Biomedical subjects

M Takeuchi

Publications and source records attributed to M Takeuchi.

At least 325 records · Page 18Linked to original sources

PubMed1998

Thumb reconstruction, after Marjolin's ulcer resection by microvascular transfer of a burn-contracted little finger: a case report of spare part surgery.

Thumb reconstruction after amputation due to a squamous cell carcinoma in a burn scar sustained in infancy was accomplished by microvascular transfer of the ipsilateral scar-contracted little finger. This transfer achieved a successful functional and aesthetic thumb reconstruction and at the same time removed a 'cumbersome' little finger which had often snagged on things. This case emphasises the merits of unused part transfer in hand reconstructive surgery, made possible by microvascular techniques.

Aged↗

PubMed1998

Structural determination of metabolites of S-1153, a new, potent, non-nucleoside, anti-HIV agent in rat liver microsomes.

1. S-1153, a non-nucleoside agent that is under development in the USA as a new anti-HIV agent, has potent antiviral activity based on the inhibition of reverse transcriptase. 2. S-1153 was incubated with rat liver microsomes and NADPH, and seven metabolites were formed. The main metabolites were identified as the S-oxide, N-oxide and sulphone of S-1153. 3. Two other minor metabolites were assumed to be S-1153 hydroxylated on the isopropyl moiety. 4. Our findings confirmed the existence of at least three oxidative metabolic pathways of S-1153.

Animals↗

PubMed1998

Pharmacokinetics of a novel benzodiazepine partial inverse agonist in the F344 rat, SD rat and B6C3F1 mouse.

1. The pharmacokinetics of a novel benzodiazepine partial inverse agonist (S-8510) were studied in the Fischer 344 (F344) rat and B6C3F1 mouse to obtain information for the planning of carcinogenicity studies. Sprague-Dawley (SD) rats were also included for comparison. 2. Clear non-linear elimination of S-8510 was observed after single oral administration of S-8510 in all animals tested (F344 rat, 1-50 mg/kg; SD rat and B6C3F1 mouse, 1-150 mg/kg). 3. Exposure of S-8510 after single oral administration was in the order F344 rat > B6C3F1 mouse > SD rat. 4. Multiple oral administration to F344 rat and B6C3F1 mouse decreased the exposure to S-8510. 5. These results indicate that it is very important to evaluate pharmacological and toxicological studies based on exposure and to be careful in selecting the species and strains of animal used in toxicology studies.

Administration, Oral↗

PubMed1998

Isolation of a tobacco cDNA encoding Sar1 GTPase and analysis of its dominant mutations in vesicular traffic using a yeast complementation system.

The cDNA clone of NtSAR1, a gene encoding the small GTPase Sar1p which is essential for vesicle formation from the endoplasmic reticulum (ER) membrane in yeast, has been isolated from Nicotiana tabacum BY-2 cells. NtSAR1 as well as AtSAR1 cDNA isolated from Arabidopsis thaliana [d'Enfert et al. (1992) EMBO J. 11: 4205] could complement the lethality of the disruption of SAR1 in yeast cells in a temperature-sensitive fashion. They also suppressed yeast sec12 and sec16 temperature-sensitive mutations as yeast SAR1 does. Using this complementation system, we analyzed the phenotypes of several mutations in plant SAR1 cDNAs in yeast cells. The expression of NtSAR1 H74L and AtSAR1 N129I showed dominant negative effect in growth over the wild-type SAR1, which was accompanied by the arrest of ER-to-Golgi transport. Such dominant mutations will be useful to analyze the role of membrane trafficking in plant cells, if their expression can be regulated conditionally.

Amino Acid Sequence↗

PubMed1998

Endoscope-assisted nasal osteotomy: a preliminary report.

We report the use of an endoscope-assisted technique for nasal osteotomy in 7 patients. The endoscopic approach has been especially helpful in performing the osteotomy safely and accurately, compensating for the drawbacks of the conventional blind osteotomy procedure. This form of surgery took only approximately 20 minutes longer than conventional surgery. We encountered no complications attributable to the endoscopic approach.

