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K Takashina

Publications and source records attributed to K Takashina.

At least 19 recordsLinked to original sources
PubMed1995

Preferential impairment of avoidance performances in amygdala-lesioned mice.

To clarify the role of the amygdala in the fulfillment of memory and/or learning, amygdala-lesioned mice were tested in passive and active avoidance performances and also in spatial learning tasks. Although the lesioned animals showed deteriorated performances in both passive and active avoidance tests, they executed the spatial learning tasks as well as the control mice. The learning deficit was prominent in the process of memory acquisition of passive and active avoidance tasks, suggesting that the amygdala might be involved in the acquisition processes of these avoidance tests. The locomotor activities of the lesioned animals were slightly increased, but there was no significant difference compared with the control mice. These findings indicate that the amygdala plays a crucial role preferentially in the avoidance learning rather than the spatial learning.

Amygdala↗
PubMed1994

Effects of DX-9386, a traditional Chinese preparation, on passive and active avoidance performances in mice.

The acute effects of DX-9386, a traditional Chinese medicinal preparation (ginseng, polygala, acorus and hoelen), were studied on learning and memory performances in passive and active avoidance tests in normal, as well as in learning-impaired, mice. A single oral administration of the prescription had no effect on memory registration, consolidation or retrieval or on motor activity in normal mice. DX-9386 reduced the ethanol-induced impairment of memory registration in the step-down test and also tended to ameliorate the scopolamine-induced memory registration deficit in the same test. The preparation reduced the number of spontaneous responses in the active avoidance test. The preparation also prolonged the disappearance of righting reflex induced by pentobarbital. These results suggest that DX-9386 ameliorates the impairment effect of ethanol on learning and memory processes and also exhibits a sedative effect.

Administration, Oral↗
PubMed1994

Prolongation of life span and improved learning in the senescence accelerated mouse produced by aged garlic extract.

The effects of aged garlic extract (AGE) on longevity and learning and memory performances were studied in the senescence accelerated mouse (SAM). A solid diet containing 2% (w/w) AGE was given to SAM from 2 months of age. The survival ratio of SAM P8, senescence accelerated animals, treated with AGE was significantly higher than that of untreated controls. AGE, however, did not affect the life span of SAM R1, a senescence-resistant strain. AGE had no effect on body weight and motor activity. In the passive and conditioned avoidance tests, AGE markably improved a memory acquisition process in the step-down and shuttle-box tests, and also a retention process in the step-through and step-down tests in SAM P8. The beneficial effects of AGE were observed in a memory retention process in the step-down test and in an acquisition stage in lever-press test in SAM R1. These results suggest the possibility that AGE might be useful for treating physiological aging and age-related memory deficits in humans.

Aging↗
PubMed1994

Anti-aging effect of DX-9386 in senescence accelerated mouse.

The effects of DX-9386, a traditional Chinese prescription (ginseng, acorus, polygala and hoelen) were studied on life span, the degree of senescence, motor activity and the antibody production response in senescence accelerated mouse (SAM). DX-9386-containing food was given to SAM for 13 consecutive months from 2 months of age. DX-9386 significantly prolonged the life span of SAM, prevented body weight decrease with aging and tended to improve the senile syndrome. The motor activity of SAMP8 was higher than that of SAMR1, and DX-9386 tended to increase the activity in SAMP8. The in vivo antibody production was markedly decreased in SAMP8 and DX-9386 showed no ameliorating effect on that. These results suggest that DX-9386 has anti-aging impact.

Aging↗
PubMed1992

Enhanced tumor localization of monoclonal antibody by treatment with kininase II inhibitor and angiotensin II.

The effect of kininase II inhibitor, enalapril, on the delivery of monoclonal antibody A7 to the targeted tumor was investigated using athymic mice bearing human colon cancer, SW1116. Enalapril alone, which enhances tumor vascular permeability through the kinin-generating cascade, did not increase the uptake of 125I-labeled A7 (125I-A7) in SW1116 due to the systemic hypotension induced by its inhibitory effect on angiotensin converting enzyme. However, with combined angiotensin II (AT-II) and enalapril treatment, a 2-fold increase in the accumulation of 125I-A7 was seen when compared to A7 alone. This marked increase was presumably due to increased tumor vascular permeability induced by enalapril combined with the absence of hypotension due to the actions of AT-II. This approach might be useful in radioimmunodetection and immunotargeting chemotherapy using monoclonal antibody.

Angiotensin II↗
PubMed1991

Chemical engineering of the monoclonal antibody A7 by polyethylene glycol for targeting cancer chemotherapy.

