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The effects of voluntary exercise on the growth, glycogen of muscle and lipid contents of the liver and serum of mice fed different levels of dietary protein were investigated. In both the exercise and non-exercise groups, body weight gains were significantly greater in the 20% and 30% protein diet groups than in the 6% and 4% protein diet groups. After 6 weeks of age, it was shown that the amount of voluntary exercise by the 6% and 4% protein diet groups was greater than that by the 20% and 30% protein diet groups. As for hematological status, the raising of hemoglobin levels due to increasing dietary protein levels was further exaggerated by voluntary exercise. Hematocrit values rose with the increase in dietary protein levels. However the effect of exercise on hematocrit values was not clear. Liver glycogen levels, which were elevated with the increase in dietary protein levels, rose further due to exercise, though no changes were observed in muscle glycogen due to dietary protein levels and exercise. The lipid contents of the liver in all groups tended to be lower in exercise groups compared with non-exercise groups and it was observed that the high levels of dietary protein depressed the increase in liver lipids. Liver triglyceride levels of all groups fed the dietary protein levels except for the 20% casein diet group decreased due to voluntary exercise, and liver triglyceride levels were also lowered as dietary protein levels increased. The levels of serum triglyceride of all groups decreased due to voluntary exercise. This phenomenon was most remarkable in rats fed a 6% casein diet. The tendency for serum cholesterol levels to decrease due to increasing dietary levels of protein was further intensified by voluntary exercise. However it was not further influenced by voluntary exercise in the 4% casein diet group.

To see the influence of a restricted diet and a meal feeding for the growing Wistar rats were subjected to three types of feeding patterns, free access feeding, three meals and one meal per day. The animals of each feeding pattern group were fed either unrestricted and restricted amount of diet. The restricted group received only 60% weight of the diet taken by the unrestricted groups. The growth of the animals having free access to the restricted amount of diet was almost similar to that of those having received the restricted amount of diet three meals per day rather than to the group fed the unrestricted diet once per day. The former group seemed to be a "nibbler type" rather than a "meal feeder type".

約500日にわたる長期間の4%, 6%および20%たん白質食の摂取および自由運動がマウスの成長, 血清総コレステロール, 血清GPT活性, 脂肪組織重量および生存数に及ぼす影響について検討を行なった。また, 各食餌たん白レベル条件下の動物における運動量の推移についても観察を行なった。体重増加量は, 運動群および非運動群ともに, 食餌たん白レベルが高くなるほど大きく, 20%, 6%, 4%たん白群の順であった。自由運動量に関しては, 各食餌たん白レベルで特徴的な動きを示し, その運動量が減少し始める時期はたん白レベルが低いほど早かった。血清総コレステロールに関しては, 食餌たん白レベルが低いほど高値を示し, いずれの食餌群でも運動群のほうが非運動群よりも低かった。血清GPT活性については, 食餌たん白レベルおよび自由運動による影響は認められなかった。副睾丸脂肪組織重量については, いずれの食餌群でも運動群のほうが非運動群よりも顕著におさえられていた。6%たん白群と20%たん白群の運動群および非運動群の生存率は4%たん白群のものよりも高かった。

0～30%のセルロースを含む食餌を雄マウスに与え, 消化物残渣の滞腸時間, 糞水分含量, および消化管の長さ, 重量を測定し, 次の結果を得た。1) 胃の長さ, 重量はセルロース含量30%群で増加した。2) 小腸, 盲腸の大きさはセルロース摂取の影響を受けなかった。3) 大腸 (結腸+直腸) の長さ, 重量はセルロース含量に伴い増加し, とくに20%と30%群で有意であった。4) 滞腸時間および糞水分含量はセルロース含量に伴って減少した。

The blood pressure of spontaneously hypertensive rats (SHR) were significantly reduced by Maitake feeding for 8 weeks period beginning at a time when the animals were 10 weeks of age with well-established high blood pressure. There was no difference in the plasma total and free cholesterol, triglyceride and phospholipid levels between the Maitake fed animals and the control. On the other hand, Shiitake mushroom did not reduce the blood pressure, but significantly lower the plasma free cholesterol, triglyceride and phospholipid in compared with the control. The results suggest that dietary Maitake mushroom reduce the blood pressure.