Adolescent↗

PubMed1998

Union of the genera Microbacterium Orla-Jensen and Aureobacterium Collins et al. in a redefined genus Microbacterium.

The 16S rRNA gene sequences of 19 strains, 11 strains representing validated Aureobacterium or Microbacterium species and eight strains of non-valid species or isolates, were determined. These sequences were aligned with the sequences of other validated Aureobacterium and Microbacterium species and related actinobacteria. A comparative sequence analysis of 43 strains revealed that the species of the genera Aureobacterium and Microbacterium form a monophyletic association in which species of both genera are intermixed. The high similarity in phylogenetic properties found in the species within both genera and the close relationship in physiological and chemotaxonomic features other than the diamino acid in the cell wall, provided strong evidence that the genera Aureobacterium and Microbacterium should be unified. An emended genus Microbacterium is proposed for the two combined genera. The following validated Aureobacterium species were combined to the genus Microbacterium: Aureobacterium arabinogalactanolyticum to Microbacterium arabinogalactanolyticum, Aureobacterium barkeri to Microbacterium barkeri, Aureobacterium esteraromaticum to Microbacterium esteraromaticum, Aureobacterium flavescens to Microbacterium flavescens, Aureobacterium keratanolyticum to Microbacterium liquefaciens, Aureobacterium luteolum to Microbacterium luteolum, Aureobacterium saperdae to Microbacterium saperdae, Aureobacterium schleiferi to Microbacterium schleiferi, Aureobacterium terrae to Microbacterium terrae, Aureobacterium terregens to Microbacterium terregens, Aureobacterium testaceum to Microbacterium testaceum, and Aureobacterium trichothecenolyticum to Microbacterium trichothecenolyticum.

Actinomycetales↗

PubMed1998

Gordonia rhizosphera sp. nov. isolated from the mangrove rhizosphere.

The taxonomic position of bacterial strain 141T, isolated from the mangrove rhizosphere, has been clarified by phenotypic, chemotaxonomic and phylogenetic studies. The strain possesses wall chemotype IV, MK-9(H2) as the predominant menaquinone, relatively long-chain mycolic acids (56-64) carbon atoms) and straight-chain saturated and monounsaturated fatty acids with a small amount of tuberculostearic acid. The G+C content of the DNA is 66.8 mol%. Similarity values for genes encoding 16S rRNA indicated that strain 141T represents a new species within the genus Gordonia for which the name Gordonia rhizosphera sp. nov. is proposed. The type strain of G. rhizosphere is 141T (IFO 16068T).

Actinomycetales↗

PubMed1998

Proposal of six new species in the genus Microbacterium and transfer of Flavobacterium marinotypicum ZoBell and Upham to the genus Microbacterium as Microbacterium maritypicum comb. nov.

Reference strains, including two mis-named organisms, 'Chromobacterium chocolatum' and Flavobacterium marinotypicum, isolates from soil and clinical specimens, all previously recognized as Aureobacterium or Microbacterium, were characterized taxonomically. On the basis of morphological, physiological and chemotaxonomic characteristics, as well as DNA-DNA hybridization data, six new species and one new combination are proposed in the genus Microbacterium: Microbacterium ketosireducens sp. nov. (type strain IFO 14548T), Microbacterium chocolatum sp. nov. (type strain IFO 3758T), Microbacterium aurantiacum sp. nov. (type strain IFO 15234T), Microbacterium hominis sp. nov. (type strain IFO 15708T), Microbacterium thalassium sp. nov. (type strain IFO 16060T), Microbacterium halophilum sp. nov. (type strain IFO 16062T) and Microbacterium maritypicum comb. nov. (type strain IFO 15779T).

Actinomycetales↗

PubMed1998

Renal tubular apoptosis after release of ureteral obstruction in the rat kidney.

