Biomedical subjects

T Mase

Publications and source records attributed to T Mase.

At least 55 records · Page 3Linked to original sources

PubMed1997

N-[2-[(substituted chroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylamines: synthesis and wide range of antagonism at the human 5-HT1A receptor.

A series of N-[2-[(substituted chroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylamines was prepared and examined for their 5-HT1A receptor antagonist activity. The parent compound 3a and seven analogs bearing five kinds of substituents on the chroman ring were prepared from the corresponding 8-hydroxychroman intermediates. Radioligand binding assays proved the compounds 3a-h to have high affinity for the rat hippocampal 5-HT1A receptor with varied selectivity for adrenaline alpha1 and dopamine D2 receptors. Their antagonism was evaluated in a forskolin-stimulated adenylate cyclase assay performed with CHO cells expressing the human 5-HT1A receptor. Among the series, the C6-fluoro analog 3c showed both extremely potent affinity (Ki = 0.22 nM) and antagonism (EC50 = 13 nM) for the 5-HT1A receptor. Correlation analysis using substituent descriptors revealed a linear and negative correlation between molar refractivity of the C6-substituent and the binding affinity expressed in pKi.

Animals↗

PubMed1997

Remyelination in the rat dorsal funiculus following demyelination by laser irradiation.

Excimer laser (KrF excimer laser, 248 nm wavelength) was used to damage cellular components in the dorsal funiculus at the lumbar level (L2) of the rat spinal cord. An open lesion was not found at the irradiation site on the spinal cord. However, the cytological examination revealed that cellular components were damaged to the depth of 200-500 microm from the pial surface. The characteristic feature was that at the border of the lesion, many axons remained naked but intact after their myelin sheaths had been completely disintegrated. Such naked axons were subsequently remyelinated by mature or immature glial cells. Mature oligodendrocytes, while retaining their cytoplasmic processes connected with the myelin sheaths of unaffected axons, extended new cytoplasmic processes on nearby naked axons and made new myelin sheaths around them. In contrast, 7 days after the irradiation, numerous immature glial cells appeared in association with naked axons, and some of them were differentiated into oligodendrocytes forming thin myelin sheaths on naked axons. These findings suggest that demyelinated axons can cause the proliferation and probably dedifferentiation of the oligodendrocyte lineage. The use of lasers provides a unique experimental model of demyelination and remyelination in the central nervous system of adult mammals.

Animals↗

PubMed1997

2-(3-Pyridyl)thiazolidine-4-carboxamides. 1. Novel orally active antagonists of platelet-activating factor (PAF).

In a search for novel platelet-activating factor (PAF) antagonists, we found that 1-(3-phenylpropyl)-4-[2-(3-pyridyl)thiazolidine-4-carbonyl] piperazine (3x) showed in vitro and in vivo PAF-antagonistic activities. Introduction of functional groups at the benzylic methylene carbon of 3x afforded some compounds with more potent PAF-antagonistic activity than 3x. Among them 1-(3-methyl-3-phenylbutyl)-4-[2-(3-pyridyl) thiazolidine-4-carbonyl]-piperazine fumarate (3al, YM264) was found to be one of the most potent PAF antagonists.

Animals↗

PubMed1997

Efficient expression of mono- and diacylglycerol lipase gene from Penicillium camembertii U-150 in Aspergillus oryzae under the control of its own promoter.

The gene, mdlA, coding for mono- and diacylglycerol lipase from Penicillium camembertii U-150 was expressed efficiently in Aspergillus oryzae under the control of its own promoter. The gene product was secreted into the culture medium with a highest productivity of 1 g/liter and correctly processed at both N- and C-termini. KEX2-like processing was suggested to occur at the C-terminus in both A. oryzae and P. camembertii. Specific activity and substrate specificity of the purified recombinant protein were also almost the same to that of native protein but the extent of N-glycosylation in the recombinant protein was about half of that of the native protein. The presence of introns did not seem to affect the gene expression. The mdlA expression was induced by lipids and regulated transcriptionally in A. oryzae as well as P. camembertii. Promoter deletion analysis showed that the region between the positions at -382 and -554 bp from the translation initiation point was important to the higher expression of mdlA. The promoter sequence of mdlA was compared to that of the Geotrichum candidum lipase gene, which is also reported to be inducible by lipids, with three commonly observed oligonucleotide sequences.

