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Biomedical subjects

T Asano

Publications and source records attributed to T Asano.

At least 811 records · Page 45Linked to original sources

[Antitumor activity of schizophyllan (SPG) against syngeneic ACI/N rat tumor, AMC-60 fibrosarcoma and BC-47 bladder cancer].

The antitumor activity of schizophyllan (SPG) against syngeneic ACI/N rat tumor, AMC-60 fibrosarcoma and BC-47 bladder cancer was investigated. Intramuscular injection of SPG caused a marked suppression of AMC-60 tumor growth. Results obtained with cytotoxicity tests in vitro and lymphoblastogeneic response in vitro suggest the association of enhanced macrophage cytostasis and high reactivity of lymphoid cells with the resistance of the host to AMC-60 tumor. Moreover, SPG showed pronounced antitumor activity against BC-47 bladder cancer. The highest therapeutic effectiveness was obtained when SPG injection was started at an advanced stage of the tumor, 4 out of 15 rats treated being completely cured of cancer. Cytotoxicity tests in vitro and neutralization tests in vivo indicated the important role of cytotoxic lymphocytes as well as activated macrophages in the host defence mechanism against BC-47 cancer. This, taken together with the fact that the rats cured completely by SPG therapy acquired transplantation resistance to BC-47 cancer, shows that SPG may promote tumor immunity in the host.

Animals↗

Vasodilatory action of HA1004 [N-(2-guanidinoethyl)-5-isoquinolinesulfonamide], a novel calcium antagonist with no effect on cardiac function.

A novel compound, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004) was found to be a potent relaxant of blood vessels. Rabbit aortic strips contracted by 18 mM KCl relaxed in the presence of HA1004, with an ED50 value of 2.2 X 10(-6) M. The isolated guinea-pig atria on right ventricular papillary muscles did not respond to HA1004, even at a concentration of 3 X 10(-4) M. HA1004, like verapamil, produced a competitive inhibition of the Ca++-induced contraction of the depolarized rabbit aorta. The pA2 value of HA1004 for the Ca++-induced contraction was 6.60. Atropine, propranolol, theophylline or indomethacin had no effect on the HA1004-induced relaxation. HA1004 (3 X 10(-6) M) inhibited the contraction produced by Ca++ ionophore, A23187, whereas verapamil or diltiazem had no effect on this contraction, even at a concentration of 3 X 10(-5) M. Moreover, HA1004 produced a competitive inhibition of Ca++-induced contraction of the A23187-treated aorta and inhibited the phenylephrine-induced contraction elicited in ca++-free solution, thereby suggesting that this drug affects intracellular rather than extracellular Ca++. The present findings indicate that HA1004 is a novel calcium antagonistic vasodilator with no effect on cardiac function and is apparently of a different class of calcium antagonist from verapamil.

Animals↗

[The role of radiotherapy in the management of cancer of digestive organs: the liver, bile tract and pancreas].

Until February 1984, 75 patients have undergone radiotherapy using the following two methods: 1. During surgery, electron 3000 rads were given. 2. For external irradiation, X-ray or fast neutron was given with a TDF (time dose and fractionation factor) of 80-110. Hepatocellular carcinoma: There were 14 patients including 6 preoperative irradiation and 8 unresectable cases. Improvements were obtained image diagnostically in 9 of 13 patients. Serum AFP level decreased in 6 of 8 patients. And the resected specimens revealed degeneration or necrosis of the cancer tissue. Radiotherapy can given beneficial effect to the patients with tumor emboli within the portal vein, or even disappearance of the tumor emboli sometimes could be seen. Bile duct carcinoma: There were 30 patients including 12 with intraoperative irradiation. 2 irradiated during surgery and external irradiation, and 16 with external irradiation. More than 1-year survivals observed in 6 of 18 unresectable cases. The longest survival of non-curative operation was 6.5 years with treatment. Pancreas carcinoma: There were 31 patients including 29 unresectable and 2 resectable cases. Prolongation of survival time in unresectable patients was not obtained with an interval of 5 months at 50% survival rate. But some clinical complaints were relieved. We concluded that radiotherapy is useful to improve surgical curability by decreasing the cancer cell viability, to give a wider surgical indication if portal tumor emboli can be eliminated, to prevent early tumor recurrence, and to give some beneficial effects to unresectable or recurrent patients.

