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Biomedical subjects

K Nakata

Publications and source records attributed to K Nakata.

At least 469 records · Page 26Linked to original sources
PubMed1987

[Damaging action of human recombinant TNF on tumor vessels as an aspect of its anti-neoplastic action against Meth A sarcoma in mice].

Effect of human recombinant TNF (rHu-TNF) on tumor blood vessels was investigated in relation to its mode of anti-neoplastic action against Meth A sarcoma in BALB/c mice. The extent of the blood vessel lesion was evaluated by measuring the degrees of blueing and hemorrhage after intravenous injection of Evan's blue. When injected intravenously into mice bearing Meth A cells in the abdominal skin transplanted 8 days previously, rHu-TNF, at doses of 3000 and 10,000 units/mouse produced dose-related lesioning of blood vessels in the sarcoma and the adjacent skin but not in the skin distant from the sarcoma. Similar lesioning of blood vessels in the adjacent skin was seen after intravenous administration of 10,000 units/mouse of rHu-TNF in mice with the sarcoma in which the cells had been selectively killed by intratumoral injection of acetic acid (20%, 0.01 ml). On the other hand, rHu-TNF (10,000 units/mouse, i.v.) produced weak lesioning of blood vessels in the granuloma tissue caused by subcutaneous implantation of felt pellets and in the adjacent skin but not in the operation wound in mice with the sarcoma. These results suggest that rHu-TNF damages newly formed blood vessels, particularly those connected with the sarcoma, without influencing blood vessels in normal skin and healing wounds in mice with Meth A sarcoma.

Animals↗
PubMed1986

Effects of sodium loading on antihypertensive responses to an angiotensin-converting enzyme inhibitor in spontaneously hypertensive and renal hypertensive rats.

Sodium loading significantly attenuated the antihypertensive potency of an angiotensin-converting enzyme inhibitor, SA446, in 2-kidney, 1-clip renal hypertensive rats, but the potency of SA446 remained unchanged in spontaneously hypertensive rats. Basal levels of plasma renin activity of both types of hypertensive rats were suppressed by sodium loading. From these results, it appeared that a different mechanism was involved in the maintenance of hypertension in 2-kidney, 1-clip renal hypertensive rats and in spontaneously hypertensive rats. It also appeared that the mechanism of the antihypertensive action of angiotensin-converting enzyme inhibitors was not explainable only by the suppression of the plasma renin-angiotensin system.

3-Mercaptopropionic Acid↗
PubMed1986

ECoG sleep-waking rhythms and bodily activity in the cerveau isolé rat.

In rats with a high mesencephalic transection, isolating both the locus coeruleus and raphe nuclei from the forebrain, Electrocorticogram (ECoG) and Electromyogram (EMG) of the neck muscles were continuously recorded. Normal sleep-waking ECoG changes with a significant circadian rhythm reappeared in 4 to 9 days after transection. Neck muscle EMG and bodily movements were independent of the ECoG changes and did not show any significant circadian rhythm. In these high mesencephalic rats with sleep-waking ECoG changes, large bilateral hypothalamic lesions were made by passing DC current either in the preoptic area or in the posterior hypothalamus. After the preoptic area lesions the amount of low voltage fast ECoG per day markedly increased, whereas after the posterior hypothalamic lesions, the total amount of low voltate fast wave per day decreased showing long-lasting slow wave sleep pattern. These results support an idea that the forebrain, especially in the hypothalamus including the preoptic area, a mechanism inducing sleep-waking ECoG changes is localized.

Animals↗
PubMed1986

Recombinant human tumor necrosis factor--II. Antitumor effect on murine and human tumors transplanted in mice.

Recombinant human tumor necrosis factor (rHu-TNF) was found to exhibit potent antitumor activities not only against murine tumors, i.e. Meth A sarcoma, B 16 melanoma, colon 26 adenocarcinoma, Lewis lung carcinoma and MH134 hepatoma, transplanted in syngeneic mice but also against human tumors, i.e. HMV-2 melanoma, PC-10 lung carcinoma and GOTO neuroblastoma, heterotransplanted in nude mice. rHu-TNF caused necrosis of all tumors tested and inhibited their growth in a dose dependent manner. Complete regression of tumors was observed in mice bearing Meth A, B16, colon 26, MH134, HMV-2 and PC-10 but not in mice bearing Lewis lung carcinoma and GOTO neuroblastoma. The prolongation of survival time was also observed in syngeneic mice transplanted with murine tumors except Lewis lung carcinoma. The antitumor effect of rHu-TNF was more evident when it was given intratumorally than when given intravenously. The feasibility of rHu-TNF as a drug for cancer therapy is discussed.