Aspergillus oryzae↗

PubMed1997

[A case of thymic cyst and thymoma with myasthenia gravis].

A case of 53-year-old male with thymic cyst was reported. We established diagnosis for myasthenia gravis. The chest CT and MRI demonstrated a cystic and mass lesion on the anterosuperior mediastinum. This finding suggested a thymic cyst and tumor with myasthenia gravis. The extended thymectomy was performed. Histological examination demonstrated the clear separation of the mixed type thymoma and the thymic cyst. The few reported cases of thymic cyst and thymoma with myasthenia gravis were reviewed.

Humans↗

PubMed1996

Dopamine D3 and D4 receptor antagonists: synthesis and structure--activity relationships of (S)-(+)-N-(1-Benzyl-3-pyrrolidinyl)-5-chloro-4- [(cyclopropylcarbonyl) amino]-2-methoxybenzamide (YM-43611) and related compounds.

In this study, we synthesized a series of (S)-N-(3-pyrrolidinyl)benzamide derivatives, 1, 2a-d, 5a-1, and 7, and their enantiomers, (R)-1 and (R)-5c-e, and evaluated their binding affinity for cloned dopamine D2, D3, and D4 receptors and their inhibitory activity against apomorphine-induced climbing behavior in mice. The results indicate that D2, D3, and D4 receptors have different bulk tolerance (D4 > D3 > D2) for the substituent of the 4-amino group (R1) on the benzamide nuclei and that cyclopropyl-, cyclobutyl-, and cyclopentylcarbonyl groups likely possess adequate bulkiness with respect to D3 and D4 affinity and selectivity over D2 receptors in this series. The results also suggested that the N-substituent (R2) on the pyrrolidin-3-yl group performs an important role in expressing affinity for D2, D3, and D4 receptors and selectivity among the respective subtypes. One of the compounds, (S)-(+)-N-(1-benzyl-3-pyrrolidinyl)-5-chloro-4-[(cyclopropylcarbonyl+ ++) amino]-2-methoxybenzamide (5c) (YM-43611), showed high affinity for D3 and D4 receptors (Ki values of 21 and 2.1 nM, respectively) with 110-fold D4 selectivity and 10-fold D3 preference over D2 receptors and weak or negligible affinity for representative neurotransmitter receptors. Compound 5c displayed potent antipsychotic activity in inhibiting apomorphine-induced climbing behavior in mice (ED50 value, 0.32 mg/kg sc).

Animals↗

PubMed1996

The consequences of engineering an extra disulfide bond in the Penicillium camembertii mono- and diglyceride specific lipase.

The extracellular lipase from Penicillium camembertii has unique substrate specificity restricted to mono- and diglycerides. The enzyme is a member of a homologous family of lipases from filamentous fungi. Four of these proteins, from the fungi Rhizomucor miehei, Humicola lanuginosa, Rhizopus delemar and P. camembertii, have had their structures elucidated by X-ray crystallography. In spite of pronounced sequence similarities the enzymes exhibit significant differences. For example, the thermostability of the P. camembertii lipase is considerably lower than that of the H. lanuginosa enzyme. Since only the P. camembertii enzyme lacks the characteristic long disulfide bridge, corresponding to Cys22-Cys268 in the H. lanuginosa lipase, we have engineered this disulfide into the former enzyme in the hope of obtaining a significantly more stable fold. The properties of the double mutant (Y22C and G269C) were assessed by a variety of biophysical techniques. The extra disulfide link was found to increase the melting temperature of the protein from 51 to 63 degrees C. However, no difference is observed under reducing conditions, indicating an intrinsic instability of the new disulfide. The optimal temperature for catalytic activity decreased by 10 degrees C and the optimum pH was shifted by 0.7 units to more acidic.