The goitrogenicities of various preparations obtained from soybean were studied using rats. Thyroid weight, 131I uptake and the ratio of 131I-monoiodotyrosine to 131I-diiodotyrosine of the gland in rats fed the preparation was measured to determine the activity of these preparations. It was resulted that the group of rats receiving the curd had the most hypertrophied thyroid, the enlargement being equal to that in the group of these receiving soybean in the 8 weeks' feeding experiment. No difference on the content of iodine were found with the various diet preparations. The proteolytic digestion of soybean curd did not eliminate the goitrogenic property, thus, the goitrogen seems not to be a protein or peptide-like substance.

We have investigated the efficiency of pheophorbide-dimer (Pheo-dimer) localization into tumors and the effect of photodynamic therapy (PDT) using Pheo-dimer on mice bearing FM3A tumors as a part of our search for new photosensitizers. Pheo-dimer was synthesized by covalently joining two molecules of pyropheophorbide a (Pyro) with an arginine as a cross-link. The in vitro photodynamic inactivation of FM3A cells by Pheo-dimer was less than that by pheophorbide a (Pheo). The FM3A tumor took up Pheo-dimer gradually as well as Pheo, but the time required for localization of Pheo-dimer was faster. The time for attaining the maximum concentration of Pheo in the tumor after injection was 18-24h, while that of Pheo-dimer was 9-12h. A small amount of Pheo-dimer was degraded to monomers by breakage of its cross-link in the body.When irradiation was performed at 10h following administration of Pheo-dimer, the longer survival of mice bearing FM3A tumors was found in comparison with that obtained when Pheo was used. The utility of Pheo-dimer was thus expected in PDT.

The effects of vitamin E deficiency on pituitary-gonadal function in rats and the preventive effects of N,N'-diphenyl-p-phenylene diamine (DPPD) administration were examined by measuring levels of pituitary and plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH), serum and testicular levels of testosterone, and affinity and receptor sites of FSH and LH in the testis by radioimmunoassay, at 180 days after feeding of a vitamin E-deficient diet and DPPD-administered diet. Light and electron microscopic examinations were also performed on the pituitary gland and testis. In the vitamin E-deficient rats, serum and liver alpha-tocopherol concentrations decreased significantly and erythrocyte hemolytic rate and serum and tissue malondialdehyde levels increased significantly. However, the increase of hemolytic rate and malondialdehyde concentration in the vitamin E-deficient rats was somewhat lessened by the administration of DPPD. In the vitamin E-deficient rats, the gonadotropic cells in the pituitary gland manifested accelerated secretory function indicated by enlargement of cells, development of Golgi apparatus and accumulation of secretory granules, while FSH and LH concentrations in the pituitary and serum were not affected by vitamin E deficiency. However, the testosterone concentrations in the plasma and testis were significantly lower in the vitamin E-deficient rats. The decrease of testosterone in plasma and tissue was prevented by the administration of DPPD, while the degeneration of seminiferous tubules was not completely restored by DPPD. It is concluded that DPPD can compensate to some degree for the lack of antioxidative activity due to vitamin E deficiency.

Previous data have shown that the life span of small intestine epithelial cells in germ-free (GF) mice was 4.3 days, while that in conventional (CV) mice was 2.1 days, under ad libitum feeding. On the other hand, in the author's laboratory, it was also found that feeding conditions affected the cells' life span. That is, in CV mice the life span of the cells lengthened under restricted feeding (2.6 days), compared with under and libitum feeding (1.8 days). In the present experiment the life span of small intestine epithelial cells was investigated using radioautography, under controlled feeding (setting it equal to ad libitum feeding) and restricted feeding, in both CV and GF mice. Small intestine samples were taken from the middle part of duodenum, jejunum and ileum. Body weight changes, organ wet weights and intestine were also measured. In the lower part of the small intestine the effects of a restricted diet on epithelial cell life span prolongation appeared clearly in CV mice, but this effect was reduced in GF mice. This may be partly because the restricted group had slightly shorter villi in the case of GF mice.

