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Biomedical subjects

Y Sakurai

Publications and source records attributed to Y Sakurai.

At least 541 records · Page 30Linked to original sources
PubMed1984

Purification and characterization of an amidohydrolase for N4-long-chain fatty acyl derivatives of 1-beta-D-arabinofuranosylcytosine from mouse liver microsomes.

N4-Long-chain fatty acyl-1-beta-D-arabinofuranosylcytosine amidohydrolase, a metabolizing enzyme for N4-acyl derivatives of 1-beta-D-arabinofuranosylcytosine with long-chain fatty acids, was purified from mouse liver microsomes. The purification was accomplished by solubilization of liver microsomes with Triton X-100, diethylaminoethyl cellulose chromatography, gel filtrations, hydroxyapatite chromatography, and concanavalin A:Sepharose chromatography. On sodium dodecyl sulfate:polyacrylamide gel electrophoresis, the purified enzyme preparation produced a single protein band with a molecular weight of 54,000. The enzyme had an optimal pH of 9.0, and the Michaelis constant for N4-palmitoyl-1-beta-D-arabinofuranosylcytosine was 67 microM. The thiols such as dithiothreitol or 2-mercaptoethanol stabilized the enzyme and stimulated its activity. p-Chloromercuribenzoate, N-ethylmaleimide, diisopropylfluorophosphate, and phenylmethylsulfonyl fluoride strongly inhibited the reaction. Bovine serum albumin markedly stimulated the enzyme activity, whereas detergents such as Triton X-100, deoxycholate, and sodium dodecyl sulfate had little effect. The enzyme did not require monovalent or divalent cations. Among the series of N4-acyl derivatives of 1-beta-D-arabinofuranosylcytosine with different chain lengths of acyl residues, the purified enzyme preferentially hydrolyzed the derivatives with long-chain fatty acids (C12 to C18), and N4-palmitoyl-1-beta-D-arabinofuranosylcytosine was the most susceptible. The purified enzyme was inactive on various N-acylamino acids, amides, oligopeptides, proteins, N-acylsphingosines (ceramides), triglyceride, lecithin, and lysolecithin. These results suggest that N4-long-chain fatty acyl-1-beta-D-arabinofuranosylcytosine amidohydrolase may be a new type of linear amidase.

Amidohydrolases↗
PubMed1984

Metastasis after intravenous inoculation of highly metastatic variants of mouse tumors and the effects of several antitumor drugs on the tumors.

Tumor metastasis was examined after iv inoculation of highly metastatic variants of mouse tumors. Highly metastatic variants, B16-F10 and B16-BL6, of B16 melanoma origin and colon 26 NL-17 of colon adenocarcinoma 26 origin were used in the experiments. Formation of pulmonary metastasis was influenced by the mouse strain and age. Based on the results, experimental metastasis systems of these tumors were established, and the effects of chemotherapeutic agents were examined. 5-Fluorouracil and adriamycin were significantly effective for the suppression of pulmonary metastasis. The degrees of suppression of metastasis by these drugs were different with different tumor variants, but the sensitivity of the metastasis to the drug was similar to that of the parent tumor. Several aspects of the chemotherapy of metastasis are discussed.

Adenocarcinoma↗
PubMed1984

Isolation and characterization of highly and rarely metastatic clones from murine colon adenocarcinoma 26.

Three typical metastatic clones, designated N-1, N-4, and N-5, were isolated in vitro from a murine colon adenocarcinoma 26 cell line (Colon 26). The incidence of spontaneous metastasis was highest in N-4 (85%), moderate in N-5 and Colon 26 (50 and 53%, respectively) and lowest in N-1 (0%). The major target organ of metastasis was the lung. Among the clones, N-4 showed higher lung colonizing potential after intravenous inoculation, higher tumorigenicity and higher saturation density in culture. Cell-surface analysis of cloned cells by 125I-labeled lectins revealed significant reduction of the number of concanavalin A (Con A)-binding sites in highly metastatic N-4 cells. In sodium dodecyl sulfate-slab gel analysis of cellular glycoproteins, a 94,000-dalton component, which is reactive to Con A, was more intensely observed in N-1 as compared with other clones and parental Colon 26. These clones could provide a new model for the study of metastasis of colon carcinoma.

Adenocarcinoma↗
PubMed1984

Detection of early gastric cancer by panendoscopy.