BACKGROUND: Information concerning the mechanisms underlying recovery from hydronephrosis is limited. The frequency of apoptosis during healing from hydronephrosis was studied using a rat kidney model. METHODS: The presence of apoptosis was studied using an in situ DNA 3' end labeling method, electron microscopy, and agarose gel electrophoresis. RESULTS: The degree of apoptosis in both the medulla and cortex gradually increased during ureteral obstruction as shown by in situ DNA 3' end labeling. Release of the ureteral obstruction resulted in a further increase in the degree of apoptosis in the medulla and cortex. The increase in apoptosis in the medulla was transient and lasted for only 4 days following release, while that in the cortex continued for at least 3 weeks. Apoptosis in the glomerulus was not observed. Electron microscopy revealed cells with aggregated chromatin in compact granular masses that abutted the nuclear membrane. Following release of ureteral obstruction, DNA fragmentation characteristic of apoptosis was visible on agarose gel electrophoresis. CONCLUSION: These results suggest that apoptosis is involved in post-obstructive tubular damage in the rat kidney.

Animals↗

PubMed1998

Effect of atrioventricular sequential pacing on left ventricular flow dynamics in a patient with mid-ventricular obstruction.

The effect of dual chamber atrioventricular sequential pacing on the intraventricular pressure gradient was tested using Doppler echocardiography in a patient with hypertrophic mid-ventricular obstruction. Atrioventricular sequential pacing with relatively short atrioventricular delays reduced in the left ventricular pressure gradient at the mid-ventricular level. Also, atrioventricular sequential pacing affected the degree and profile of the isovolumetric relaxation flow. These results suggest that atrioventricular sequential pacing affects both systolic and diastolic left ventricular flow dynamics in mid-ventricular obstruction.

Cardiac Pacing, Artificial↗

PubMed1998

A study of sports-related mandibular angle fracture: relation to the position of the third molars.

Mandibular angle fractures have been considered attributable to the presence of unerupted third molars. We examined the relationship between the incidence of sports-related mandibular angle fractures and the presence of a mandibular third molar with emphasis on the position of the third molar. The incidence of angle fracture was significantly higher in the sports-related injury group than in the group with fracture due to other causes (P < 0.05). The incidence of angle fracture in the athletes with higher impaction scores was significantly higher than that in the subjects with higher scores who did not have sports-related fractures (P < 0.05). The percentage of rugby athletes with third molars was significantly higher than that of those without third molars (P < 0.001), and a high proportion of young athletes (89.5%) was considered to belong to a potential high-risk group for angle fractures. Our findings suggest that mandibular angle fractures are influenced by the presence and characteristics of the third molar in sports-related injuries.

Accidents, Traffic↗

PubMed1998

Serum thyroglobulin autoantibodies: prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma.

The prevalence of circulating thyroid autoantibodies (TgAb or antithyroid peroxidase) was increased nearly 3-fold in patients with differentiated thyroid cancers (DTC) compared with the general population (40% vs. 14%, respectively). Serum TgAb (with or without antithyroid peroxidase) was present in 25% of DTC patients and 10% of the general population. Serial postsurgical serum TgAb and serum Tg patterns correlated with the presence or absence of disease. Measurements of serum Tg were made in 87 TgAb-positive sera by a RIA and two immunometric assay (IMA) methods to study TgAb interference. TgAb interference, defined as a significant intermethod discordance (>41.7% coefficient of variation) between the Tg RIA and Tg IMA values relative to TgAb-negative sera, was found in 69% of the TgAb-positive sera. TgAb interference was characterized by higher Tg RIA vs. IMA values and was, in general, more frequent and severe in sera containing high TgAb concentrations. However, some sera displayed marked interference when serum TgAb was low (1-2 IU/mL), whereas other sera with very high TgAb values (>1000 IU/mL) displayed no interference. An agglutination method was found to be too insensitive to detect low TgAb concentrations (1-10 IU/mL) causing interference. Exogenous Tg recovery tests were an unreliable means for detecting TgAb interference. Specifically, the exogenous Tg recovered varied with the type and amount of Tg added and the duration of incubation employed. Further, recoveries of more than 80% were found for some sera displaying gross serum RIA/IMA discordances. The measurement of serum Tg in DTC patients with circulating TgAb is currently problematic. It is important to use a Tg method that provides measurements that are concordant with tumor status. IMA methods are prone to underestimate serum when TgAb is present, increasing the risk that persistent or metastatic DTC will be missed. The RIA method used in this study provided more clinically appropriate serum Tg values in the group of TgAb-positive patients with metastatic DTC. Furthermore, as serial serum TgAb measurements paralleled serial serum Tg RIA measurements, TgAb concentrations may be an additional clinically useful tumor marker parameter for following TgAb-positive patients. Disparities between serial serum Tg and TgAb measurements might alert the physician to the possibility of TgAb interference with the serum Tg measurement and prompt a more cautious use of such data for clinical decision-making.