Base Sequence↗

PubMed1996

Biological activity of analogues of YM022. Novel (3-amino substituted phenyl)urea derivatives of 1,4-benzodiazepin-2-one as gastrin/cholecystokinin-B receptor antagonists.

A series of (3-substituted phenyl)urea analogues of the potent gastrin/cholecystokinin (CCK)-B receptor antagonist YM022 has been prepared. Structure-activity relationship studies of this series suggested that a number of analogues retained good in vitro potency for gastrin/CCK-B receptor. In particular, the (3-amino substituted phenyl)urea derivatives (10-12) were more potent inhibitors of pentagastrin-induced gastric acid secretion in rats than YM022 on intraduodenal (i.d.) administration.

Animals↗

PubMed1996

Novel 5-hydroxytryptamine (5-HT3) receptor antagonists. IV. Synthesis and pharmacological evaluation of the oxidation products of (-)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl] -4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride (YM060: ramosetron).

In physicochemical and pharmacokinetic evaluations of (--)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl] -4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride 1 (YM060: ramosetron), which is a highly potent 5-hydroxytryptamine(-HT3) receptor antagonist, 4-hydroxy-6-[(1-methyl-1H-indol-3-yl) carbonyl]4,5,6,7-tetrahydro-1H-benzimidazole 2 was identified as a degradation product and metabolite of 1. The (--)-(4R,6S)-isomer 2 was synthesized from the diketone derivative 3, via the stereoselective reduction of 3 followed by the stereocontrolled epimerization of the (--)-(4S,6S)-isomer 10, the epimer of 2. The stereochemistry of 2 and 10 was determined by NMR and HPLC studies. Compounds 2 and 10 were found to be potent 5-HT3 receptor antagonists, like 1. Among the other oxidation products, the diketone derivatives 3 and 7 and the dihydroxylated derivative 4 retained antagonistic activity similar to that of ondansetron. This is of interest, because they do not possess the amine group which is known to be necessary for high affinity to the 5-HT3 receptor.

Animals↗

PubMed1996

[Immediate surgical treatment for the traumatic pulmonary pseudocyst: a case report].

Nonpenetrating blunt trauma causing pulmonary pseudocyst is very rare. A 25-year-old young male suffered from motor vehicle accident. He was transferred to our hospital with severe hemoptysis. Immediately he was intubated and kept under mechanical ventilation. A chest X-ray film and CT-scan revealed a marked cavity lesion surrounded by an extensive infiltrate and alveolar air consolidation. Ordinary, it has benign clinical courses by conservative management. However, he was suffered massive and continuous bleeding from endobronchial tube. Therefore, one lung ventilation using a uni-vent tube blocker was performed. After twelve hours blockade, the cavity lesion was enlarged and trans-bronchial bleeding was continued severely. Emergency right lower lobectomy was carried out successfully.

Accidents, Traffic↗

PubMed1996

[Successful second stage operations for bilateral giant bullae with cardiovascular disease by thoracotomy and thoracoscopic surgery: a case report].

A 65-year-old male was admitted to our hospital because of bilateral giant bullae and right side pneumothorax. He had had a myocardial infarction and had been receiving medications. Considering his age, ischemic heart disease and hypertension, we excised the bullae in two operations. The first operation was open chest bullectomy of a giant bulla and small bulla on the right side. After this procedure, his clinical course was uneventful. In the second operation, thoracoscopic excision of the left side giant bulla was performed using only one endoscopic stapler by rotating each side of the bulla and making a clear excision line between the bulla and normal lung. His post operative course was excellent and he was discharged from our hospital on the 15th day after the second operation.

Aged↗

PubMed1995

Structure-activity relationships of cyclic pentapeptide endothelin A receptor antagonists.