With the implementation of a small-caliber panendoscope which was made according to our suggestion, we gradually replaced the conventional barium meal as the first line of the upper gastrointestinal tract examination by panendoscopy after 1976. The efficacy of panendoscopy for the early detection of gastric cancer in our 8-yr experience was investigated. In 910 matched pairs of patients subjected to "screening" fluoroscopy or panendoscopy two and six cases of early gastric cancer were detected respectively. Panendoscopy was superior to fluoroscopy in its sensitivity for detection of gastric cancer (86.4% vs. 80.0%), in its specificity (99.5% vs. 97.0%) and in its low false-positive rate (17.4% vs. 69.2%). After 1976, the detection of early gastric cancer increased year by year. The frequency of early gastric cancer detected by panendoscopy was about three times that of early gastric cancer detected by fluoroscopy (61.5% vs. 21.7% of all cancer). Early cancer located in the proximal third of the stomach and superficial esophageal cancer were detected only by panendoscopy. All gastric cancers that were overlooked by panendoscopy were in the gastric body. How to prevent such overlooking is discussed. In 24,000 panendoscopies we have encountered six complications (0.03%). The cost of panendoscopy and fluoroscopy is 6,500 yen and 11,000 yen respectively.

Adult↗
PubMed1983

Presynaptic modulation of the release of dopamine from striatal synaptosomes: differences in the effects of high K+ stimulation, methamphetamine and nicotinic drugs.

We examined the effects of nicotinic drugs on the metabolites of [3H]dopamine (DA) released from rat striatal synaptosomes in comparison with the effects of high K+ and methamphetamine stimulation. The pattern of outflow of [3H]DA and its metabolites induced by nicotine stimulants, acetylcholine (ACh), nicotine and lobeline, was different from that induced by high K+ and methamphetamine.

Animals↗
PubMed1983

Chemotherapy of disseminated gastric cancer. A joint effort of the Northern California Oncology Group and the Japanese Gastric Cancer Chemotherapy Group.

A consortium of Northern California and Japanese investigators studied 142 patients with advanced gastric adenocarcinoma. Patients were randomized to one of two combination chemotherapy programs in each nation (one common therapy shared and one therapy unique to each nation). Median duration of survival ranged between 5 and 45 weeks, depending on performance status, extent of disease, and chemotherapy program. More importantly, there was considerable comparability with respect to toxicity and outcome between patients in the US and Japan. Overall median survival was 26 weeks for Japanese and 27 weeks for US patients. This study helps provide the basis for future comparative multinational trials.

Adenocarcinoma↗
PubMed1983

Distribution and redistribution of pancreatic islet cell surface antigen reactive with islet cell surface antibody in the rat.

Antigens on the rat pancreatic islet cell surface were redistributed into patch and cap formation when the cells were incubated in the presence of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, in tissue culture medium 199 for 24 h, before addition of rat pancreatic islet cell surface antibody. In contrast, if the cells were cultured in tissue culture medium 199 supplemented with glucose (5.5 or 16.7mmol/l) and 10% heat-inactivated fetal calf serum without 3-isobutyl-1-methylxanthine, cap formation was not detectable. These results suggest that mobile antigen on the surface of pancreatic B cells can be induced to aggregate into patch and cap formations during conditions of increased cellular metabolism.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Multiple unit response in reward areas during operant conditioning reinforced by lateral hypothalamic stimulation in the rat.

Neural activities of various brain structures were examined during the acquisition and omission of a behavior. Forty-one rats were used. The positive reinforcer was the stimulation of the lateral hypothalamus, the effectiveness of which had been controlled in advance using the self-stimulation procedure. As original training, head movement during the presentation of an auditory signal was rewarded with the stimulation of the lateral hypothalamus. Following the acquisition of the behavior, omission training was given, during which inhibition of head movement was rewarded. In each session, multiple unit activity for 1 sec prior to the onset of the tone was compared with that during 1 sec tone presentation. In both training sessions, increases in unit activity to the tone, associated with the acquisition of the correct response, were found in the dorsomedial thalamus and the ventral tegmentum. In contrast, the neurons in the prefrontal cortex showed an increased response to the tone only during the omission training. These results suggest that the dorsomedial thalamus and the ventral tegmentum are related to the acquisition of the stimulus-reinforcer contingency, while the prefrontal cortex is related to behavioral inhibition in the omission learning.

Animals↗
PubMed1983

Potentiation of chemotherapeutic effect of vincristine in vincristine resistant tumor bearing mice by calmodulin inhibitor clomipramine.

Clomipramine, which is used as antidepressant and possesses calmodulin inhibitory activity, circumvented partly the vincristine resistance in vivo. Although vincristine alone at 30-200 micrograms/kg did not confer a significant therapeutic effect in vincristine resistant P388 leukemia (P388/VCR)-bearing mice, clomipramine at doses of 20 to 50 mg/kg administered daily for 10 d with vincristine enhanced the chemotherapeutic effect of vincristine in P388/VCR-bearing mice. Approximately a 30% increase in life span occurred. Although the circumvention of vincristine resistance was not achieved perfectly, it could be speculated that more than 98-99% of vincristine resistant tumor cells which could not be killed by vincristine alone could be killed by this approach.

Animals↗
PubMed1983

Tumor dependency of concanavalin A-induced potentiation of tumor cell immunogenicity.