Adolescent↗

PubMed1998

Selective muscarinic antagonists. I. Synthesis and antimuscarinic properties of 4-piperidyl benzhydrylcarbamate derivatives.

A series of 1-substituted-4-piperidyl benzhydrylcarbamate derivatives were synthesized and evaluated for binding affinity to M1, M2 and M3 receptors, and for antimuscarinic activities. Receptor binding assays indicated that 1-benzyl-4-piperidyl benzhydrylcarbamate derivatives showed higher affinities for M1 and M3 receptors, and good selectivities for M3 over M2 receptor, than the corresponding ester analog. These results indicate that the urethane bond is a novel linker for muscarinic antagonists, and serves to lock the molecular conformation and allows the hydrophobic portion and cationic site of the molecule to bind to M1 and M3 muscarinic receptors. Among the prepared compounds, 1-(4-methylaminobenzyl)-4-piperidyl benzhydrylcarbamate monohydrochloride (18b, YM-58790) exhibited potent inhibitory activity on bladder pressure in reflexly-evoked rhythmic contraction, comparable to oxybutynin and was approximately ten times less inhibitory on oxotremorine-induced salivary secretion than oxybutynin in rats. Further evaluation of antimuscarinic effects on bradycardia and pressor in pithed rats, and on tremor in mice, demonstrated that YM-58790 can be useful for treatment of urinary urge incontinence as a bladder-selective M3 antagonist with fewer side effects.

Animals↗

PubMed1998

Selective muscarinic antagonists. II. Synthesis and antimuscarinic properties of biphenylylcarbamate derivatives.

A novel series of biphenylylcarbamate derivatives were synthesized and evaluated for binding to M1, M2 and M3 receptors and for antimuscarinic activities. Receptor binding assays indicated that biphenyl-2-ylcarbamate derivatives had high affinities for M1 and M3 receptors and good selectivities for M3 receptor over M2 receptor, indicating that the biphenyl-2-yl group is a novel hydrophobic replacement for the benzhydryl group in the muscarinic antagonist field. In this series, quinuclidin-4-yl biphenyl-2-ylcarbamate monohydrochloride (8l, YM-46303) exhibited the highest affinities for M1 and M3 receptors, and selectivity for M3 over M2 receptor. Compared to oxybutynin, YM-46303 showed approximately ten times higher inhibitory activity on bladder pressure in reflexly-evoked rhythmic contraction, and about 5-fold greater selectivity for urinary bladder contraction against salivary secretion in rats. Moreover, selective antagonistic activity was also observed in vitro. Further evaluation of antimuscarinic effects on bradycardia and pressor in pithed rats, and on tremor in mice, showed that YM-46303 can be useful for the treatment of urinary urge incontinence as a bladder-selective M3 antagonist with potent activities and fewer side effects.

Animals↗

PubMed1998

2-(3-Pyridyl)thiazolidine-4-carboxamide derivatives. II. Structure-activity relationships and active configuration of 2-(3-pyridyl)thiazolidine-4-carboxamides as platelet-activating factor receptor antagonists.