紅こうじ菌が産生する色素の一種, モナスロルブリンが, 紅こうじ菌の一種Monascus anka UN 202-13菌に対して, どのような栄養生理的意義を有するかを検討する目的で実験を行なった。結果として, リン酸1アンモニウム0.01mol/dl, 酸性リン酸カリウム0.1g/dl, 硫酸マグネシウム0.05g/dlおよび99.5%エタノール3ml/dlを加えた培地に, モナスコルブリンを微量添加してUN 202-13菌を培養すると, 生育および色素生産量が顕著に増加することを認めた。0.005g/dlのモナスコルブリンを添加した場合, 無添加のおよそ3.5倍の生育を示し, 6倍の色素生産量の増加を認めた。これをグルコース10g/dlの場合と比較した場合, モナスコルブリン添加のほうが勝っていた。0.04g/dlのモナスコルブリンを添加した場合は, 無添加に比して, 生育はおよそ6倍, 色素生産量は8倍増加し, グルコース10g/dl添加の培地との比較では, 生育ではおよそ2倍, 色素生産量では6倍増加することを認めた。この現象は, UN 202-13菌がモナスコルブリンを単に排泄物として産生するのではなく, エタノールを有効利用するための賦活剤としての効果を有しているものと考えられ, モナスカス菌の生体内におけるなんらかの代謝に関与しているものと推察される。

The amount of voluntary exercise during pregnancy and lactation and its effect on the lactational performance in mice were investigated. Female mice were housed in exercise cages with treadwheels during periods of growth, pregnancy and lactation and the amounts of exercise were measured. It was observed that growing female mice exercised voluntarily at a level of approximately 5,000 rotations (diameter of treadwheel; 13.5 cm) per day during the 4-week growth period. After conception, the amount of exercise gradually decreased and in late pregnancy running activity decreased markedly. Throughout the lactational period dams exercised lightly. As indices of lactational performance, the body weights of pups nursed in litters of 8, milk yield and cellular development of abdominal-inguinal mammary glands were examined. There were no significant differences in the final body weights of pups, milk yield per day or development of mammary glands between exercise and non-exercise groups.

To study the effect of Shiitake (Lentinus edodes) and Maitake (Grifola frondosa) on hypertension, spontaneously hypertensive rats (SHR) were fed a diet containing 5% mushroom powder and 0.5% NaCl solution as drinking water for 9 weeks. The dietary mushrooms decreased the blood pressure. The plasma free cholesterol level decreased in Shiitake-fed animals, whereas in Maitake-fed animals the total cholesterol level decreased. There was no difference in the plasma triglyceride and phospholipid levels among the experimental groups. Shiitake feeding resulted in a decrease in VLDL- and HDL-cholesterol whereas Maitake feeding caused a decrease in VLDL-cholesterol only. Plasma LDL-cholesterol was not affected by dietary mushrooms. The results suggest that dietary mushrooms prevent blood pressure increase in hypertension.

Serum vitamin E and cholesterol levels were determined for the residents in rural regions of Yamagata Prefecture, Japan. The average serum vitamin E were 0.99 +/- 0.25 mg/100ml in 166 men, and 1.06 +/- 0.26 mg/100ml in 178 women. Only 0.6% of the subjects were below 0.5 mg/100 ml. There was a significant difference between the serum vitamin E levels of men and women. However there were no statistically significant differences among serum vitamin E of various age groups. The best correlation for serum vitamin E was found with serum cholesterol.

Hepatic and diaphragmatic hexokinase (HK) activities increased in fetuses of rats developed under maternal hyperglycemic conditions, compared to those in normal controls. In those organs, Type I and Type II hexokinase isozymes were detected by electrophoresis and densitometry with a chromatoscanner. Densitometric peak that corresponded to hepatic and diaphragmatic Type II hexokinase was also increased in the fetuses developed under hyperglycemia, compared to that of normal fetuses. These findings suggest that in the fetal liver, where significant activity of Type IV was absent, activity of Type II hexokinase varied depending on physiological state such as maternal hyperglycemia.

