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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 901 records · Page 50Linked to original sources

The protein A-gold technique. Use in the immunoelectron microscopic study of the teleost growth hormone.

By the application of the protein A-gold technique for immunocytochemistry of the tilapia pituitary growth hormone (GH), our electron micrographs revealed that the antigenicity of tilapia GH and the cytoplasmic structure were well preserved in the tissues fixed with periodate-lysine-paraformaldehyde followed by osmium tetroxide postfixation. Using the specific antiserum against tilapia GH, the immunoreactive gold particles of 20-40 nm in size were located on secretory granules (200-300 nm in diameter) exclusively of one cell type in the proximal pars distalis identified as GH cells on the basis of their ultrastructural characteristics. This technique is considered to be fairly efficient for the detection of intracellular antigenic sites on ultrathin sections.

Animals↗

Antitumor activity and toxicity of ACNU, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitroso urea hydrochloride, comparing two divided doses and a single dose.

In order to determine whether it is possible to reduce the toxicity of the nitrosoureas, including the delayed type of hematologic toxicity, without diminishing antitumor activity by administering the drug according to a new treatment schedule other than the single high-dose treatment schedule, we examined the antitumor activity against murine tumors and toxicities to host mice of a nitrosourea derivative, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1- nitrosourea hydrochloride (ACNU), which was administered according to two divided doses schedule. Experimental results indicated that the toxicity of ACNU with respect to lethality, as well as weight loss of host mice, was alleviated by administering ACNU (IV) at one-half of LD10 (20 mg/kg) on 2 successive days. However, no impairment of the antitumor activity of ACNU in various murine tumor systems was observed in comparison with that of ACNU administered according to the single high-dose schedule. The delayed type of hematologic toxicity (leukopenia) could not be alleviated by this treatment schedule.

Animals↗

Intra-arterial administration of heated albumin microspheres containing mitomycin C to rabbits with VX-2 tumor.

In an attempt to enhance antitumor effects, we prepared heated albumin microspheres containing mitomycin C (MMC). These MMC microspheres have an average diameter of 45 +/- 8 micrometers and contain about 5 per cent of MMC. The intra-arterial MMC microsphere treatment, for albino rabbits with implanted VX-2 tumor, increased remarkably the tissue MMC levels, compared to that with conventional MMC, and resulted in conspicuous antitumor efficacy. This approach to antitumor chemotherapy should be effective for selected patients with malignant tumor receiving a blood supply from an end-artery.

Animals↗

Clinical evaluation of schizophyllan adjuvant immunochemotherapy for patients with resectable gastric cancer--a randomized controlled trial.

Adjuvant immunochemotherapy using Schizophyllan (SPG), an extract from the culture broth of Schizophyllum commune Fries, was prescribed at random for 326 Japanese patients with resectable gastric cancer. The overall survival rates for 3 years did not differ between the SPG and control groups. In 62 patients with stage I gastric cancer and 67 with stage II, there was little difference in the 3-year survival rates. The survival rates for 100 patients with stage III were enhanced at p = 0.0811 in the SPG group, as compared to the controls. The survival rates in 97 patients with stage IV cancer were much the same. These results warrant further application of this immunopotentiating drug for treating patients with resectable gastric cancer.

Clinical Trials as Topic↗

Effect of caerulein administration on portal plasma somatostatin in dogs.

The effect of administration of synthetic caerulein on canine plasma somatostatin concentration in the portal vein was investigated using specific radioimmunoassay of acid-acetone extracted plasma. Gel chromatography revealed that the main component of the plasma somatostatin in the portal vein was identical with somatostatin-14. After administration of caerulein (5 ng/kg), the somatostatin level increased significantly while the gastrin level remained unchanged. These results suggested that caerulein affects D cell function but not gastrin secretion.

Animals↗

Placental transfer of ritodrine hydrochloride in sheep.