Adenocarcinoma↗
PubMed1986

[Antihypertensive effects of SA446, hydralazine and the combination on renal hypertensive rats and spontaneously hypertensive rats by long-term treatment].

SA446 [(2R, 4R)-2-(o-hydroxyphenyl)-3-(3-mercaptopropionyl)-4- thiazolidinecarboxylic acid] (30 mg/kg/day), an orally active angiotensin-converting enzyme inhibitor, lowered significantly indirect systolic blood pressure (SBP) of 2-kidney, 1-clip renal hypertensive rats (RHR) by consecutive oral administration over a 14 week period. Daily oral dosing of hydralazine (2 mg/kg/day) for 14 weeks had little or no effect on SBP, but potentiated the antihypertensive effect of SA446. One to two weeks after discontinuation of the drugs, SBP in SA446 and the combination groups returned to the control level. Survival rates were 64%, 30% in the control and hydralazine group, respectively, but no death was observed in the SA446 group and the combination group throughout the administration period. Twenty-four hour urine volume and water intake tended to increase in the hydralazine group through the administration period, but increased apparently in the SA446 group and the combination group after discontinuation of the drugs. Daily oral dosing of SA446 (45 mg/kg/day) for over 16 weeks completely prevented the development of hypertension in spontaneously hypertensive rats (SHR). Daily oral dosing of hydralazine (2 mg/kg/day) similarly prevented the development. The combined effect with SA446 and hydralazine on the development was also observed. SBP in the SA446 group and the combination group increased gradually after discontinuation of the drugs, but were maintained at a low level as compared with the control group 3 weeks after discontinuation, while hydralazine gave a rapid return. No influences were observed in 24 hr-urine volume and water intake during and after the administration period in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Mercaptopropionic Acid↗
PubMed1986

[Combined effect of (2R, 4R)-2-(o-hydroxyphenyl)-3-(3-mercaptopropionyl)-4-thiazolidinecarbo xyl ic acid (SA446) with hydrochlorothiazide or propranolol on development of hypertension in spontaneously hypertensive rats (SHR) by long-term administration].

Effect of long-term oral administration of the converting enzyme inhibitor (2R, 4R)-2-(o-hydroxyphenyl)-3-(mercaptopropionyl)-4-thiazolidinecarboxylic acid (SA446) in combination with hydrochlorothiazide or propranolol on the development of hypertension was examined in spontaneously hypertensive rats (SHR). The development of hypertension in SHR was markedly suppressed by the treatment with SA446 (45 mg/kg, p.o.) for 17 weeks from 8 weeks of age, the pre-stage of hypertension. Long-term administration of hydrochlorothiazide (20 mg/kg, p.o.) also showed an obvious antihypertensive effect, but the effect was less potent than that of SA446. On the other hand, propranolol (20 mg/kg, p.o.) showed a slight or little antihypertensive effect. The combined administration of hydrochlorothiazide and SA446 produced a more potent antihypertensive effect than the administration of SA446 alone. On the other hand, the combined use of propranolol had no influence on the antihypertensive effect of SA446 by long-term administration in SHR. Plasma renin activities measured after 17 weeks treatment of the drugs indicated that the renin-angiotensin system was activated by hydrochlorothiazide. These results suggest that the antihypertensive effect of long-term administration of SA446 in SHR is enhanced by the combined administration of diuretics such as hydrochlorothiazide, which activates the renin-angiotensin system.

3-Mercaptopropionic Acid↗
PubMed1986

Species difference of (2R,4R)-2-(o-hydroxyphenyl)-3-(3-mercaptopropionyl)-4-thiazolidinec arb oxylic acid (SA446) in inhibition of angiotensin converting enzyme.

A marked species difference was observed both in vitro and in vivo in the activity of SA446, an orally active inhibitor of angiotensin converting enzyme (ACE), as compared with that of captopril in five different animal species. The activity of SA446 in vitro in inhibiting plasma ACE correlated with the activity in vivo as determined by inhibition of the pressor response to angiotensin I (AI). SA446 was more potent as an inhibitor of AI response in dogs, cats and rabbits than in guinea pigs and rats. Furthermore, ACE activity in whole blood in vivo was inhibited by SA446, and the activity of SA446 was also more potent in dogs than in rats. The concentration of SA446 in the ultrafiltrate of blood (free form) was significantly higher in dogs than in rats, while no difference was observed in level of SA446 in the whole blood (free and protein-bound form) between these two species after intravenous injection. The binding rate of SA446 to plasma protein of rats in vitro was more than twice as high as that of dogs. These results suggest that the difference in the protein binding rate of SA446 is reflected in ultrafiltrate level and is one of the important components in defining the species difference in SA446 action.