Conversion of the 2-(3-pyridyl)thiazolidine part of 1-(3-phenylpropyl)-4-[2-(3-pyridyl)thiazolidine-4-carbonyl]piperazine (YM461), which is a potent platelet-activating factor (PAF) antagonist, to other rings was performed, and PAF antagonistic activities evaluated. The 2-(3-pyridyl)thiazolidine skeleton, which exists as a mixture of cis and trans diastereomers, played an important role in the potency of PAF antagonism. In this study, new effective skeletons were not uncovered, however, 2-(4-pyridyl)thiazolidine-4-carboxamides (1n and 1z) showed potent PAF antagonistic activities equal to the 3-pyridyl derivatives. From the results obtained for 1a, 1a(S), 1g and 1i, a cis-(2R,4R)-2-(3-pyridyl)thiazolidine-4-carboxamide was assumed to be the active configuration for PAF antagonism.

Animals↗

PubMed1998

Spiro-substituted piperidines as neurokinin receptor antagonists. III. Synthesis of (+/-)-N-[2-(3,4-dichlorophenyl)-4-(spiro-substituted piperidin-1'-yl)butyl]-N-methylbenzamides and evaluation of NK1-NK2 dual antagonistic activities.

To discover a novel NK1-NK2 dual antagonist, we have synthesized a series of spiro-substituted piperidines utilizing YM-35375 as a lead compound, and evaluated affinities for NK1 and NK2 receptors. In the N-methylbenzamide moiety, introduction of methoxy groups increased affinity for the NK1 receptor without a significant loss of affinity for the NK2 receptor. We also found that a conformation in which the phenyl groups of the N-methylbenzamide and 3,4-dichlorophenyl moieties are close to each other through a cis-amide bond, may be favorable for showing high affinity for the NK1 receptor and that a hydrogen bond-accepting group in the spiro-substituted piperidine moiety may be crucial for exhibiting high affinity for the NK2 receptor. Among the compounds prepared, YM-44778 (31) showed high and well-balanced affinity for NK1 and NK2 receptors (IC50 values of 18 and 16 nM, respectively). This compound also exhibited potent antagonistic activities against both NK1 and NK2 receptors (IC50 values of 82 and 62 nM, respectively) in isolated tissues.

Animals↗

PubMed1998

Studies on novel bone resorption inhibitors. II. Synthesis and pharmacological activities of fused aza-heteroarylbisphosphonate derivatives.

Two new series of fused aza-heteroarylbisphosphonates (5, 8), which are structurally quite different from incadronate (YM175), and related compounds were synthesized and evaluated for antiresorptive activity using a parathyroid hormone(PTH)-induced hypercalcemia model in rats (PIH model). Among these compounds, several exhibited more potent antiresorptive activity than pamidronate. In particular, [1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethylidene]bisphosphonic acid (5b, minodronate) was 100-fold more potent than pamidronate in not only the PIH model, but also in an immobilization bone atrophy model in rats (DA model), and was selected for clinical development. The structure-activity relationships in these new series of bisphosphonates are discussed.

Animals↗

PubMed1998

Spiro-substituted piperidines as neurokinin receptor antagonists. II. Syntheses and NK2 receptor-antagonistic activities of N-[2-aryl-4-(spiro-substituted piperidin-1'-yl)butyl]carboxamides.

In the course of our research on spiro-compounds as neurokinin receptor antagonists, N-[2-aryl-4-(spiro-substituted piperidin-1'-yl)butyl]carboxamides were designed, based on YM-35375 (3) as a lead compound, and evaluated for NK2 receptor-antagonistic activities. Some derivatives inhibited the binding of radio-labeled neurokinin A to the NK2 receptor with IC50 values at the level of 10(-9) M. Among these compounds, (+/-)-1'-[4-(N-benzoyl-N-methylamino)-3- (3,4-dichlorophenyl)butyl]spiro[benzo[c]thiophene-1(3H), 4'-piperidine] 2-oxide (58, YM-38336) showed 10 times more potent NK2 receptor binding affinity than compound 3 (IC50 values of 8.9 and 84 nM, respectively). It showed more potent inhibitory activity (ID50 20 micrograms/kg (i.v.)) against [beta-Ala8]-NKA(4-10)-induced bronchoconstriction in guinea pigs than compound 3 (ID50 41 micrograms/kg (i.v.)). This compound was also effective intraduodenally in the same model, exhibiting an ID50 value of 0.41 microgram/kg.

Amides↗