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Biomedical subjects

T Kurihara

Publications and source records attributed to T Kurihara.

At least 181 records · Page 10Linked to original sources
PubMed1994

Comparative studies of genes encoding thermostable L-2-halo acid dehalogenase from Pseudomonas sp. strain YL, other dehalogenases, and two related hypothetical proteins from Escherichia coli.

We have determined the nucleotide sequence of the gene encoding thermostable L-2-halo acid dehalogenase (L-DEX) from the 2-chloroacrylate-utilizable bacterium Pseudomonas sp. strain YL. The open reading frame consists of 696 nucleotides corresponding to 232 amino acid residues. The protein molecular weight was estimated to be 26,179, which was in good agreement with the subunit molecular weight of the enzyme. The gene was efficiently expressed in the recombinant Escherichia coli cells: the amount of L-DEX corresponds to about 49% of the total soluble proteins. The predicted amino acid sequence showed a high level of similarity to those of L-DEXs from other bacterial strains and haloacetate dehalogenase H-2 from Moraxella sp. strain B (38 to 57% identity) but a very low level of similarity to those of haloacetate dehalogenase H-1 from Moraxella sp. strain B (10%) and haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 (12%). By searching the protein amino acid sequence database, we found two E. coli hypothetical proteins similar to the Pseudomonas sp. strain YL L-DEX (21 to 22%).

Amino Acid Sequence↗
PubMed1994

Evidence for deactivation of both ectosolic and cytosolic 5'-nucleotidase by adenosine A1 receptor activation in the rat cardiomyocytes.

Adenosine, an important regulator of many cardiac functions, is produced by ectosolic and cytosolic 5'-nucleotidase. The activity of these enzymes is influenced by several ischemia-sensitive metabolic factors, e.g., ATP, ADP, H+, and inorganic phosphate. However, there is no clear evidence that adenosine itself affects 5'-nucleotidase activity. This study tested whether adenosine decreases the activity of ectosolic and cytosolic 5'-nucleotidase. Cardiomyocytes were isolated from adult male Wistar rats and suspended in the modified Hepes-Tyrode buffer solution. After stabilization, isolated cardiomyocytes were incubated with and without adenosine (10(-9) - 10(-4) M). Ectosolic and cytosolic 5'-nucleotidase activity was decreased by exogenous adenosine (ectosolic 5'-nucleotidase activity, 20.6 +/- 2.3 vs. 8.6 +/- 1.6 mumol/min per 10(6) cells [P < 0.05]; cytosolic 5'-nucleotidase activity, 2.47 +/- 0.58 vs. 1.61 +/- 0.54 mumol/min per 10(6) cells [P < 0.05] at 10(-6) M adenosine) after 30 min. The decrease in ectosolic and cytosolic 5'-nucleotidase activity was inhibited by 8-phenyltheophylline and pertussis toxin, and was mimicked by N6-cyclohexyladenosine, an adenosine A1 receptor agonist. Neither CGS21680C, and A2 receptor agonist, nor cycloheximide deactivated ectosolic and cytosolic 5'-nucleotidase. Thus, we conclude that activation of adenosine A1 receptors is coupled to Gi proteins and attenuates ectosolic and cytosolic 5'-nucleotidase activity in rat cardiomyocytes.

5'-Nucleotidase↗
PubMed1994

Substituted 1,8-naphthyridin-2(1H)-ones as selective phosphodiesterase IV inhibitors.

New substituted 1,8-naphthyridin-2(1H)-ones have been found to exhibit highly selective phosphodiesterase (PDE) IV inhibition. These compounds inhibited polymorphonuclear leukocyte activation induced by N-formylmethionyl-leucyl-phenylalanine and caused relaxation of isolated guinea pig trachea precontracted by histamine or leukotriene D4. In anesthetized guinea pigs, presensitized with the antigen, these compounds also alleviated airway constriction induced by the antigen. Since these compounds differ in their chemical structure compared with theophylline and other PDE IV inhibitors so far reported and some of them have been shown to be well tolerated in acute toxicity studies, they will provide a new tool for investigating the possible relationship between PDE IV inhibition and anti-asthmatic activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Novel and potent aldose reductase inhibitors: 4-benzyl- and 4-(benzothiazol-2-ylmethyl)-3,4-dihydro-3-oxo-2H-1,4-benzothiazine-2-ac etic acid derivatives.