Lecithin-cholesterol acyltransferase was purified from rat plasma and the properties of this enzyme during the purification procedures and those of the purified enzyme were investigated in comparison with the human enzyme. The rat enzyme was not adsorbed on hydroxyapatite, which was employed for the purification of the human enzyme. When purified human enzyme was incubated at 37 degrees C in 0.1 mM phosphate buffer (pH 7.4; ionic strength, 0.00025), no alteration of enzyme activity was observed for up to 6 h. In the case of the rat enzyme, however, approximately 40% of the enzyme activity was lost under the same conditions. The human enzyme and rat enzyme were both retained on a Sepharose 4B column to which HDL3 was covalently linked, in 39 mM phosphate buffer, pH 7.4. Although the human enzyme was eluted from the column in 1 mM phosphate buffer, the rat enzyme was dissociated from the column at a lower buffer concentration (0.1 mM phosphate buffer). These findings indicate that the rat enzyme effectively associated with HDL3 in 39 mM phosphate buffer, pH 7.4, but the association was more sensitive to increase of ionic strength compared with that of the human enzyme.

野沢菜漬物中に含まれるヘオホーバイドによるラットの光過敏症の成立とそのメカニズム解明のため, 今回はヘオホーバイドのケイ光性を利用し, ラットの体内分布を観察した。その結果, 網内系細胞の多い大網膜, 脾臓への取り込みが顕著であった。また, 多少, 心臓, 肝臓への取り込みも見られたが, それほど大きなものではなかった。さらに, 光過敏症によってラットの臓器 (脳, 胸腺, 肺臓, 心臓, 肝臓, 副腎, 腎臓, 脾臓, 胃, 腸, 子宮, 膀胱, 筋肉, 背の皮膚) が組織学的にどのような変化を受けているのかを観察するため光学顕微鏡をつかって検討した結果, 脾臓において, とくに著しい変化が認められた。リンパ濾胞のくずれ, 細胞の崩壊が顕著であること, また, この崩壊細胞は濾胞内 (白髄) および赤髄内の網内系細胞で貪食されている。さらに, 赤血球とヘオホーバイドも貪食されている所見が観察された。このような組織学的変化と, すでに発表した循環器系を中心とした病態生理学的現象を関連させて考えると, 光過敏症のメカニズムは以下のとおりであろうと推定される。すなわち, ヘオホーバイドはまず, 組織学的にみて, 脂肪細胞の多い大網膜に取り込まれ, リンパ管に吸収され, 血管内にはいり全身を循環する。そして体表面に分布する毛細血管通過の際, 光照射を受け光増感反応をおこし, ヘオホーバイドが赤血球毒となり赤血球膜の脆弱化, すなわち溶血をおこし, 赤血球の内容物, とくにカリウムの漏出をきたし, このカリウムが心筋に作用し, 心臓の刺激伝導系傷害をおこしたものと考えられる。

紅麹菌が産出する色素のうち, 黄色のankaflavinの構造が種々の機器を使用することによって決定できた。また, 赤色の色素に関しては推定構造ではあるがmonascamine類似物質であろうと結論できた。 なお, この類似物質が光に対してきわめて不安定であることから, 抗酸化力のあるビタミンC, ビタミンE, メラノイジンを添加することによって, その光分解がどの程度抑制されるかを検討した。 その結果, ビタミンC添加系のほうが無添加系の約3倍の光分解抑制効果があった。以上の結果より, 光分解抑制にはビタミンCを添加することが望ましいと思われる。

The effects of diabetes on the vitamin A metabolism were studied. The concentrations of plasma retinol and retinyl ester were measured in diabetic patients using high-performance liquid chromatography (HPLC). In diabetic patients, the mean level of retinyl ester was significantly elevated compared to that of normal subjects (diabetes, 68.3 +/- 42.5 IU/100 ml of plasma; study I, 87.6 +/- 64.3 IU/100 ml of plasma; study II vs. normal, 29.8 +/- 10.3 IU/100 ml of plasma). The ultracentrifugal and column chromatographic studies were carried out to examine the distribution of retinyl ester in patient's plasma. Ultracentrifugation study showed that the mean of 72.6% of retinyl ester was recovered in the lipoproteins of density higher than 1.006 and the remainder was recovered in the chylomicron (d less than 1.006). Gel filtration profiles for the separation of plasma vitamin A demonstrated that retinyl ester presented in the HDL, LDL and larger molecular size lipoprotein (suspected to be VLDL) as well as in the chylomicron.

