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Biomedical subjects

Y Seto

Publications and source records attributed to Y Seto.

At least 163 records · Page 9Linked to original sources
PubMed1984

AD-1590, a potent antagonist of lipopolysaccharide-induced fever in rabbits.

The antipyretic activity of AD-1590 (2-[8-methyl-10,11-0xodibenz[b,f]oxepin-2-yl]propionic acid), a non-steroidal anti-inflammatory drug with a novel chemical structure, was investigated in rabbits with lipopolysaccharide (LPS)-induced fever and monkeys with leucocytic pyrogen-induced fever. AD-1590 produced a dose-related inhibition of the LPS-fever at oral doses of 0.1 mg kg-1 or more (ED50 = 0.089 mgg kg-1). Its potency was 10-12, 20-35, 100-170, 400-540, greater than 1500 and greater than 2000 times that of ketoprofen, diclofenac sodium, indomethacin, ibuprofen, mefenamic acid and aspirin, respectively. The fever caused by leucocytic pyrogen was significantly inhibited by intravenous administration of 0.1-0.2 mg kg-1 of AD-1590 (10 mg kg-1 oral or i.v.) did not affect body temperature in afebrile rabbits or monkeys. These results suggest that AD-1590 shows a potent antipyretic activity in the rabbit and monkey and is a potent antagonist of LPS-fever.

Animals↗
PubMed1984

[Significance of human Tr cell in gastric cancer --with special reference to suppressor cell activity].

Peripheral blood lymphocytes from gastric cancer patients and normal donors were divided into T, non T, Tr, and T non-r cell fractions. Suppressor cell activity of each fraction and surface antigen of T cell subsets were investigated. T and Tr cell fractions activated by concanavalin A (Con A) significantly depressed the lymphocyte proliferative responsiveness (LP) to phytohemagglutinin (PHA) of responder autologous lymphocytes, but non T and T non-r cell fractions didn't. LP response to PHA of responder autologous cells were depressed by Tr cell fraction from gastric cancer patients without Con A activation, but not from normal donors. The percentage of Tr cells in T cells increased from 8.9% to 18.2% in gastric cancer patients, and from 4.7% to 9.5% in normal donors when lymphocytes were activated by Con A for 24 hours. The percentages of Tr cells reacting with OKT3, 4, and 8 monoclonal antibodies were 72.5%, 29.0% and 43.4%, respectively. Therefore, Tr cell was relatively enriched by OKT8 cell. The percentage of Tr cells and suppressor cell activity increased when normal lymphocytes were incubated with sera from gastric cancer patients for 24 hours and suppression by T, Tr and T non-r cell fractions 23%, 8% and 5%, respectively. From these results it is suggested that Tr cells contain suppressor precursors which can be activated by Con A in vitro and matured suppressor cells which have been already activated in vivo, and that higher proportion of suppressor precursors is found in gastric cancer patients as compared with normal donors. Furthermore, it is indicated that cancer sera may contain factors which induce suppressor cell and induction of suppressor cell activity requires the interaction between Tr cell and T non-r cell.

Antigens, Surface↗
PubMed1984

[Local immunotherapy for cancer].

As for the non-specific cancer immunotherapy concerned, the effect is limited and local use of immunopotentiators which could collect effector cells around tumor tissues might be the best way of cancer immunotherapy. Intratumoral or intraperitoneal administration of large-dose of OK-432 (100 KE) has been investigated since many years with favorable results. Side effects were minimum with a few days continuing slight fever elevation. From the immunohistological examinations using monoclonal antibodies, participation of killer T cells and NK cells was confirmed after intratumoral administration of large-dose OK-432. On the other hand, after intraperitoneal administration of OK-432, neutrophil leucocytes appeared at first on the 2nd to 4th day and they were followed by lymphocytes on the 4th to 5th day and finally appeared lot of macrophages on the 6th and later days. From the results of in vitro and in vivo experiments, these macrophages seemed to play the leading role in the cytostatic activities after intraperitoneal OK-432 administration. As for the fear of introducing suppressor cells after large-dose OK-432 administration, detailed studies on suppressor activities before and after operation for gastric cancer patients revealed no particular increase of suppressor cell activities after intratumoral and intraperitoneal administration of 100 KE OK-432 as compared with curative resection cases with no OK-432 administration.

Adjuvants, Immunologic↗
PubMed1983

Purification and properties of a cytochrome P-450 of a fungus, Fusarium oxysporum.