Adult↗

Reconstitution of catecholamine-stimulated guanosinetriphosphatase activity.

beta-Adrenergic receptors were partially purified from turkey erythrocyte membranes by alprenolol-agarose chromatography to 0.25-2 nmol/mg of protein, and the stimulatory guanosine 5'-triphosphate (GTP) binding protein of adenylate cyclase (Gs) was purified from rabbit liver. These proteins were reconstituted into phospholipid vesicles by addition of phospholipids and removal of detergent by gel filtration. This preparation hydrolyzes GTP to guanosine 5'-diphosphate (GDP) plus inorganic phosphate (Pi) in response to beta-adrenergic agonists. The initial rate of isoproterenol-stimulated hydrolysis is approximately 1 mol of GTP hydrolyzed min-1 X mol-1 of Gs. This low rate may be limited by the hormone-stimulated binding of substrate, since it is roughly equal to the rate of binding of the GTP analogue guanosine 5'-O-(3-[35S] thiotriphosphate) [( 35S]GTP gamma S) to Gs in the vesicles. Activity in the absence of agonist, or in the presence of agonist plus a beta-adrenergic antagonist, is 8-25% of the hormone-stimulated activity. Guanosinetriphosphatase (GTPase) is not saturated at 10 microM GTP, and the response to GTP is formally consistent either with the existence of multiple Km's or of a separate stimulatory site for GTP. The GTPase activity of Gs in vesicles is also stimulated by 50 mM MgCl2 in the presence or absence of receptor. Significant GTPase activity is not observed with Lubrol-solubilized Gs, although [35S]-GTP gamma S binding is increased by Lubrol solubilization.

Adenylyl Cyclases↗

Molecular sizes of photolabeled GABA and benzodiazepine receptor proteins are identical.

[3H]Muscimol was irreversibly incorporated into rat cerebellar membranes upon irradiation with ultraviolet light. GABA agonists and antagonists inhibited this incorporation. The reversible muscimol-binding decreased after photoaffinity-labeling of the membranes with muscimol. These results indicated that this irreversible incorporation is to the GABA receptor. Photolabeled GABA receptor protein showed its Mr of 50000 +/- 1000 in SDS-polyacrylamide gel electrophoresis. This molecular size is identical to that of the benzodiazepine receptor which was photolabeled with 3H-flunitrazepam.

Animals↗

Postoperative adjuvant immunotherapy of gastric cancer with BCG-cell wall skeleton. 3- to 6-year follow up of a randomized clinical trial.

The clinical effectiveness of immunotherapy with the cell wall skeleton of Bacillus Calmette-Guérin was assessed in a study involving 140 consecutive patients with gastric cancer, who were gastrectomized at a single institution from January 1976 through December 1978. These patients were randomized by an envelope method after operation and divided into three treatment groups: 'control', 'chemotherapy', and 'chemotherapy plus immunotherapy with BCG-CWS.' Only two patients who died during surgery were excluded, and a survey of survival periods was made on the remaining 138 patients in January 1982. As a result, statistically significant differences in the survival rate curve were observed between the control and chemotherapy plus immunotherapy groups (P less than 0.01), and between the chemotherapy and chemotherapy plus immunotherapy groups (P less than 0.05). These results emphasize effectiveness of BCG-CWS as an adjuvant immunotherapeutic agent in gastrectomized cancer patients.

Adult↗

A double-blind clinical evaluation of the effect of Nizofenone (Y-9179) on delayed ischemic neurological deficits following aneurysmal rupture.

The effect of Nizofenone (Y-9179), a vertebral protective agent, on delayed ischemic neurological deficits following subarachnoid hemorrhage (SAH) due to aneurysmal rupture was investigated by a cooperative double-blind clinical trials. Delayed ischemic neurological deficits following SAH are closely associated with the occurrence of vasospasm, and the effectiveness of any cerebral protective agent depends on sufficient coverage by the drug over the period around the onset of ischemic insult. Therefore, the study was designed so that the effect of Nizofenone could be analyzed in terms of these two factors. In patients admitted within day 9 of SAH, drug administration was immediately initiated and continued for 5 days. When delayed ischemic neurological deficits occurred, angiography was carried out to confirm the presence of vasospasm, and then drug administration was extended for an additional 5 days. Ten of the 100 cases enlisted in the study were excluded prior to code-breaking because of the occurrence of severe complications not related to vasospasm. Out of the 42 cases of the Nizofenone group and 48 of the placebo group, 25 and 29 developed vasospasm, respectively. Thus Nizofenone did not prevent vasospasm. Of the 25 cases of the Nizofenone group with vasospasm, 13 cases received sufficient drug coverage around the onset of vasospasm. The placebo group, the total Nizofenone group, and the Nizofenone group with sufficient drug coverage were stratified according to the occurrence of vasospasm. The disability status index one month after admission and the neurological functions, such as motor and speech functions, of each group were then compared. In patients who developed vasospasm, only the Nizofenone group with sufficient drug coverage had a significantly better outcome than the placebo group (p less than 0.05). No particular side effect of Nizofenone was observed. Thus, the results indicate that Nizofenone may be useful in the therapy of delayed ischemic neurological deficits following SAH, although the effect of the drug may be considerably influenced by the timing of its administration.