The murine monoclonal antibody A7 (Mab A7) against human colon cancer was chemically modified with methoxypolyethylene glycol (PEG) (Mr 5000). A high substitution of PEG molecules on Mab A7 produced a progressive reduction in antibody-binding activity. The pharmacokinetic and immunological properties of PEG-modified monoclonal antibody A7 (Mab A7) and the PEG-modified F(ab')2 fragment, which retained their antibody-binding activity, were assessed and compared with the parent Mab A7 and the parent F(ab')2 fragment. Blood clearance of PEG-modified antibodies appeared to be diminished by PEG modification and was fitted by a two-compartment model. Low PEG-substituted Mab A7 showed less organ uptake in the liver and spleen and similar uptake in the lung and kidney, compared with the parent Mab A7. PEG-F(ab')2 showed less uptake in the liver and kidney. Both preparations exhibited less tissue:blood ratios in all resected organs as compared with parent antibodies. Tumor localization was enhanced by PEG modification for the F(ab')2 fragment, but not by PEG modification for the whole Mab A7. Multiple i.v. administration of PEG-modified antibody to rabbit did not appear to elicit a measurable immune response to the antibody portion of the conjugate. In conclusion, PEG-modified antibodies are promising reagents as drug carriers to the target tumor.

Animals↗
PubMed1991

Comparative pharmacokinetic properties of murine monoclonal antibody A7 modified with neocarzinostatin, dextran and polyethylene glycol.

The murine monoclonal antibody A7 (Mab A7) was chemically modified with several macromolecules: dextran, polyethylene glycol and the anti-cancer polypeptide neocarzinostatin. The pharmacokinetic properties of the combinations were subsequently examined. Radioimmunoassay revealed that all preparations retained their antigen-binding activities. The Mab A7-neocarzinostatin conjugate was cleared from the blood circulation with a kinetic pattern almost identical to that of the parent Mab A7. Of the three preparations, Mab A7-dextran (A7-Dx) was removed the most rapidly from the circulation. Mab A7-polyethylene glycol (A7-PEG) exhibited the slowest blood clearance curve, with twice the half life of the parent Mab A7 in the circulation. In normal organ distributions, A7-Dx exhibited the highest liver, spleen and kidney uptake, and A7-PEG showed the lowest uptake, when expressed as tissue:blood ratio. Although A7-Dx exhibited lower tumor uptake, there was no significant difference among the three conjugates in tumor-bearing nude mice. A7-PEG seems to be a good candidate for targeted cancer therapy using antibody due to its high blood retention but low normal organ uptake.

Animals↗
PubMed1991

Pharmacokinetic analysis of the monoclonal antibody A7-neocarzinostatin conjugate administered to nude mice.

The pharmacokinetics of a disulfide linked conjugate of a murine monoclonal antibody A7 with neocarzinostatin (A7-NCS) was studied following its intravenous administration to nude mice. Disappearance of the conjugate from the circulation was biphasic: an early rapid phase was followed by a much slower phase. The conjugate was removed from the blood circulation with a half-life of 12 hr, showing nearly the same kinetics as the free antibody. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that the disulfide linkage in A7-NCS was stable at least for 48 hr after administration of the conjugate to nude mice. The conjugate concentration in a human colon cancer SW1116 derived tumor reached maximum at 24 hr after injection and remained high for an additional 24 hr. The passive hemagglutination inhibition assay revealed that NCS in the conjugated form can be efficiently delivered to the target tissue. The present report indicates that A7-NCS was sufficiently stable in circulation to reach the target tumor without releasing NCS.

Animals↗
PubMed1990

Polyethylene glycol modification of the monoclonal antibody A7 enhances its tumor localization.

The F(ab')2 fragment of murine monoclonal antibody A7 was covalently bonded to polyethylene glycol (PEG, molecular weight: 5000) and the conjugate was compared to the parent F(ab')2 fragment by in vitro and in vivo studies. PEG-conjugated antibody fragment retained its antigen-binding activity in a competitive radioimmunoassay. The conjugate had a longer half-life and showed increased accumulation in tumors. Although the tumor: blood ratio for parent F(ab')2 fragment was higher than that for the conjugate, it showed higher value than whole MAb A7. The tissue: blood ratios were kept low with the conjugate, indicating that the conjugate was uptaken to normal organ with lesser extent, as compared with parent F(ab')2 fragment. Our findings indicate that this PEG-conjugated F(ab')2 fragment could be a promising carrier for use in targeting cancer chemotherapy.

Animals↗
PubMed1990

Binding, internalization and the cytotoxicity of monoclonal antibody A7-neocarzinostatin conjugates (A7-NCS) in target cells.

To study the mechanism of action of the monoclonal antibody A7-neocarzinostatin conjugates (A7-NCS), the internalization of the antibody and its conjugate into target cells was examined. The incubation of radiolabeled A7 and A7-NCS with target cells revealed that both were taken up by target cells in a time dependent fashion. The immunocytochemical study using anti-NCS also revealed the intracellular localization of the conjugates. The cytotoxicity of the conjugate was markedly reduced when the binding sites were occupied by an excess of antibody on the cell surface. These results showed that A7-NCS was internalized into target cells and that its cytotoxicity was mediated through specific binding and internalization.