MASAKI, K., WAKO, Y., URANO, T. and KIMURA, S. Purification of Rat Retinol-Binding Protein Using Blue Sepharose CL-6B. Tohoku J. exp. Med., 1986, 150 (3), 249-257-Studies were conducted to isolate rat plasma retinol-binding protein, the specific transport protein for vitamin A in the rat. Retinol-binding protein was isolated from rat plasma by a new simple procedure using Blue Sepharose CL-6B, and highly purified retinol-binding protein was obtained. This procedure included DEAE-cellulose chromatography at pH 6.0, Sephadex G-75 gel filtration in the presence of 3.0M urea, Blue Sepharose CL-6B affinity chromatography at pH 7.0 and finally Sephadex G-100 gel filtration at pH 7.4. The third step completely accomplished the dissociation and separation of retinon-binding protein from its complex with prealbumin and plasma albumin. This procedure is a significant improvement over previously published procedures, in which sample recycling and preparative polyacrylamide gel electrophoresis are necessary. The molecular weight, electrophoresic behaviour, ultraviolet and fluorescence spectra of the retinol-binding protein were similar to those appearing in other reports.

Histopathological changes in spontaneously hypertensive rats were studied after the animals had been fed Shiitake (Lentinus edodes) and Maitake (Grifola frondosa) mushroom powder diets, with 0.5% NaCl solution as drinking water for 9 weeks. Histological changes in control and Shiitake-fed rats were essentially the same, consisting of necrosis of the medial smooth muscle cells, vacuolization in the media of the aorta, fatty liver development, maceration in the myocardial muscle cells and vacuolization in the myocardium. In Maitake-fed animals large amounts of glycogen were observed in the liver, but the animals were otherwise normal in all respects. Dietary Maitake seems to play an important role in preventing the histological degenerative changes in SHR and thus may imply some benefits to be gained through blood pressure reduction and an improvement of lipid metabolism.

[48V]vanadyl-pheophorbide (48V-Pheo) was synthesized by insertion of 48V into pheophorbide (Pheo), a decomposition product from chlorophyll. At 24 h after injection, 48V-Pheo showed a clearer image of an FM3A tumor than inorganic 48V. This agent also accumulated in MH 134 and S 180 tumors as well as in FM3A tumors. The imaging efficiency was dependent on the affinity of Pheo for tumors.48V-Pheo seems to be suitable as a tumor imaging agent in conjunction with photodynamic therapy.

Adsorption of vitamin B12, with and without gastric mucosa extract (GME), to intestinal mucosa homogenates from rats was studied at various stages of growth. The development of the activities of producing gastric HCl and pepsinogen was also investigated. The intestine from newborn animals showed extremely high adsorption of vitamin B12 in the absence of GME. The GME-independent vitamin B12 adsorption fell rapidly with time, approaching adult level at about 20 days of age. Stimulation of vitamin B12 adsorption by adult GME and the gastric HCl secretion reached adult levels at about 20 days. On the other hand, intrinsic factor formation and pepsinogen formation did not reach adult levels until about 30 days. Histologic investigations of the gastric gland and ileal villus agreed with the above-mentioned experimental results. The intrinsic factor-dependent vitamin B12 absorption became a predominant system at about 30 days after birth.

Hourly changes of 131I uptake and the changes in several indices of thyroid at different time intervals after beginning of an iodine deficient diet with or without propylthiouracil were determined. An amino acid mixture was used as the protein source in the present experiments. The magnitude of iodine uptake and the ratio of monoiodotyrosine to diiodotyrosine increased according to the length of time on low iodine diet. The earlier appearance and more enlargement of peak of the ratio of monoiodotyrosine to diiodotyrosine in rats treated with small dose of propylthiouracil than in those untreated suggested that propylthiouracil might also bring about the lack of iodine by inhibiting the iodination at substrate level.

