-phenyl ring, was administered orally to the rat, and a number of metabolites were detected in the extracts of liver, kidney, brain, blood, urine and feces by thin-layer chromatography. Among those metabolites, N-desmethyl diazepam, oxazepam and 2-(2-hydroxy-n-propylamino)-acetylamino-5-chlorobenzophenone (PACB) were isolated from the liver extracts, 7-chloro-1, 3-dihydro-5-(4-hydroxyphenyl)-2H-1, 4-benzodiazepine-2-on (CDHB) from the bile, and 2-amino-5-chlorobenzophenone (ACB), 2-amino-5-chloro-3-hydroxybenzophenone (ACHB) and ACHB glucuronide from the urine. On the basis of these findings, a possible metabolic pathway of oxazolam was discussed.
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TOSHIO NAMBARA, JUNICHI GOTO
1971 Volume 19 Issue 9 Pages
1937-1942
Published: September 25, 1971
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The titled compounds have been synthesized from 13α-dehydroepiandrosterone (I) as outlined in Chart 1. The Grignard reaction of I with ethynylmagnesium bromide gave two epimeric 17-ethynyl-17-ols (IIa, VIIa), which on hydration were led to 17-hydroxy-13α-pregn-5-en-20-ones (IIIa, VIIIa), respectively. On catalytic hydrogenation these 5-dehydro compounds were transformed into the 5α-saturated derivatives (IIIc, VIIIc). The metal hydride reduction, usual acetylation followed by the Serini reaction afforded C-17 epimeric 3β-acetoxy-5α, 13α-androstane-3β, 17-diol diacetates (VI, XIb) employing the Baeyer-Villiger reaction. In the analogous manner IIIa and VIIIa were converted into the corresponding 13α-pregn-5-en-20-ones (Va, Xa).
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YOSHIKO KOMATSU, TATSUZO FUJII
1971 Volume 19 Issue 9 Pages
1943-1948
Published: September 25, 1971
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Calcium ions were found to stimulate the Na
+-K
+-sensitive ATPase as well as Mg
2+-ATPase (Na
+-K
+-insensitive ATPase) activities of human erythrocyte membrane in a concentration between approximately 0.04-0.4mM, and to inhibit them in a concentration higher than 4 mM. In the presence of Ca ions, the Na
+-K
+-ATPase activity dose not correspond to the ouabain-sensitive ATPase activity anymore which is apparently inhibited with increasing concentration of Ca ions. The effects of Ca
2+ on the Mg
2+-ATPase seems to be dependent on the ratio of Ca
2+/Mg
2+ concentrations. Erythrocyte stroma previously in contact with CaCl
2 and then washed, showed increased Mg
2+-ATPase activity when assayed in the absence of added Ca
2+ in the incubation mixture, with the maximal level of the activity almost equivalent to the maximal Ca
2+-Mg
2+-ATPase activity. This would mean that the Ca ions absorbed on the outer surface of the erythrocyte membrane is well capable of stimulating the ATPase activity. Normal values of these ATPase activities of human erythrocyte stroma were established. The ATPase of porcine erythrocyte membrane were similarly stimulated by Caions, whereas those of bovine erythrocyte were only slightly stimulated by this divalent cation.
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SHUNICHI NAITO, IPPEY SHIMIZU, SHIRO IWAKI
1971 Volume 19 Issue 9 Pages
1949-1956
Published: September 25, 1971
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HIROMU SAKURAI, AKIRA YOKOYAMA, HISASHI TANAKA
1971 Volume 19 Issue 9 Pages
1956-1958
Published: September 25, 1971
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TETSUJI KAMETANI, CHIZUKO SEINO, TAKUO NAKANO
1971 Volume 19 Issue 9 Pages
1959-1962
Published: September 25, 1971
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KIYOSHI HATA, MITSUGI KOZAWA, KIMIYE BABA, HYUNGJOON CHI, MASAO KONOSH ...
1971 Volume 19 Issue 9 Pages
1963-1967
Published: September 25, 1971
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SHIGERU TAKANASHI, YOSHIKAZU HINOHARA, YASUYO WATANABE, MASASHI OKADA
1971 Volume 19 Issue 9 Pages
1967-1970
Published: September 25, 1971
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TSUTOMU SUGASAWA, TATSURO TOYOTA, KAZUYUKI SASAKURA, TETSURO HIDAKA
1971 Volume 19 Issue 9 Pages
1971-1974
Published: September 25, 1971
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HIROSHI MITSUHASHI, KOJI TOMIMOTO
1971 Volume 19 Issue 9 Pages
1974-1978
Published: September 25, 1971
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HIROSHI HIKINO, MASARU OGURA, TSUNEMATSU TAKEMOTO
1971 Volume 19 Issue 9 Pages
1980-1981
Published: September 25, 1971
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