Analogues of the natural product endothelin A (ETA) receptor antagonists cyclo(-D-Trp1-D-Glu2-Ala3-D-Val4-Leu5-) (1) and cyclo(-D-Trp1-D-Glu2-Ala3-D-alloIle4-Leu5-) (2) were prepared and tested for inhibitory activity against [125I]endothelin (ET-1) binding to protein ETA receptors. The DDLDL chirality sequence of the natural products appeared to be critical for inhibitory activity because conversion of either D-Trp or D-Glu (or both) in 1 to the corresponding L-isomer(s) abolished this property. Systematic modifications at each position of the natural products clarified the structure-activity relationships and led to highly potent and selective ETA receptor antagonists. Most replacements of D-Trp1 and Leu5 with other amino acids caused a significant loss of inhibitory activity. In contrast, replacement of D-Glu2 with D-Asp2 enhanced the activity. With regard to the Ala3 position, all analogues with imino acids, independent of being cyclic or acyclic, showed higher affinities than did the amino acid analogues. In addition, most replacements with amino acids, which had various functional groups in their side chains, did not significantly modify ETA binding affinity. The D-Val4/D-alloIle4 position was very important for inhibitory activity, and a beta-position branched D-amino acid or a D-heteroarylglycine was preferable at this position. Among synthesized cyclic pentapeptides, compound 36 (BQ-518) was the most potent ETA receptor antagonist, with a pA2 of 8.1 against ET-1-induced vasoconstriction in isolated porcine coronary arteries. This compound also showed the greatest selectivity between ETA and ETB receptors (IC50 for human ETA = 1.2 nM, IC50 for human ETB = 55 microM). In contrast, compound 8 (BQ-123) is a highly soluble, potent, and selective ETA receptor antagonist (pA2 = 7.4, IC50 for human ETA = 8.3 nM, IC50 for human ETB = 61 microM). The sodium salt of 8 is practically freely soluble in saline. These compounds are useful tools for not only in vitro but also in vivo pharmacological studies.

Amino Acid Sequence↗

PubMed1995

New 1,4-benzodiazepin-2-one derivatives as gastrin/cholecystokinin-B antagonists.

A novel series of 1-aroylmethyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one derivatives was prepared and evaluated for activity as gastrin/cholecystokinin (CCK)-B receptor antagonists. In vitro binding studies showed that some derivatives exhibited potent affinity for gastrin CCK-B receptor and high selectivity over peripheral CCK(CCK-A) receptor. Furthermore these compounds potently inhibited pentagastrin-induced gastric acid secretion upon intravenous administration in an in vivo model in rats. Structure-activity relationship studies of this series suggested that 1-[(R)-2,3-dihydro-1-(2,3-dihydro-1-(2-methylphenacyl)-2-oxo-5-phe nyl-1H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (35b, YM022) was the optimal compound with IC50 values of 0.17, 0.11 and 150 nM for gastrin, CCK-B and CCK-A receptors, respectively, and an ED50 value of 9.5 nmol/kg (i.v.) in rats. The absolute configuration of the precursor of YM022, an (R)-3-amino-1,3-dihydro-2H-1,4-benzodiazepin-2-one derivative ((R)-25), was determined by X-ray crystallographic analysis of its (S) mandelate. It would be expected that YM022, a potent and selective gastrin CCK-B receptor antagonist, inhibits gastric acid secretion without inducing gastrin-mediated side effects such as hypergastrinemia and hyperplasia of oxyntic mucosa.

Anesthetics↗

PubMed1995

Purification and characterization of a new lipase from Fusarium sp. YM-30.

The extracellular lipase from Fusarium sp. YM-30 was purified by a procedure involving ultrafiltration, ammonium sulfate precipitation, and DEAE-Toyopearl 650M, CM-Toyopearl 650M, and Butyl-Toyopearl 650M column chromatographies. The purified lipase was homogeneous with 12kDa of molecular mass by SDS-PAGE, and had high specificities for mono- and diacylglycerols, but low toward triacylglycerols. The enzyme had maximum activity at pH 7.0 to 8.0 and 37 degrees C, and hydrolyzed digalactosyl diglyceride too.

Animals↗

PubMed1995

Antitumor effects of pirarubicin and epirubicin in combination with doxifluridine and cisplatin against mouse P388 leukemia.