Animals↗
PubMed1989

Characterization of putrescine production in nongrowing Vibrio parahaemolyticus cells in response to external osmolality.

Nongrowing Vibrio parahaemolyticus cells rapidly produced putrescine (Put) from added arginine when subjected to a low osmotic stress. This phenomenon was characterized in connection with a regulatory mechanism of the responsible enzymes, arginine decarboxylase (ADC) and agmatine ureohydrolase (AUH). NaCl, KCl, LiCl, sucrose, and glycerol were used as solutes to prepare the resuspending media with various osmolalities. Regardless of whether the solutes were electrolytes or non-electrolytes, exposure of cells to low osmolality brought about instantaneous increases in both intra- and extracellular Put contents without significant changes in the contents of other polyamines. This acceleration in Put production was accompanied by no increases in the specific activities of ADC and AUH. On the other hand, when cells were exposed to the osmolality equivalent to 2 or 5% NaCl, all solutes except for glycerol did not cause a remarkable variation in the intracellular Put content, while the amount of Put in the medium varied depending on the solute used; sucrose and glycerol still greatly prompted Put production, as judged by high Put contents in the media, even at the osmolality equivalent to 5% NaCl. The cation efflux from cells, measured as the K+ release, was observed whenever the increase in Put production occurred. Furthermore, in vitro experiments showed that NaCl and KCl inhibited ADC to a similar extent, about 70% inhibition being observed at 200 mM. However, AUH was not affected by these compounds. These results suggest that the reduction in the concentrations of Na+ and K+ predominantly present in cells may cause the increase in activity of the preexisting ADC, which leads to the enhancement of Put production.

Aminooxyacetic Acid↗
PubMed1989

Formation of hydroxynorspermidine from exogenously added 1,3-diaminopropan-2-ol in Vibrio species.

When Vibrio parahaemolyticus AQ 3627 was grown in the presence of 1,3-diaminopropan-2-ol (OH-Dap), a new compound accumulated in the cells. This was identified as hydroxynorspermidine (OH-Nspd), N-(3-aminopropyl)-1,3-diaminopropan-2-ol, by gas chromatography-mass spectrometry and thin-layer chromatography. It was also synthesized enzymatically from OH-Dap by a cell-free preparation from this strain. All other Vibrio strains examined also showed the ability to synthesize this compound, but none of the non-vibrio organisms did, indicating that OH-Dap is an in vivo substrate for the enzyme responsible for biosynthesis of norspermidine characteristically present in vibrios. These results suggest that the ability to synthesize OH-Nspd from OH-Dap present in the growth medium may be useful as an additional identifying factor for the genus Vibrio.

Biotransformation↗
PubMed1988

Activities and properties of putrescine-biosynthetic enzymes in Vibrio parahaemolyticus.

The biosynthetic pathways for putrescine (Put) in Vibrio parahaemolyticus were delineated by measuring activities of the enzymes which would be involved in its biosynthesis. Experiments with labeled arginine and ornithine revealed that both of these amino acids were converted into Put by intact cells. The activities of three enzymes, arginine decarboxylase (ADC), ornithine decarboxylase (ODC), and agmatine ureohydrolase (AUH), were detected in cell extracts. ADC and ODC of V. parahaemolyticus were similar in the following properties to the corresponding enzymes of Escherichia coli: 1) both decarboxylases showed a pH optimum at 8.25 and required pyridoxal phosphate and dithiothreitol for full activity; 2) while ODC was considerably activated by GTP, ADC was only slightly; 3) both decarboxylases were inhibited by polyamines; 4) ADC was inhibited by difluoromethylarginine, a potent inhibitor of bacterial ADC. However, in contrast to the corresponding enzymes of E. coli, the V. parahaemolyticus ADC showed no requirement for Mg2+, and the AUH was active over a wide pH range of 8.5-9.5 with a maximum at pH 9.0. Furthermore, in all 6 strains tested, the activity of ADC was obviously high compared with that of ODC, and AUH was present with a relatively high activity. Cultivation of these strains at a suboptimal NaCl concentration (0.5%) resulted in a pronounced increase in both ADC and AUH activities. These observations suggest that the important pathway for Put biosynthesis in V. parahaemolyticus is the decarboxylation of arginine by ADC and the subsequent hydrolysis of its product, agmatine, by AUH.

Agmatine↗
PubMed1975

Studies on the etiology of milk intolerance in Japanese adults.

1. The incidence of milk intolerance is approximately 19% in Japanese adults when 200 ml of milk is given. However, a much greater incidence was assumed when considered under the criteria of Western standard. 2. The lactase activity was significantly greater in milk drinkers than non-drinkers. And, internationally, the active is higher in those nationalities whose milk consumption is greater. 3. Lactase is an adaptive enzyme and rather easily induced by lactose load feeding in animals. From the data of our own and of the literature, it was further confirmed that environmental factors play a more important role than genetic factors in the etio-pathogenesis of milk intolerance.

Adolescent↗