The purpose of this study was to examine the placental passage of ritodrine hydrochloride in relation to the drug's effects on the fetal circulation. Studies were carried out on nine nulliparous pregnant (120-140 days) ewes with chronically implanted cannulae for measurements of maternal and fetal arterial pressures and for blood sampling. One group of animals received sequential infusions of doses ranging from 0.1 to 30 micrograms/kg per min for 30 min (group 1). A second group was given a constant infusion of the drug at a dose of 3.0 micrograms/kg per min for 4 h (group 2). The peak concentrations of ritodrine in maternal and fetal blood were determined by radioimmunoassay. In group 1 they were 313.4 +/- 24.1 ng/ml (mean +/- S.E.) and 12.6 +/- 3.7 ng/ml at the finish of 30.0 micrograms/kg per min infusion for maternal and fetal blood, respectively. In group 2, maternal drug levels were 81.3 +/- 20.4 ng/ml after 30 min and 95.9 +/- 17.1 ng/ml after 4 h of the infusion. Fetal plasma concentrations increased slowly from trace levels at 30 min to 3.3 +/- 0.7 ng/ml at 4 h. Fetal blood pressure and heart rate did not show any significant changes during and after the infusion of ritodrine in both treatment groups. Our findings demonstrate the maternal administration of ritodrine produces no significant effects on the circulatory system of the fetal lamb because of the low transplacental passage of this drug.

Animals↗

The protective effect of vitamin E on cerebral ischemia.

Using the "canine model of the completely ischemic brain regulated with a perfusion method," the effects on cerebral ischemia of vitamin E, which is known to act as an antioxidant, were investigated. After pretreatment with vitamin E by oral or intravenous administration, cerebral blood flow was reduced to 1/10th the normal state and, 1 hour later, allowed to return to normal. Subsequent changes in electrical activity were observed, and the effects of vitamin E were evaluated. In the control group, no recovery of electrical activity was seen. In the groups given vitamin E, the recovery time was significantly shortened in the dogs given 30 mg/kg of vitamin E intravenously. Furthermore, in the groups treated with vitamin E, distinct recovery of electroencephalographic potentials at 3 hours after recirculation was apparent. These effects were more favorable in the case of intravenous administration than in the case of oral administration. These experimental results indicate that the administration of vitamin E is effective in protecting the brain from cerebral ischemia.

Animals↗

Characterization of intermediate-molecular-weight acid phosphatase from bovine kidney cortex.

The distribution of acid phosphatases of intermediate molecular weight was determined in various mammalian tissues. The intermediate-molecular-weight acid phosphatases (designated P-II-1 and 2) comprised about 25% of the p-nitrophenyl phosphatase activity in the supernatant of bovine kidney cortex homogenate. The P-II-1 and 2 purified 2,000 fold showed the pI values of 5.9 and 5.7, respectively, on isoelectric focusing. Apparent molecular weights of both P-II-1 and 2 were estimated to be 42,000 by Sephadex G-100 gel filtration and 44,000 by SDS-polyacrylamide disc gel electrophoresis. Both the enzymes catalyzed the hydrolysis of a wide variety of natural phosphomonoesters, except for the phosphoproteins phosphoserine and o-phosphocholine. The enzymes showed a high activity on pyridoxal phosphate, beta-glycerophosphate, and 2'-AMP. The optimum activity pH was near 5 with p-nitrophenyl phosphate, but was shifted to the neutral range when pyridoxal phosphate was the substrate. The cations Hg2+ and Ag+ had a marked inhibitory effect. Neither enzyme was inhibited significantly by L-(+)-tartrate or pCMB. The two other types of acid phosphatases, the high-molecular-weight (designated P-I) and low-molecular-weight (designated P-III), were also purified to homogeneity from bovine kidney cortex, and were compared with P-II from several aspects including substrate specificity and susceptibility to various compounds.

Acid Phosphatase↗

Histamine disposition in endothelial specific granules of the toad aorta.

High-performance liquid chromatography revealed that toad aorta delivered appreciable concentrations of histamine into the perfusate when perfused by Ringer's solution containing the histamine liberator. Electron micrographs of this vessel after the perfusion showed an expulsion of the endothelial specific granules into the vascular lumen. These results support to our previous hypothesis that the granules are a reservoir site of histamine and might take an important role in the regulation of vascular tone.

Animals↗

The utilization of carnosine in rats fed on a histidine-free diet and its effect on the levels of tissue histidine and carnosine.