A cytochrome P-450 was isolated from a fungus, Fusarium oxysporum, which grew on a medium containing soybean oil as a sole carbon source. It was found as a heme protein that possess lipoxygenase activity, and seemed to exist in the soluble fraction of cell-free extracts. The cytochrome revealed multiplicity and could be separated into a least 3 fractions (A, B, and C). Two of them, termed Fusarium P-450A and -B, were highly purified. The complex of the ferrous Fusarium P-450 with carbon monoxide showed a Soret peak at 447 nm. The properties of the cytochromes (P-450A and -b) were closely similar to each other, the only detectable difference being in the pI (isoelectric point) value (5.2 and 5.0, respectively). The pI and molecular weight (48,000) values together with amino acid composition of Fusarium P-450 were similar to those of other cytochromes P-450 from various sources. Some other spectral properties as well as interactions with various ligands were also studied. Peroxidase or chloroperoxidase activity was not detected with Fusarium P-450.

Amino Acids↗
PubMed1983

[Enhancement of antitumor activity of Propionibacterium avidum in combined with neurotropin in tumor bearing mice].

The enhancement of antitumor activity of Propionibacterium avidum (P. avidum) in combination with Neurotropin (NSP) was investigated in C3H mice-MH 134 tumor system. P. avidum (0.5 mg) and NSP (20 mg/kg) were administered on day 2 and from day 1 to 7 after tumor inoculation, respectively. When mice were treated with P. avidum in combination with NSP, a significant prolongation in survival days was observed (P less than 0.01). Treatment with P. avidum alone produced prolongation in survival days, but NSP did fail. Increase of Con-A induced suppressor cell activity and depressed proliferative response of spleen cells were observed by the treatment with P. avidum. However, recovery of proliferative response to normal level and disappearance of suppressor cell activity were observed when NSP was combined. Thus, treatment by P. avidum in combination with NSP produced a significant prolongation in survival days and it may be depending on macrophage activation by P. avidum and on the restoration of T cell functions by NSP.

Animals↗
PubMed1983

The pharmacological profile of 2-(8-methyl-10,11-dihydro-11-oxodibenz[b,f]oxepin-2-yl)propionic acid (AD-1590), a new non-steroidal anti-inflammatory agent with potent antipyretic activity.

Anti-inflammatory, analgesic, antipyretic and gastrointestinal ulcerogenic activities of 2-(8-methyl-10,11-dihydro-11-oxodibenz(b,f]oxepin-2-yl)propionic acid (AD-1590), a new non-steroidal anti-inflammatory drug, were compared with indomethacin (INN: indomethacin) and other non-steroidal anti-inflammatory drugs (NSAID) in experimental animals. AD-1590 showed the potent inhibitory activity on acute and subacute inflammation such as carrageenin hind paw edema (oral ED50 = 1.35 mg/kg), acetic acid-induced increased vascular permeability (0.205 mg/kg), UV-erythema (0.295 mg/kg) and felt pellet-induced granuloma formation (1.7 mg/kg), and its potency was on the whole 2 to 3 times that of indomethacin. Oral analgesic ED50-values of AD-1590 were 0.245, 8.32 and 13.9 mg/kg in the writhing tests, and 2.45 mg/kg in the silver nitrate-induced arthritic pain test. Analgesic potency of AD-1590 was on the whole comparable to that of indomethacin. Against the pyrexia caused by two kinds of pyrogens (yeast and adjuvant), AD-1590 exerted a strong antipyretic action at oral doses as low as 0.02 to 0.1 mg/kg, and its potency (ED50 equal 0.0210 and 0.0406 mg/kg) was 8.7 to 11 times that of indomethacin. , AD-1590 displayed the antipyretic activity at low doses which were widely different from its anti-inflammatory and analgesic effective dose. The body temperature was not affected by 20 mg/kg p.o. of AD-1590 in the afebrile animals. AD-1590 was the strongest antipyretic drug among 10 NSAID tested. In rats, AD-1590 produced gastrointestinal ulcer similar to indomethacin, and its gastric ulcerogenicity (SUD50 equal 13.8 mg/kg p.o.) was about one-half that of indomethacin. The activity of AD-1590 in the fecal occult bleeding test in beagle dogs was weaker than that of indomethacin. The potency of AD-1590 (IC50 equal 0.78 mumol/l) as a prostaglandin synthetase inhibitor was about 2.7 times that of indomethacin in the in vitro test. The safety index (SUD50/ED50) of AD-1590 was larger than that of indomethacin, extremely large (the index equal 657 and 340) in the antipyretic activity. Besides, acute lethal toxicity of AD-1590 (oral LD50 equal 147 mg/kg in rats, 500 mg/kg in mice) was about 1/8 and 1/24 that of indomethacin. From these results, it was suggested that AD-1590 had extraordinarily potent antipyretic activity, potent anti-inflammatory activity superior to indomethacin, analgesic activity equivalent to indomethacin, and a wide safety margin.