A number of 1,4-benzothiazine-2-acetic acid derivatives (1, 2 and 3) and their bioisosteres (15b, 16, 18 and 20b) were synthesized and evaluated in vitro for the ability to inhibit aldose reductase (AR) in porcine lens. The compounds which exhibited potent activity in vitro were also assayed in vivo for inhibitory activity against sorbitol accumulation in the erythrocytes, sciatic nerve and lens of streptozotocin-diabetic rats. The 4-(substituted benzothiazol-2-ylmethyl)-1,4-benzothiazine-2-acetic acid derivatives (2 and 3) showed more potent AR inhibitory activity than did the 4-(4-bromo-2-fluorobenzyl)-1,4-benzothiazine-2-acetic acid derivatives (1). 4-(4,5,7-Tri-fluorobenzothiazol-2-ylmethyl)-3,4-dihydro-3- oxo-2H-1,4-benzothiazine-2-acetic acid (2q, SPR-210) showed not only a potent AR-inhibitory activity in vitro (IC50 9.5 x 10(-9) M) but also a significant reduction in sorbitol accumulation in rat sciatic nerve (ID50 0.1 mg/kg) and lens (ID50 9.8 mg/kg). Optical resolution of the racemic SPR-210 was achieved by means of a diastereomer salt method using (-)-brucine. The biological activities of both enantiomers, (+)- and (-)-SPR-210, were comparable to that of the racemate.

Acetates↗
PubMed1994

Meisenheimer rearrangement of azetopyridoindoles, VI. Synthesis of 12-carbaeudistomin and related compounds.

For structure-activity relationship investigation of eudistomins 1, 12-carbaeudistomin 3, its 1,10-trans isomer 4, and 11,12-didehydro-12-carbaeudistomin 5 have been synthesized. The [2,3]-Meisenheimer rearrangement of the corresponding N-oxide of the 2-vinylazetopyridoindole 12a bearing a benzenesulfonyl group as a protective group of the indole nitrogen atom afforded the oxazepino ester 14, which was easily isomerized to 20a. Compounds 3 and 4 were synthesized from 14 and 20a, respectively, according to the following reaction sequences [hydrogenation of the double bond (Pd-C/H2), desulfonylation (Mg in MeOH), hydrolysis (AlBr3-EtSH), and Curtius rearrangement (a mixed anhydride method using NaN3), followed by debenzylation (Pd-C/H2)]. The Curtius reaction of the carboxylic acid 27 using DPPA gave the carbamate 29, which was subjected to debenzylation (AlBr3-EtSH) followed by desulfonylation (LiAlH4) to afford 5. Evaluation of anti-influenza virus activities of the amino compounds 3, 4, and 5 revealed that 12-carbaeudistomin 3 possesses a specific activity against influenza virus B.

Antiviral Agents↗
PubMed1994

[Unilateral external ophthalmoplegia caused by ipsilateral oculomotor nuclear lesion: analysis with diffusion weighted MRI].

A 49-year-old man who had been suffering from poorly controlled diabetes mellitus for 20 years was admitted to our hospital with the chief complaints of diplopia and right ptosis. The onset of his symptoms was sudden. On admission, he had right palpebral ptosis, upward and left lateral gaze paresis of the right eye. Hess screen chart examination revealed paresis of the right superior rectus, inferior oblique and medial rectus muscles. T2 weighted magnetic resonance imaging (MRI) revealed high intensity area in the medial part of the right midbrain tegmentum where the oculomotor nucleus located, and diffusion weighted MRI demonstrated high intensity area which corresponded to the oculomotor fascicles of the midbrain. The latter represented Wallerian degeneration of the fascicles. The diagnosis of small infarction of the right oculomotor nucleus presenting ipsilateral external ophthalmoplegia was made. The superior rectus muscle is innervated by the neurons in the contralateral oculomotor nucleus, and the other external ocular muscles innervated by the third cranial nerve are conducted by the neurons in the ipsilateral oculomotor nucleus; therefore, unilateral oculomotor nuclear lesion generally causes ipsilateral ophthalmoplegia plus contralateral superior rectus palsy. Our case presented here shows that there may be such a case with oculomotor nuclear disturbance which masquerades with oculomotor fascicular or infranuclear disturbance; therefore, it is important to include these lesions in differential diagnosis.

Cerebral Infarction↗
PubMed1994

[Is myocardial fatty acid metabolism different between hypertrophic cardiomyopathy and hypertensive hypertrophy?].