Carnosine can support the growth of rats fed on a histidine-free diet. Rats fed on the histidine-free diet lost weight rapidly for a few days, then remained at a relatively constant weight for 2 weeks at least. However, rats fed on a 0.90% carnosine diet, which contains histidine equimolar to that in a 20% casein diet, increased their weight at the same rate as rats fed on a 20% amino acid diet simulated with casein. On the other hand, the growth of rats fed on a 5% carnosine diet was about 70% compared with that of control rats fed on the 20% amino acid diet for a 2-week experimental period. Carnosinase activity was not significantly affected in the kidney of rats fed on the histidine-free or the 5% carnosine diet. On the other hand, carnosinase activity in the small intestine of rats fed on the histidine-free diet was significantly increased. Histidine content of serum of rats fed on the histidine-free diet decreased to 1/3 of that of control rats, while that of rats fed on the 5% carnosine diet increased to about 14 times. Carnosine content of rat gastrocnemius muscle increased with carnosine content of diets, followed by an increase of histidine in the muscle. However, carnosinase activity of gastrocnemius muscle was not affected by carnosine in diets.

Animals↗

Regulation of immune responses via genetically-restricted cellular interactions. I. Augmentation of antibody responses by idiotype-specific enhancing B lymphocytes.

We previously reported that B lymphocytes obtained from BALB/c mice that had been immunized with M104E myeloma protein have an idiotype-specific enhancing activity for anti-dextran B1355S antibody responses in vivo. The enhancing cells were Thy-1-, Lyt-1-,2-, nylon wool-adherent and rabbit anti-mouse immunoglobulin (RAMG) dish adherent. The in vitro analysis described in this report also revealed that the enhancing cells had a B cell phenotype and were specifically enriched in M104E or J558 myeloma protein-coated dishes but not by irrelevant monoclonal antibodies. The significance of these B-B cell interactions were analyzed in vitro by using various Igh-1 and H-2 congeneic strains of mice. The idiotype immune B lymphocytes obtained from BALB/c and BAB-14 could enhance the antidextran antibody responses of BALB/c B lymphocytes in an idiotype-specific manner. On the other hand, C.AL-20 and CB-20 strains could not induce the idiotype-specific enhancing B cell activity in dextran-immune BALB/c B cells. These results suggest that the capability of enhancing B cell induction is related to the producibility of the respective idiotype in that strain of mice. Moreover, the B cells obtained from BALB/c mice immune to the idiotype cooperated well with the dextran-immune B cells of BALB/c but not of BALB.K and vice versa. These results indicate that successful cooperation between those two types of B lymphocytes requires the same MHC haplotype. The roles of these genetically restricted cellular interactions in the immune system are discussed.

Animals↗

[Experimental study of cerebral protective effect on cerebral ischemia of various antioxidants and other agents. With special reference to the combined treatment of mannitol, vitamin E, dexamethasone and perfluorochemicals].

We have previously reported that the combined administration of mannitol and perfluorochemical blood substitutes is evidently effective in protecting the brain from cerebral ischemia. This experimental study was designed to develop more effective method in suppressing brain infarction than the combined treatment of mannitol and PFC. Using the "Canine model of complete ischemic brain regulated with a perfusion method" in which it is possible to control the degree of blood flow to a cerebral hemisphere via a perfusion pump, the effect of eight agents including six kinds as the free radical scavenger on cerebral ischemia was investigated. Eight agents were mannitol, vitamin E (Vit. E), dimethyl sulfoxide (DMSO), vitamin C, glycerol, nizofenone (Y-9179), dexamethasone (Dexa.) and suloctidil (MY-103). After pretreatment with each agent, blood flow was reduced via the pump to 1/10 of the normal state and 1 hour later, return to the normal state was allowed. Subsequent changes in EEG were observed and the effects of the drugs evaluated. In the control group, no recovery of electrical activity was seen, but in six groups among eight treated groups, i.e., treated with mannitol, Vit. E, DMSO, MY-103, Y-9179 and Dexa, gradual emergence of slow waves was observed. And more favorable effects were found when the combined administration of mannitol, Vit. E and Dexa was made in the same experimental schedule as compared with the single administration of each of these drugs. Furthermore in the animals administered with PFC in combination with mannitol, Vit. E and Dexa, flattening of electrical activity could not be seen throughout the period of severe ischemia. Moreover, the power of electrical activity recovered nearly to the preischemic state immediately after recirculation. Although the possible mechanisms are not yet completely clarified, the present results are thought to indicate that this new combination therapy utilizing PFC with mannitol, Vit. E and Dexa may be useful in the treatment of cerebral ischemia.

Animals↗