白ネズミの皮膚と尾腱を用い, コラーゲンの加齢および, A欠乏時の変化を, コラーゲンの熱収縮を指標にして検討した。1) コラーゲンの熱収縮温度は年齢にかかわらず水溶液中で60～65℃であった。2) 加齢, およびA欠乏により, 白ネズミの皮膚と尾腱の総ヒドロキシプロリンの量は増加した。3) 脱脂皮膚と尾腱を65℃, 10分間, 水中で加温した場合, 外液に遊出してくる遊離型ヒドロキシプロリンと結合型ヒドロキシプロリンの量は, 加齢にともなって有意の減少を示した。4) 同様の実験をA欠乏白ネズミの皮膚で試みたところ, 欠乏群は対照群にくらべて, 遊離型ヒドロキシプロリンは増加する傾向を示したが, 結合型ヒドロキシプロリンは有意に減少した。

1. Analogues of pantothenic acid, i.e., ω-methyl pantothenic acid, pantoyltaurine, ω-methyl pantoyltaurine and analogues of pantethine i.e., ω-methyl pantethine, bis (N-pantoyl-β-aminoethyl) disulfide, bis (N-methyl pantoyl-β-aminoethyl) disulfide, were synthesized and the inhibitory effects of these analogues on lactic acid bacteria were examined and inhibition indexes were calculated.2. Inhibitory effects of these analogues on germination of higher plants, i.e., “yukina” and barley, were also studied. It was observed that the analogues inhibited the germination and growth of the higher plants, and the inhibitory actions were considerably reversed by the presence of an additional equimolecular amount of pantothenic acid (PaA). Furthermore, the existence of antagoism between pantoic acid, a PaA precursor, and its analogue in the germination of higher plants was shown.3. The possibility to induce a nutritional deficiency in the chick embryo by injecting PaA analogue, ω-methyl PaA, was found. A lethal dose of ω-methyl PaA on the second day of incubation was 10.0mg per egg and this inhibitory effects were remarkably prevented by a simultaneous injection of PaA. Interference ratio (analogue: vitamin) was roughly 200:1.4. In the animal experiment, the weight gain of the male DD-strain mice diminished proportionately with the level of supplemented ω-methyl PaA. The inhibitory effects were prevented by a simultaneous addition of PaA. “Interference ratio” was found to be 100:1 to 60:1. Deficiency syndromes induced by ω-methyl PaA were observed.5. Effects of PaA analogue and pantetheine analogues on the acetylation of sulfanilamide in pigeon liver homogenate were studied. A PaA analogue, ω-methyl PaA, was inert for acetylation, but a pantetheine analogue, ω-methyl pantethine, showed a remarkable inhibition.6. Effects of these analogues were discussed and the mechanism of their interference action were also discussed.

For the purpose of elucidating the physiological significance of intrinsic factor (IF) in vitamin B12 absorption, comparative studies on the adsorption of vitamin B12 to intestinal mucosa homogenate of unweaned (aged 48 hours old) and adult rats were carried out. Any material having IF activity on the intestine of the adult rat and the unweaned rat was not secreted from the stomach of the unweaned rat. This result was confirmed by the histologic findings that the chief cells of the unweaned rat, when examined on the fundus portion of the stomach, were still undeveloped. The adsorption of vitamin B12 to the intestinal mucosa homogenate of the unweaned rat seemed to be independent on the IF and the presence of Ca++ ion. The amount of vitamin B12 adsorbed to intestinal mucosa homogenate of the unweaned rat, as expressed by mg vitamin B12/kg body weight, was from 4 to 10 times larger than that of the adult rat. The high capacity of the intestinal mucosa homogenate of the unweaned rat to adsorb vitamin B12, regarded as the first step of vitamin B12 absorption, may be related to the fact that unweaned rat can absorb a large amount of vitamin B12. The small intestine of the unweaned rat appears to take indiscriminately fairly large molecules. The results of the experiments which investigated the effects of bivalent cations on the adsorption of vitamin B12 to intestinal mucosa homogenate suggested that the so-called sequential uptake might have occurred.