In vivo antitumor activity of pirarubicin (THP) and epirubucin (EPI) in combination with doxifluridine (5'-DFUR) and cisplatin (CDDP) were examined using mouse P388 leukemia. THP (1.25-7.5 mg/kg) or EPI (1.25-15 mg/kg) was given intravenously on day 1, and then 5'-DFUR (125 or 250 mg/kg/day) and CDDP (4 mg/kg) were given orally on days 1-4 and intravenously on day 5 after tumor inoculation, respectively. Both THP and EPI enhanced the antitumor of a combination of 5'-DFUR and CDDP. The enhancement by THP was additive or synergistic, while that by EPI was additive. Cured animals were observed in the combination of THP with the two drugs, but not in that of EPI. Thus, in combination with 5'-DFUR and CDDP, THP was more effective against P388 leukemia than was EPI. The combination therapy using THP, 5'-DFUR and CDDP may be a novel chemotherapeutic approach to a variable type of tumors in clinical trials.

Animals↗

PubMed1995

Effects of cytogenin on spontaneous arthritis in MRL/1 mice and on pristane-induced arthritis (PIA) in DBA/1J mice.

Cytogenin, 8-hydroxy-3-hydroxymethyl-6-methoxyisocoumarin, has low cytotoxicity on murine and human tumour cells in vitro. It augments or suppresses phagocytosis of macrophages and lymphocyte proliferation. It has been reported that cytogenin has a potent inhibitory effect clinically on adjuvant arthritis in Lewis rats and on type II collagen-induced arthritis in DBA/1J mice. Our experimental findings provide evidence that cytogenin has beneficial effects on spontaneous polyarthritis in MRL/1 mice and pristane-induced arthritis in DBA/1J mice. The results suggest that the mode of the anti-arthritic action of cytogenin is different from those of NSAIDs; although the precise mode of action remains unclear, cytogenin may become an excellent therapeutic agent for rheumatoid arthritis.

Animals↗

PubMed1994

Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788.

We describe the characteristics of a potent and selective endothelin (ET) B-receptor antagonist, BQ-788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D -1- methoxycarbonyltryptophanyl-D-norleucine]. In vitro, this compound potently and competitively inhibits 125I-labeled endothelin 1 (ET-1) binding to ETB receptors on human Girardi heart cells (IC50, 1.2 nM) but only poorly inhibits the binding to ETA receptors on human neuroblastoma cell line SK-N-MC cells (IC50, 1300 nM). In isolated rabbit pulmonary arteries, BQ-788 shows no agonist activity up to 10 microM and competitively antagonizes the vasoconstriction induced by an ETB-selective agonist, BQ-3020 (pA2, 8.4). In rat, an ETA-selective antagonist, BQ-123 (1 mg/kg, i.v.), does not affect transient depressor response to ET-1 (0.3 nmol/kg, i.v.) but potently inhibits following sustained pressor response; vice versa, BQ-788 (1 mg/kg, i.v.) abolishes the depressor response, resulting in a rapid onset of apparently enhanced pressor response. Thus, being a potent and selective ETB receptor antagonist, BQ-788 may be considered as a powerful tool for investigating the role of ET in physiological and pathological processes.

Amino Acid Sequence↗

PubMed1994

Purification and characterization of an alkaline lipase from Pseudomonas fluorescens AK102.

An extracellular, novel alkaline lipase produced by Pseudomonas fluorescens AK102 was purified by ultrafiltration, ammonium sulfate precipitation, and DEAE-Toyopearl 650M and Phenyl-Toyopearl 650M column chromatographies. The purified enzyme was homogeneous on SDS-PAGE. The molecular weight was estimated to be about 33,000 by SDS-PAGE. The isoelectric point was pH 4.0 by isoelectric focusing. The pH stability was 4 to 10 and the optimum pH was 8 to 10. The optimum temperature was 55 degrees C and the enzyme was stable below 50 degrees C. The enzyme unspecifically liberated short chain to long chain fatty acids from p-nitrophenyl esters, methyl esters, and triglycerides. In the presence of an anionic surfactant, the enzyme was characteristically stable. These results suggested that the enzyme can be used as a home laundry product ingredient.

Amino Acid Sequence↗