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Biomedical subjects

T Mase

Publications and source records attributed to T Mase.

At least 73 records · Page 4Linked to original sources

Effects of cytogenin, a novel anti-arthritic agent, on type II collagen-induced arthritis in DBA/1J mice and adjuvant arthritis in Lewis rats.

The anti-arthritic effects of cytogenin (8-hydroxy-3-hydroxymethyl-6- methoxyisocoumarin) on type II collagen-induced arthritis in DBA/1J mice and adjuvant arthritis in Lewis rats were examined. Prophylactic treatment with cytogenin (30, 100 mg/kg) had a potent inhibitory effect on type II collagen-induced arthritis. Prophylactic or therapeutic treatment with cytogenin (10, 30 and 100 mg/kg) also had a potent inhibitory effect on adjuvant arthritis. In contrast to nonsteroidal anti-inflammatory drugs (NSAIDs), cytogenin (10, 30 and 100 mg/kg) had neither an anti-inflammatory effect on carrageenan-induced paw oedema in rats nor an analgesic effect on acetic acid-induced writhing in mice. These results suggest that the mode of the anti-arthritic action of cytogenin is different from that of NSAIDs and that cytogenin may become a useful drug for the treatment of rheumatoid arthritis.

Animals↗

A convenient evaluation of the stereoselectivity of lipase-catalyzed hydrolysis of tri-O-acylglycerols on a chiral-phase liquid chromatography.

A general method was developed using chiral-phase chromatography in order to evaluate the stereoselectivities of lipases-catalyzed hydrolysis of tri-O-acylglycerols independent of acyl groups. 1,2-Di-O-acyl-sn-glycerols or its enantiomer 2,3-di-O-acyl-sn-glycerols in the enzymatic reaction mixtures were derivatized to the key compound, 1,2-di-O-benzoyl-3-O-tert-butyldimethylsilyl-sn-glycerol 2 (+) or its enantiomer 2' (-), respectively. The enantiomers were separated on a chiral-phase HPLC, and the method was highly sensitive to determine the stereoselectivities of lipases.

Chromatography, High Pressure Liquid↗

Evaluation of intravascular hemolysis by haptoglobin administration after prosthetic valve replacement.

Although the measurement of serum haptoglobin (S-Hp) is of great use for evaluation of intravascular hemolysis, it is not applicable in patients with mechanical prosthetic valves because S-Hp is virtually absent. We administered haptoglobin preparation to 10 patients with Björk-Shiley mitral prosthetic valves and 10 patients with the same aortic prosthetic valves. Serum haptoglobin levels were measured periodically afterwards. The maximum haptoglobin levels (Hp (max)), serum, haptoglobin reducing rate ((Hp-delta Hp)/delta t) and expected haptoglobin disappearing time (hours) were obtained from the subsequent samples. The screening studies which were performed at the same time were not predictors of difference in the 2 groups. On the other hand, serum haptoglobin reducing rate and expected haptoglobin disappearing time indicated that hemolysis is higher in patients with an aortic prosthetic valve than with a mitral prosthetic valve. This haptoglobin administration test seems to be useful for the comparative examination of the intravascular hemolysis caused by the difference in the position of the prosthetic valve.

Adult↗

Crystallization and characterization of monoacylglycerol and diacylglycerol lipase from Penicillium camembertii.

A new lipase from Penicillium camembertii U-150, which is specific for monoacylglycerols and diacylglycerols, but not triacylglycerols, was purified as four active components using concanavalin-A-Sepharose column chromatography, crystallized in the form of needles, and its properties investigated. No significant difference was observed in substrate specificity, but molecular mass and other enzymatic properties, such as pH, heat stability and optimum pH and temperature, were clearly different between the unadsorbed and the three adsorbed components on concanavalin-A-Sepharose; the three adsorbed components were similar to each other and more stable than the unadsorbed component. On the other hand, after enzymatic removal of carbohydrates from the three adsorbed components, their enzymatic properties became similar to those of the unadsorbed component. The carbohydrates of this lipase contribute to the stability of the enzyme, but not to its enzyme activity. The amino acid compositions of the four components did not differ from each other, and tryptic mapping of the deglycosylated components and amino acid composition of the tryptic fragments were identical. The carbohydrate compositions of four intact components were, however, different from each other. All four components have the same polypeptide backbone and multiple forms of this lipase are due to the differences in composition of the carbohydrates bound in this lipase.