Adult↗

Identification of 5-hydroxy eicosatetraenoic acid in cerebrospinal fluid after subarachnoid hemorrhage.

To detect and identify lipid peroxides in the CFS following subarachnoid hemorrhage (SAH), CSF samples were obtained sequentially from 10 patients who developed typical vasospasm and were analyzed by HPLC and gas chromatography-mass spectrometry. One of the peaks appearing on the 7th day after SAH was identified as 5-hydroxy eicosatetraenoic acid. On HPLC, an identical peak was detected in samples from other SAH patients. The results gave unequivocal evidence that peroxides of arachidonic acid are present in the CSF following SAH, and a correlation between them and the occurrence of vasospasm seemed likely. The hypothesis that lipid peroxides are involved in the genesis of vasospasm deserves further investigation.

Chromatography, High Pressure Liquid↗

Characterization of the solubilized GABA and benzodiazepine receptors from various regions of bovine brain.

GABA and benzodiazepine receptors were solubilized from bovine cerebral cortex, cerebellum, and hippocampus and then partially purified by gel filtration and characterized. The apparent molecular weights of all these receptors were determined to be 600,000-650,000 by gel filtration, the sedimentation coefficients being 11.0-11.3 S by sucrose density gradient centrifugation. [3H]Muscimol was bound to two classes of sites in fractions from all three regions, and [3H]flunitrazepam bound to one class of sites. A comparison of the ratios of Bmax for flunitrazepam binding to Bmax for muscimol binding revealed that the fractions from the hippocampus exhibited a much higher ratio of benzodiazepine binding sites than were detected in fractions from the cortex and cerebellum. GABA agonist and antagonist inhibited [3H]muscimol binding to the fractions from these regions, at similar concentrations. Benzodiazepine agonists and antagonists also inhibited [3H]flunitrazepam binding in these three fractions, with similar potency. CL 218,872, however, inhibited [3H]flunitrazepam binding in the cerebellar fraction with the lowest IC50 value and that in th hippocampal fraction with the highest IC50 value. Hill coefficients for CL 218,872 inhibition were 0.98, 0.64, and 0.58 for cerebellum, cortex, and hippocampus, respectively.

Animals↗

Brain free fatty acids, edema, and mortality in gerbils subjected to transient, bilateral ischemia, and effect of barbiturate anesthesia.

Brain free fatty acids (FFAs) and brain water content were measured in gerbils subjected to transient, bilateral cerebral ischemia under brief halothane anesthesia (nontreated group) and pentobarbital anesthesia (treated group). Mortality in the two groups was also evaluated. In nontreated animals, both saturated and mono- and polyunsaturated FFAs increased approximately 12-fold in total at the end of a 30-min period of ischemia; during recirculation, the level of free arachidonic acid dropped rapidly, while other FFAs gradually decreased to their preischemic levels in 90 min. In treated animals, the levels of total FFAs were lower than the nontreated group during ischemia, but higher at 90 min of reflow, and the decrease in the rate of free arachidonic acid was slower in the early period of reflow. Water content increased progressively during ischemia and recirculation with no extravasation of serum protein, but the values were consistently lower in the treated group. None of the nontreated animals survived for 2 weeks; in contrast, survival was 37.5% in the treated group. It is suggested that barbiturate protection from transient cerebral ischemia may be mediated by the attenuation of both membrane phospholipid hydrolysis during ischemia and postischemic peroxidation of accumulated free arachidonic acid.

Anesthesia, General↗

Acute retinal necrosis.

We treated 2 patients with unilateral acute retinal necrosis in association with uveitis. The disorder began as anterior uveitis, secondary glaucoma, and retinal vasculitis, and then developed into retinal necrosis within a few months. The aetiology was obscure and the appropriate treatment debatable. We also review reports of patients showing the same clinical characteristics, termed Kirisawa-type uveitis and bilateral acute retinal necrosis, and believe the disorders to be identical.

Acute Disease↗