加令および, ビタミンA欠乏によるシロネズミ皮膚ムコ多糖類の変化について実験を行ない次の結果を得た。(1) 脱脂皮膚固型成分は, 3カ月から6カ月にかけて増加がみられたが, その後は減少の傾向が認められた。(2) 脱脂皮膚中の総ムコ多糖類の含量は, 3カ月から6カ月にかけて増加が認められたが, 6カ月以後では変化はみられなかった。一方, ビタミンA欠乏は, この変化に影響をおよぼさなかった。(3) ムコ多糖類の各成分において, ヒアルロン酸, ヘパリチン硫酸は加令にともなって増加する傾向がみられたが, コンドロイチン硫酸, ヘパリンは逆に減少するこのが認められた。(4) ビタミンA欠乏は, ヘパリンを除いて, 加令による変化と同じような変化をおよぼすことが認められた。(5) 加令によるムコ多糖類の変化は, 老化時期よりも成熟期までにみられることが明らかになった。

白ネズミの皮膚と尾腱を用い, 加齢, ならびにA欠乏におけるコラーゲンの変化を観察した。1) 酸可溶コラーゲンは加齢にともなつて減少し, 酸不溶コラーゲンは増加してくる。2) A欠乏白ネズミにおいては, 欠乏群では対照群にくらべて酸可溶コラーゲンの全コラーゲンに占める割合が小さく, 酸不溶コラーゲンはこの逆であった。3) 加齢にともない結合組織の繊維化が促進されることを観察した。4) A欠乏は加齢と同様に結合組織の繊維化を促進することを観察した。

1日1回, 2時間だけ摂食するように訓練した白ネズミを用いて, 無たん白食に切り替えたときの血中遊離アミノ酸, 肝臓遊離アミノ酸, 肝臓たん白などめ変化を, 20%カゼインで飼育した対照群と比較検討し, 以下の結果を得た。1) 血中遊離アミノ酸は, 対照では摂食により上昇したのに対し, 無たん白群では摂食後24時間まで変化はなく一定のレベルに保たれた。2) 肝臓遊離アミノ酸の変化は両群で4時間までは異なって, 対照群では一定に保たれたのに対し, 無たん自群では低下した。その後の変動は両群で類似していたが, 無たん自群では対照より常に低いレベルにとどまった。3) 肝臓たん白, RNAの変動は4時間以後, 無たん白群が対照にくらべて低く, 24時間後には対照の80%になった。4) meal-feedingを用いた飼料の切替えによって, 無たん白食投与後4時間で, その影響が現われることが明らかにされた。しかし血中遊離アミノ酸プール, 肝臓アミノ酸プール, 体内易動性たん白の変動といった一連の系で変動のつながりは明らかではなかった。

1. The growth-promoting effect of ω-methyl pantothenic acid on Saccharomyces sake (strain No. 6) was studied and it was found that pantothenic acid can be replaced with β-alanine in Saccharomyces sake as in other yeasts. ω-Methyl pantoic acid, formed by the removal of β-alanine from ω-methyl pantothenic acid, has a slight inhibitory effect but it has a remarkable growth-promoting effect after addition of an equimolar amount of β-alanine. It supports the hypothesis that the β-alanine moiety contained in ω-methyl pantothenic acid can be reutilized for the biosynthesis of pantothenic acid in this yeast.2. Biological activities of pantothenic acid analogues other than ω-methyl pantothenic acid on Saccharomyces sake were also studied. Bis(N-pantoyl-β-amino ethyl) disulfide and bis(N-methyl pantoyl-β-amino ethyl) disulfide were found to have an inhibitory effect. These analogues do not contain the β-alanine moiety in the molecules. Panthenol, which was formed by the replacement of the β-alanine moiety in pantothenic acid with ethanolamine, gave no effect on the growth of the yeast. These results support the possibility that the growth-promoting effect of ω-methyl pantothenic acid is due to the β-alanine moiety contained in the molecule.3. Though ω-methyl pantethine contains a β-alaine moiety in the molecule, it showed an inhibitory effect on the yeast. It was also shown that pantethine can not replace pantothenic acid and that bis (N-β-alanyl-2-amino ethyl) disulfide, a moiety of pantethine or ω-methyl pantethine molecules, had only a slight promoting effect. β-Alanine contained in these molecules of the pantethine level cannot be utilized effectively. The reason is still unknown, but it seemed probable that it is related not only with the permeability of the cell membrane but also with the enzymatic system in the pathway of coenzyme A biosynthesis.4. Biological activities of pantothenic acid and pantethine were also studied. The growth-promoting effect of pantothenic acid on Lactobacillus arabinosus 17-5 and Leuconostoc mesenteroides P-60 were found to be greater than that of pantethine. Lactobacillus arabinosus 17-5 showed exceptionally high specificity. On the other hand, pantethine was more effective than pantothenic acid on Lactobacillus helveticus IAM-1042 and Lactobacillus bulgaricus B1. However, the growth of these bacteria in this basal medium was very poor, but the growth was improved by the addition of skim milk, so that it seemed likely that the medium is devoid of some nutrional factors necessary for these bacteria.