Amino Acids↗

Secretion of mono- and diacylglycerol lipase from Penicillium camembertii U-150 by Saccharomyces cerevisiae and site-directed mutagenesis of the putative catalytic sites of the lipase.

Yeast cells carrying intronless mono- and diacylglycerol lipase (MDGL) genes, constructed by recombination of the genomic gene and cDNA, secreted MDGL into the culture supernatant. Most of the yeast MDGL were extensively glycosylated while they had a similar glyceride specificity to that of native MDGL. Site-directed mutagenesis was used to directly confirm the involvements in enzyme activity of the presumptive amino acid residues to form the catalytic center of MDGL. These residues were conserved in the primary structure alignment of a lipase family from filamentous fungi. Mutant lipase proteins in which Ser83, Ser145, or His259 was replaced with glycine were secreted by yeast transformants as inactive proteins. Mutant proteins replacing Asp199 with glycine or asparagine were not detected in the culture supernatant. Replacing other two highly conserved aspartic acids (at positions 232 and 243) with glycine did not render the enzyme inactive. These results indicate that Ser83, Ser145, and His259 in MDGL, are essential to enzyme activity. Asp199 is also likely to be involved.

Amino Acid Sequence↗

[Acute aortic dissection in a patient with Marfan's syndrome and severe pectus excavatum--emergency surgical repairs of ascending aortic dissection and aortic regurgitation complicated by pectus excavatum in Marfan's syndrome].

A case of acute aortic dissection Stanford Type A occurring in a patient with Marfan's syndrome, complicated with aortic regurgitation and severe pectus excavatum, is reported with successful surgical correction. The patient was a 33-year-old woman, who suffered from severe back pain riding to work. An emergency operation consisting of Cabrol's procedure for aortic dissection Stanford Type A and sternal turnover for pectus excavatum was performed simultaneously. Because of the postoperative mediastinal bleeding the implanted sterno-costal complex was removed on the second POD and the prosthetic sternum was reimplanted on the tenth POD. The two-stage operation seems preferable in such an emergency case to avoid postoperative bleeding and infection.

Acute Disease↗

Cloning and structure of the mono- and diacylglycerol lipase-encoding gene from Penicillium camembertii U-150.

A gene (mdlA) encoding mono- and diacylglycerol lipase (MDGL) from Penicillium camembertii U-150 has been cloned using a 0.9-kb DNA fragment, generated by mixed oligodeoxyribonucleotide (oligo)-primed polymerase chain reaction (PCR), as a probe. Comparison of the nucleotide sequence of the gene and its cDNA clone, obtained by PCR, revealed the presence of two short introns (56 and 53 bp). Two transcription start points (tsp) were localized by primer extension analysis at 37 and 30 bp upstream from the ATG start codon and were preceded by the canonical TATAAA and CAAT sequences. The deduced amino acid (aa) sequence corresponds to 305 aa including a putative signal peptide of 26 aa. Despite significant differences in substrate specificity, the primary structure of the mature region shows homology (29% and 40%) to the triacylglycerol lipases from Mucor miehei and Humicola lanuginosa. Furthermore, the three residues presumed to form the catalytic site, serine, aspartic acid and histidine, are conserved. Primary structure comparisons of MDGL and triacylglycerol lipases are shown.

Amino Acid Sequence↗

Effects of YM264, a novel PAF antagonist, on puromycin aminonucleoside-induced nephropathy in the rat.

We investigated the effects of YM264, WEB2086, methylprednisolone and ticlopidine on puromycin-induced nephropathy in the rat. Puromycin produces marked proteinuria, hypercholesterolemia, and hypoalbuminemia. The structurally differing PAF antagonists YM264 and WEB2086 inhibited proteinuria and improved hypercholesterolemia and hypoalbuminemia. Methylprednisolone also exhibited a beneficial effect on these variables. However, ticlopidine, a platelet inhibitor, showed no inhibitory effect on nephropathy. These results indicate that PAF may play a major role in puromycin-induced nephropathy in the rat, and that PAF antagonists may prove of therapeutic value in the treatment of nephropathy in humans.

Animals↗

Pharmacological properties of YM461, a new orally active platelet-activating factor antagonist.