The immunogenicity of concanavalin A (Con A)-treated tumor cells was examined in 4 histologically distinct tumors originated from 3 different strains of mice. In all of these tumors, Con A-treated tumor cells induced stronger tumor-specific immunity than Con A-free tumor cells as determined from the survival of sensitized mice after live tumor cell inoculation. However, Con A-induced potentiation of tumor cell immunogenicity was dependent on 2 experimental factors associated with the tumor cell vaccine preparation. One was the agent used for inhibiting in vivo transplantability of tumor cells and the other was the dose of tumor cell vaccine. In Meth A, Meth 1, and Lewis lung tumors, glutaraldehyde and Con A-treated cells, but not mitomycin C and Con A-treated cells, induced an enhanced immune resistance, whereas in L1210 leukemia, mitomycin C was more beneficial than glutaraldehyde. Higher doses of Con A-treated tumor cells (up to 10(7)) induced stronger immune resistance in Meth A and Meth 1 tumors, as was the case with L1210 tumor, whereas in Lewis lung tumor there existed an optimal vaccine dose. These results indicate a tumor species dependence of pretreatment agents and cell vaccine doses in inducing immune resistance, although Con A potentiated the immunogenicity of all the tumors tested.

Animals↗
PubMed1983

Establishment and properties of vincristine-resistant human myelogenous leukemia K562.

A vincristine (VCR)-resistant subline of human K562 myelogenous leukemia was established in vitro, and several clones with different susceptibilities to VCR were isolated by the limiting dilution technique. The most resistant clone (H-1) had a 17-fold greater resistance to VCR when compared to the parent K562 cells. The clone gradually lost the resistance during prolonged culture in vitro. These clones generally accumulated smaller amounts of VCR in their cells as compared to the parent cells. The size of H-1 clone cells was almost the same as that of the parent cells. The numbers of potential binding sites of VCR in the K562 cells and the resistant H-1 clone were almost the same. Similar results were obtained for P388 and its VCR-resistant subline. The cells derived from the VCR-resistant H-1 clone were highly cross-resistant to vindesine and moderately resistant to vinblastine. Cells derived from clone H-1 exhibited marginal degrees of cross-resistance to adriamycin, maytansine and VP-16-213, whereas VCR-resistant P388 leukemia cells exhibited significant resistance to these agents, especially to maytansine.

Cell Line↗
PubMed1983

Characterization of metastatic clones derived from a metastatic variant of mouse colon adenocarcinoma 26.

A spontaneously metastatic variant (P-26-select) was selected from the murine colon adenocarcinoma 26 after repeated (26 times) cyclic in vivo passage of tumor cells from the lungs of mice bearing s.c. tumors. Clones were established from the cultured P-26-select cell line. These clones, the parent [P-no-select (culture cell line of colon 26 without in vivo selection)] and the metastatic variant (P-26-select) were then studied using three different assays to determine their metastatic potential. These assays included experimental metastasis, spontaneous metastasis from a nonresected s.c. growing tumor, and spontaneous metastasis following the resection of a primary footpad tumor. In general, there was an agreement among the results of these three assays of metastases, i.e., if a variant was spontaneously metastatic, it was also metastatic in the other assays of metastases. However, some experimentally metastatic clones did not necessarily show a high spontaneous metastatic potential to the lung. These results might indicate that the metastatic variant (P-26-select) is populated by spontaneously metastatic clones and also by clones which possess a propensity to metastasize experimentally. The morphology and growth properties of the clones were compared also.

Adenocarcinoma↗
PubMed1983

Optimal treatment schedule and antitumor spectrum of 4-carbamoylimidazolium 5-olate (SM-108) in murine tumors.

By designing optimal administration schedules, it was found that 4-carbamoylimidazolium 5-olate (SM-108) showed an excellent antitumor potency against a number of murine tumors. The optimal administration schedule of SM-108 was an intermittent multiple administration, in which the drug was multiply administered to mice at definite intervals of less than 3 hr for about 1 day on Days 1, 5, and 9 following tumor implantation. Although usual daily administration of SM-108 exhibited poor efficacy, the intermittent multiple administration of SM-108 exhibited potent antitumor activity against a wide variety of tumors, such as Ehrlich carcinoma, P388, 6-mercaptopurine-sensitive and -resistant L1210, Lewis lung carcinoma, Colon 26 adenocarcinoma, and Sarcoma 180. Among them, Ehrlich carcinoma showed the most prominent susceptibility to SM-108. With the intermittent multiple administration of SM-108, complete suppression was obtained in both the ascitic and solid forms of this tumor over a wide dose range. The schedule dependency of the antitumor effect of SM-108 described above was reasonably explained by its in vitro growth-inhibitory effects and pharmacokinetics in the mice.

Animals↗