Animals↗
PubMed1983

[Enhancement of in vitro lymphocyte proliferative response by vitamin B compounds].

The effects of Vitamin B compounds consisting of B1, B6 and B12 on the in vitro lymphocyte proliferative (LP) response were investigated. Vitamin B compounds failed to enhance the LP response of healthy controls but did enhance that of cancer patients, suggesting the recovery of depressed LP response to normal level by the treatment employing the compounds. The addition of Vitamin B compounds in the generation phase of Concanavalin-A induced suppressor cells significantly abrogated the activities. However, Vitamin B compounds produced no effect to neutralize the inhibitory effect of cancer sera on LP response.

Concanavalin A↗
PubMed1982

[Anti-inflammatory, analgesic and anti-pyretic activities of a non-steroidal anti-inflammatory drug, etofenamate, in experimental animals].

Anti-inflammatory, analgesic, and anti-pyretic activities of orally administered etofenamate, the diethylene glycol ester of flufenamic acid, were investigated in experimental animals. Against acetic acid-induced vascular permeability in mice and ultra-violet light-induced erythema in guinea pigs, etofenamate produced a dose related inhibition at doses of 40--320 mg/kg and 5--20 mg/kg, respectively. In rats, felt-pellet-induced granuloma formation and adjuvant-induced arthritis were significantly inhibited by repeated administration of etofenamate at doses of 20 mg/kg/day for 5 days and 40 mg/kg/day for 21 days, respectively. Etofenamate showed an inhibitory activity on the squeak response caused by flexing and extending the silver nitrate-induced arthritic joint in rats; and it produced a dose related anti-writhing activity at doses of 50--300 mg/kg and 10--80 mg/kg in mice and rats, respectively, in the acetic acid-induced writhing test. Etofenamate showed a significant anti-pyretic activity at doses of 0.2 mg/kg or more. These potencies of etofenamate were 0.5 to 1.6 times those of flufenamic acid. In particular, the anti-erythema, anti-arthritis, and anti-pyretic activities of etofenamate were approximately equivalent to or superior to those of flufenamic acid. From these results, it was suggested that etofenamate given orally, like other non-steroidal anti-inflammatory drugs, showed anti-inflammatory, analgesic, and anti-pyretic activities in experimental animals.

Analgesics↗
PubMed1982

[Anti-inflammatory activity of a non-steroidal anti-inflammatory agent, zomepirac sodium, in experimental animals].

Anti-inflammatory and gastrointestinal ulcerogenic activities of zomepirac sodium were investigated in experimental animals. The inhibitory activity of zomepirac sodium against carrageenin hind paw edema in rats, acetic acid-induced increase in vascular permeability in mice, and UV-erythema in guinea pigs was more potent than that of indomethacin. Anti-edema activity of zomepirac sodium was seen in adrenalectomized rats. Zomepirac sodium, like indomethacin, inhibited the delayed phase of hind paw edema produced by mixed phlogistics, but not the early phase mediated by histamine and serotonin in rats. Zomepirac sodium produced a dose-dependent inhibition against granuloma formation, established adjuvant arthritis, and development of adjuvant arthritis in rats; and its activity was slightly less potent than that of indomethacin. The inhibitory activity of zomepirac sodium on PGE2 biosynthesis in vitro was about one-third that of indomethacin. The ulcerogenic activity of zomepirac sodium was about 5 times weaker than that of indomethacin. From these results, it was suggested that zomepirac sodium was effective on various types of inflammation and showed particularly potent inhibitory activity against acute inflammation. These findings suggest that the mode of action of zomepirac sodium is similar to that of other acidic non-steroidal anti-inflammatory drugs.

Adrenalectomy↗
PubMed1982

[Anti-inflammatory and analgesic activities of a trans-cutaneous non-steroidal anti-inflammatory agent, etofenamate gel].

Anti-inflammatory and analgesic activities of topically applied etofenamate gel (5% etofenamate) were investigated in experimental animals. Etofenamate gel showed a dose related inhibition against vascular permeability caused by histamine in mice and ultra violet light-induced erythema in guinea pigs at doses of 10--100 mg/site and 25--200 (ED50 = 26.6) mg/site, respectively. The erythema was not inhibited with its topical application of 100 mg/site to the skin distant from the erythema. Granuloma formation, caused by felt-pellet implantation, was inhibited in a dose dependent manner by repeated application of etofenamate gel (10--100 mg/site/day). Etofenamate gel inhibited the pain-like responses in both the arthritic joint and the edematous hind paw of rats with 50--200 mg/joint and 100 mg/paw, respectively. In these tests, the vehicle gel did not show any significant activity. The potency of etofenamate gel was stronger than that of adrenal-extracts ointment (Mobilat) and approximately comparable to indomethacin ointment (1% indomethacin) in a weight basis of formulations. Topical application of etofenamate (0.5--2 mg/ear) resulted in a dose related decrease of contact hypersensitivity to oxazolone in mice, and its activity was nearly equipotent to flufenamic acid and about one-fourth that of indomethacin. From these results, it was suggested that etofenamate gel, applied topically to the inflamed tissue, showed a certain inhibitory activity against acute and subacute-chronic inflammation and inflammatory pain-like responses.