The antagonistic effect of YM461 [1-(3-phenylpropyl)-4-[2- (3-pyridyl)thiazolidin-4-ylcarbonyl]piperazine fumarate] against platelet-activating factor (PAF) was examined in several in vitro and in vivo systems. We found that YM461 inhibited [3H]PAF binding to rabbit platelet membranes with a pKi value of 8.90. YM461 inhibited PAF induced rabbit and human platelet aggregation with pA2 values of 7.52 and 7.29, respectively; the slopes of the Schild plots were 1.07 and 1.01, respectively. However, YM461 at 10(-4)M did not affect rabbit and human platelet aggregation induced by ADP, collagen, arachidonic acid or epinephrine. YM461 inhibited PAF induced death in mice with an ED50 (50% effective dose) value of 0.35 mg/kg p.o. YM461 at doses above 0.3 mg/kg i.v. inhibited PAF induced hypotension in rats. YM461 showed a dose-dependent inhibition of PAF induced hemoconcentration in rats with ED50 values of 0.15 and 0.21 mg/kg p.o., respectively, at 0.5 and 1 hr after oral administration. The anti-PAF effect of YM461 persisted more than 6 hr after 3 mg/kg p.o. in rats. YM461 inhibited the bronchoconstriction induced by PAF with an ED50 value of 1.2 mg/kg p.o. in anesthetized guinea pigs. Furthermore, the compound at doses above 3 mg/kg p.o. significantly inhibited antigen-induced anaphylactic asthma in conscious guinea pigs pretreated with mepyramine and propranolol. These results indicate that YM461 is a selective, potent and orally active PAF antagonist.

Administration, Oral↗

[Effects of YM-13650 on type I to type IV allergic reactions and immune responses in animals].

The effects of YM-13650 on experimental animal models of cell-mediated immune responses (type IV), antibody formation and type I to type III allergic reactions were investigated. YM-13650 in the dose range of 6.3 to 100 mg/kg, p.o., inhibited the picrylchloride-induced delayed type hypersensitivity (Pc-DTH) in mice when administered during the induction and the effector phases. The compound also inhibited the Pc-DTH enhanced by the pretreatment with cyclophosphamide, and even bilateral adrenalectomy failed to reduce the inhibitory effect of the compound on Pc-DTH in mice. YM-13650 in doses of 25 and 50 mg/kg, p.o., prolonged the survival time of allogenic skin grafts in mice. However, no significant effect was observed on hapten-specific IgE and HA antibody production and PFC formation in mice in doses up to 300 mg/kg, p.o. YM-13650 inhibited the passive Arthus reaction in guinea pigs and the reversed passive Arthus reaction in rats (type III). On the other hand, YM-13650 did not show any inhibitory effect on passive cutaneous anaphylaxis in rats (type I), Forssman shock in guinea pigs (type II) and carrageenin-induced paw edema in rats. These results indicate that YM-13650 suppresses not only cell-mediated immune responses but also type III allergic reactions without any influence on type I and type II allergic reactions as well as an acute inflammatory reaction.

Animals↗

[Surgical repair of partial anomalous pulmonary venous connection to the coronary sinus--a case report of PAPVC with mitral and tricuspid valve regurgitation in adult].

We have recently performed a successful repair of a total right anomalous pulmonary venous connection to the coronary sinus associated with mitral and tricuspid regurgitation. A 54-year-old female was inaccurately diagnosed as atrial septal defect associated with mitral and tricuspid regurgitation preoperatively. Operation revealed that all the right pulmonary veins connected to the coronary sinus. Mitral regurgitation which might be caused by distortion of the anterior leaflet was repaired by McGoon's technique. A Carpentire-Edwards ring was employed for the tricuspid annuloplasty. Repair of the atrial septal defect was undertaken with a pericardial septation patch which was sutured in place. The roof of the coronary sinus was widened by cutback, so that blood from the pulmonary veins could drain into the left atrium. The postoperative course was uneventful, except for a supraventricular arrhythmia.

Coronary Vessel Anomalies↗

Pharmacological properties of YM-11124, a selective immunosuppressive agent for cell-mediated immunity.