3-Mercaptopropionic Acid↗
PubMed1986

Effect of intrahepatic arterial infusion of 131I-labelled lipiodol on hepatocellular carcinoma of rat.

Intrahepatic arterial infusion of 131I-labelled lipiodol was performed to study the intrahepatic distribution of lipiodol and to determine the radiation effect on 3'-Methyl-4-Dimethylaminobenzene (DAB) induced hepatocellular carcinoma (HCC) in rats. From the findings of the softex films and scintigrams of the liver, according to the time course, lipiodol was found to accumulate in the tumour tissues parallel with the degree of perfusion, and it remained in the tumour tissues for an extended period probably due to the delay of the degradation of lipiodol compared to that in non tumour tissues. It was noticed that the lipiodol, accumulated and deposited selectively in the tumour tissues, existed mostly in the extracellular space but not in the intracellular space. In histological studies of the resected specimens of the tumours, complete necrosis of hepatocellular carcinoma was recognized 2 to 8 weeks after the infusion of 131I-labelled lipiodol, while there was none in the control group where cold lipiodol was employed. These results suggest that the most effect on hepatocellular carcinoma in this study is caused by the radiation effect of 131I-labelled lipiodol.

Animals↗
PubMed1986

Antitumor effect of recombinant human interleukin 1 alpha against murine syngeneic tumors.

Interleukin 1 (IL1) has been suggested to have antitumor activity but there is no clear-cut evidence of an in vivo antitumor effect of pure IL1. In this work, the antitumor effect of purified recombinant human IL1 alpha (rHu-IL1 alpha) was assessed on murine tumors transplanted intradermally in syngeneic female mice. rHu-IL1 alpha inhibited the growth of Meth A sarcoma in BALB/c mice, B16 melanoma in C57BL/6 mice and colon 26 adenocarcinoma in CDF1 mice, as well as the spontaneous pulmonary metastasis of Lewis lung carcinoma in BDF1 mice, at intratumoral (itu), intramuscular (im), and/or intravenous (iv) doses ranging from 1 to 30 micrograms/mouse. The antitumor effect of rHu-IL1 alpha was generally dose- and route-dependent, being highest by the itu route, followed by the im and iv routes in that order. Palpable 7-day-old Meth A sarcoma was completely regressed in some mice given rHu-IL1 alpha itu once at doses of 10-30 micrograms/mouse (cured ratio; 71-100%), once a day for 3 days at doses of 3-30 micrograms/mouse (57-86%) or once a day for 7 days at doses of 1-10 micrograms/mouse (14-100%). Palpable 7-day-old B16 melanoma was also regressed completely in some mice given seven itu doses of 10-30 micrograms/mouse (14-86%). One-day-old Meth A sarcoma was more sensitive to rHu-IL1 alpha than 7-day-old Meth A sarcoma. There was no macroscopic sign of inflammation at the site of injection of rHu-IL1 alpha. These results show that rHu-IL1 alpha has antitumor activity in vivo and is worthy of further study as a potential antitumor agent.

Adenocarcinoma↗
PubMed1986

[Combined effect of PT-050 (recombinant human TNF) and antitumor drugs on syngeneic murine tumors].

The combined effect of PT-050 (recombinant human TNF) and various antitumor drugs was investigated using murine colon 26 adenocarcinoma, Meth A sarcoma and B16 melanoma transplanted into syngeneic mice. When colon 26- or Meth A- bearing mice were intravenously given PT-050 in combination with mitomycin C (MMC), doxorubicin (DXR), cis-platinum (CDDP), 5-fluorouracil (5-FU) or cyclophosphamide (CPA), a significant synergistic effect was observed, that is, both the inhibition rate of tumor growth and the cured ratio were increased significantly when compared with those given each drug alone. Similarly, an augmentation of the antitumor effect was also observed in B16-bearing mice by a combined treatment with PT-050 and these antitumor drugs. These results suggest that the combination chemotherapy of PT-050 with various antitumor drugs may be useful for cancer therapy.

Adenocarcinoma↗