Dependency of superoxide anion () generation on protein kinase C (PKC) or calmodulin (CaM) in macrophages (MPs) was investigated using a -specific chemiluminescence probe with the Cypridina luciferin analog 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[l,2-a]-pyrazin-3-one (MCLA). In opsonized zymosan (OZ)-stimulated MPs, 40% of the MCLA-dependent chemi-luminescence disappeared when the PKC inhibitor l-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) or the CaM antagonist N-(6-aminohexyl)-5-chloro-l-naphthalenesulfon-amide (W-7) was added. In MPs stimulated by 12-o-tetra-decanoylphorbol-13-acetate (TPA), addition of H-7 strikingly lowered MCLA-dependent chemiluminescence, but W-7 had only a little effect. These results indicate that both PKC and CaM are involved in OZ-stimulated generation in MPs and that TPA-stimulated generation depends not on CaM but on PKC.

(1) シロネズミを運動または絶食させて体内エネルギー代謝を活発にさせたときの肝臓, 心臓および骨格筋の総カルニチン量の変動を検討した。(2) シロネズミに1時間の遊泳運動を負荷した場合, 肝臓で総カルニチン含量が減少し, 心臓と腓腹筋で有意に増加した。(3) 1時間遊泳運動を30分の休息を2回はさんで3回, 計3時間運動を負荷して疲労させた場合, 肝臓のカルニチン量は対照と同レベルに回復したが, 心臓では対照より有意に減少した。しかし, 腓腹筋では1時間遊泳運動動物と同じ高いレベルを維持した。(4) 5日間の絶食により, 心臓と腓腹筋では総カルニチンの有意な増加が認められ, とくに腓腹筋で著しかった。しかし肝臓は有意な変動は認められなかった。

The distribution of vitamin E in human serum lipoprotein fraction was investigated by measuring the amount of vitamin E in various protein fractions prepared by ultracentrifugation, gel filtration and electrophoresis. The larger part of the total serum vitamin E (up to 44%) was present in the alpha1-lipoproteins, while the beta-lipoproteins contained smaller concentrations (up to 26%).

Conventional (CV) and germ-free (GF) mice were fed on a semi-synthetic diet containing graded levels of cellulose (0, 5, 15 and 30%), and thereafter the length and wet weight of intestine, the morphology of mid-jejunum epithelium and the turnover of mid-jejunum epithelial cells were determined. The following results were obtained. enlarged stomachs were observed in CV mice fed on a non-cellulose or 30% cellulose diet, but there were no differences found among the four dietary groups in GF mice. On the other hand, no effect of intestinal bacteria was observed, at least with regard to caecum weight, since the responses of caecum wet weight to the graded cellulose intake in CV mice were similar to those in GF mice. The responses of intestine length to graded cellulose intake differed between CV and GF mice, indicating that intestinal bacteria may modify the length of intestine in some way. Marked differences were observed in the responses of villus length to graded levels of cellulose between CV and GF mice. That is, in CV mice there was a gradual increase in villus length as cellulose content increased, whereas in GF mice there was a marked decrease in villus length. In the CV mice, graded levels of dietary cellulose had no effect on the epithelial cell turnover. On the other hand, in the GF mice it was observed that the greater the amount of dietary cellulose, the faster the turnover rate becomes. As a result, dietary cellulose would enhance the turnover rates of jejunal epithelial cells only in the absence of intestinal bacteria.