Administration, Topical↗
PubMed1981

Virus-induced alterations in insulin release in hamster islets of Langerhans.

After the inoculation of Golden Syrian hamsters with the TC-83 vaccine strain of Venezuelan encephalitis (VE) virus, a sustained diminution in glucose-stimulated insulin release and glucose intolerance of shorter duration develops. To understand better the mechanism of this defect in insulin release, we examined insulin secretion in response to several test agents in isolated perifused islets from control and 24-d post-VE virus-infected hamsters. 50 islets were used in all perifusion experiments, and data were expressed as total insulin released as well as peak response for each test agent during a 30-min perifusion period from control and VE-infected islets. After perifusion with 20 mM glucose, a 45% diminution of insulin release was noted in VE-infected islets in comparison with control islets, which in turn was similar to in vivo findings. However, following 1-mM tolbutamide stimulation, insulin release was similar in control and VE-infected islets. In separate studies, 1 mM tolbutamide, 10 mM theophilline, 1 mM dibutyryl cyclic (c)AMP, and 1 mM 8-bromo-cAMP resulted in statistically similar insulin-release curves in control and VE-infected islets. Additional experiments assessing [5-3H]glucose use in control and infected islets after 20 min of perifusion with 20 mM glucose revealed virtually identical values (239 +/- 30-control; and 222 +/- 27-VE-infected islets). Morphological and morphometric evaluation of VE-infected islets (21 d following virus inoculation) showed no changes in islet volume density, beta cell density, and beta cell granulation. Thus, VE virus induces a defect in glucose-stimulated insulin release from hamster beta cells that can be corrected by cAMP analogues and does not alter islet glucose use.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1981

In vivo distribution of 14C-labeled N4-behenoyl-1-beta-D-arabinofuranosylcytosine in mice.

In order to clarify the pharmacological characteristics of N4-behenoyl-1-beta-d-arabinofuranosylcytosine (BHAC) and 1-beta-D-arabinofuranosylcytosine (AraC) with regard to their distribution in vivo, 14C-labeled BHAC and 13C-labeled AraC were injected intravenously into mice. Their in vivo distribution was determined by whole-body macroautoradiography and by an oxidation method. The disappearance rates of BHAC[cytosine-2-14C] and BHAC[behenoyl-l-14C] from the blood were slower than that of AraC[cytosine-2-14C], and the elimination rates of BHAC[cytosine-2-14C] and BHAC[behenoyl-14C] into the urine and feces were also slower than that of AraC[cytosine-2-14C]. The total amounts of BHAC[cytosine-2-14C] and BHAC[behenoyl-1-14C] eliminated within 48 hr after the injection were small. AraC[cytosine-2-14C] was equally distributed in each organ, while large amounts of BHAC[cytosine-2-14C] were found in and the placentae. The BHAC[behenoyl-1-14C]level in the thymus was lower than that of BHAC[cytosine-2-14C]. A very low level of radioactivity was found in most of the organs 6 hr after the injection of Arac[cytosine-2-14C], but BHAC[cytosine-2-14C] was observed even 24 hr after the injection. Radioactivity was still found in the liver, spleen, kidneys and adrenal glands of mice injected with BHAC[behenoyl-1-14C] even after 72 hr. In pregnant mice, AraC]cytosine-2-14C] was transmitted to the fetuses, but only a very small amount of 14C-BHAC was transmitted to the fetuses.

Animals↗
PubMed1980

Clinical experiences with left gastric vena caval shunt in patients with esophageal varices.

Left gastric vena caval shunt (Inokuchi) was performed in four patients with liver cirrhosis; electively in two and prophylactically in two cases. The overall results have been satisfactory in terms of the effect on esophageal varices and postoperative complications. This procedure appeared to be superior to distal splenorenal shunt or other direct surgical procedures in several aspects. Since left gastric vena caval shunt does not require particularly elaborate surgical techniques and can be performed safely even in patients with considerably impaired hepatic function, it can be recommended as an ideal surgical procedure to be performed in elective and prophylactic surgical candidates.

Adult↗