Effect of YM-11124 on cell-mediated immune responses, type I to type III allergic reactions and inflammatory reaction was determined in mice, rats and guinea pigs. YM-11124 inhibited picryl chloride- and methylated bovine serum albumin-induced delayed-type hypersensitivity reactions by the treatment during both the sensitization and the elicitation phases in mice. Bilateral adrenalectomy did not prevent the suppression of DTH response by YM-11124. YM-11124 significantly prolonged the survival time of allogenic skin grafts in mice. Furthermore, YM-11124 inhibited the passive Arthus reaction in guinea pigs and the reversed passive Arthus reaction in rats. However, YM-11124 did not affect the passive cutaneous anaphylaxis reaction in rats, Forssman shock in guinea pigs and paw edema in rats. These results indicate that YM-11124 suppresses not only cell-mediated immune responses (type IV allergic reactions) but also type III allergic reactions without influence on types I and II allergic reactions as well as acute inflammation.

Animals↗

Pharmacological properties of the orally active leukotriene antagonist [[5-[[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propyl]thio]-1,3,4- thiadiazol-2-yl]thio]acetic acid.

The anti-leukotriene effect of [[5-[[3-(4-acetyl-3-hydroxy -2- propylphenoxy)propyl] thio]-1,3,4-thiadiazol-2-yl] thio] acetic acid (YM-16638) was examined. In isolated guinea-pig ileum, YM-16638 antagonized the contractions induced by slow reacting substance of anaphylaxis (SRS-A) and leukotriene D4 (LTD4) with IC50 values of 6.0 x 10(-8) and 1.1 x 10(-7) mol/l, respectively. However, the compound at 10(-5) mol/l did not affect the contractions induced by histamine, acetylcholine, 5-hydroxytryptamine, prostaglandin (PG)E2 and PGF2 alpha. In isolated guinea-pig trachea, YM-16638 inhibited the contractions elicited by LTC4, LTD4 and LTE4 and its IC50 values were 5.7 x 10(-8), 1.6 x 10(-7) and 9.6 x 10(-8) mol/l, respectively. In isolated human bronchi, YM-16638 also antagonized the contractions induced by LTC4, LTD4 and LTE4 and its IC50 values were 6.0 x 10(-8), 1.2 x 10(-7) and 2.1 x 10(-8) mol/l, respectively. YM-16638 at the doses of 3 to 100 mg/kg p.o. inhibited the skin reaction induced by LTD4 in conscious guinea-pigs and its ED50 value was 17.9 mg/kg p.o. Successive oral administration of YM-16638 (50 mg/kg/d) for 10 days did not develop tolerance in its inhibitory effect against LTD4-induced skin reaction. Furthermore, the compound at the doses of 10 and 30 mg/kg p.o. significantly inhibited the antigen-induced bronchoconstriction in conscious guinea-pigs pretreated with mepyramine, propranolol and indomethacin. These results indicate that YM-16638 is a selective, potent and orally active leukotriene antagonist.

Animals↗

Isolated tissue and binding studies of YM-17690, a novel and non-analogous leukotriene agonist.

YM-17690, 3-[4-carboxymethoxy-3-[p-(4-phenylbutoxy) benzamido]phenyl]propionic acid, produced a dose-dependent contraction of guinea-pig ileum and its EC50 value was 1.6 X 10(-8) M. The response was not affected by pretreatment with atropine, mepyramine, indomethacin, dazoxiben and AA-861 (a 5-lipoxygenase inhibitor), but was inhibited by FPL-55712 (an LTD4 and LTE4 antagonist). YM-17690 induced dose-dependent contractions of guinea-pig lung parenchyma and trachea with EC50 values of 3.9 X 10(-9) and 2.2 X 10(-8) M, respectively. Pretreatment of these tissues with FPL-55712 resulted in a parallel shift of the YM-17690 dose-response curves to the right. The pA2 values for FPL-55712 in lung parenchyma and trachea were 7.41 and 8.21, respectively, and the slopes of the regression lines of Schild plots were 1.00 and 1.02, respectively. YM-17690 produced a dose-dependent inhibition of [3H]LTD4 binding to guinea-pig lung membranes and its pKi value was 9.28. However, the compound showed only 25% inhibition of [3H]TLC4 binding to guinea-pig hippocampus membranes, even at 10(-5) M. These results suggest that YM-17690 is a selective leukotriene (LTD4 and LTE4) agonist and that it will therefore be a valuable tool in the study of actions of leukotrienes and for the characterization of their receptors.

Animals↗