To investigate the characteristics of fatty acid metabolism in hypertrophic cardiomyopathy (HCM), we performed myocardial imaging with 123I-iodophenyl-3-methylpentadecanoic acid (BMIPP) in 24 patients with HCM, 13 patients with hypertensive hypertrophy (HT) and 10 normal subjects. Rest myocardial imaging with 123I-BMIPP was obtained at 20 minutes and 3 hours after 123I-BMIPP injection. Rest 201Tl imaging was also performed. In addition to ordinary tomography, whole body imaging was performed to calculate % Uptake (percentage of cardiac uptake of the isotope to total injected dose). As global indexes of fatty acid metabolism, we calculated two parameters; 1) Uptake Ratio (%Uptake of 123I-BMIPP normalized by myocardial perfusion) and 2) WOR (percent reduction of myocardial 123I-BMIPP within 3 hours). Regional abnormality was evaluated by visual assessment of ordinary tomograms and by BMIPP/T1 map. BMIPP/T1 map was made from Bull's-eye maps of 123I-BMIPP and 201Tl, and it represented 123I-BMIPP uptake normalized by myocardial perfusion of each pixel which constructed the image. %Uptake of 123I-BMIPP was not different among three groups. But Uptake Ratio was significantly (p < 0.001) different among three groups; normal (1.13 +/- 0.08) > HT (1.03 +/- 0.08) > HCM (0.87 +/- 0.09). WOR of 123I-BMIPP was accelerated in HCM (12.7 +/- 4.7%) and HT (10.2 +/- 2.9%) comparing with that in normal (5.1 +/- 3.1%) (p < 0.01). In patients with HCM, by visual assessment, regional abnormality of 123I-BMIPP distribution was found in 17 of 24 patients (71%) including 3 patients with equivocal abnormality. But in patients with HT, only equivocal abnormality was observed in 23%. In BMIPP/T1 map, abnormality was observed in 92% of HCM and 8% of HT. Although global myocardial fatty acid metabolism was equally disturbed both in HCM and HT, regional abnormality of fatty acid metabolism was observed preferentially in HCM. This indicated myocardial fatty acid metabolism was not identical between HCM and HT.

Adult↗
PubMed1994

[Myocardial imaging with 123I-metaiodobenzylguanidine (123I-MIBG) in essential hypertension: does the 123I-MIBG imaging have the ability to predict its prognosis?].

To study myocardial norepinephrine (NE) activity in essential Hypertension 9HT) and to clarify its prognostic significance, we performed myocardial imaging with 123I-metaiodobenzylguanidine (123I-MIBG) and 201Tl at rest in 16 patients with HT and 9 normal subjects. In addition to ordinary tomograms, whole body images were obtained in both 123I-MIBG and 201Tl imaging. From the whole body image, a ratio of myocardial radionuclide accumulation to total injected dose was calculated (%Uptake). And Uptake Ratio (%Uptake of 123I-MIBG/%Uptake of 201Tl) was used as an index of myocardial 123I-MIBG uptake. Reduction of myocardial 123I-MIBG during 3 hours was calculated and expressed as washout rate (WOR). From the Bull's-eye map, the extent of defect was quantitatively assessed (Defect Score) and the homogeneity of the radionuclide distribution within the myocardium (CV) was calculated. In 123I-MIBG imaging, defect appeared in 12 patients with HT (75%), but in normal subject no one showed defect. Patients with HT were divided into two groups according to left ventricular ejection fraction (EF) responses to exercise stress which were obtained by 99mTc blood pool imaging. Group 1 consisted of 8 patients who showed EF elevation (5-10%) by exercise and group 2 consisted of 6 patients with depression of EF (-4-6%) by exercise. Rest EF, peak filling rate, exercise heart rate, exercise blood pressure and left ventricular mass were identical between two groups. Uptake Ratio in Group 2 (0.67 +/- 0.04) was significantly smaller (p < 0.05) than those in Group 1 (0.75 +/- 0.05) and normal subject (0.75 +/- 0.06). And in Group 2, WOR of 123I-MIBG was greater than that of Group 1. In Group 2, defect of 123I-MIBG appeared in all patients, but in Group 1 defect developed in 50%, besides Defect Score was significantly greater in Group 2 than in Group 1 (3.8 +/- 1.4 vs. 1.5 +/- 1.8, p < 0.05). The unhomogeneity of 123I-MIBG distribution was significantly greater in Group 2 (CV; 30 +/- 5%) than in Group 1 (21 +/- 4%) and in normal subjects (18 +/- 4%). These results suggested that quantitative analysis of 123I-MIBG imaging may be helpful for assessing the prognosis of HT.

3-Iodobenzylguanidine↗
PubMed1994

[Quantitative evaluation of liver function with 99mTc-GSA scintigraphy using extraction index].

Extraction index (EI5) was introduced to evaluate liver function quantitatively with 99mTc-GSA (GSA) scintigraphy, and it was compared with conventional indices; receptor index (LHL15) and clearance index (HH15). EI5 is expressed as following equation: EI5 = (L5 - L3)/(H3 + H5) * PH/PL where L3, L5: counts at 3 or 5 minutes after the injection in the liver ROI, respectively, H3, H5: counts at 3 or 5 minutes in the heart ROI, respectively; PL, PH: numbers of pixels in the liver- and heart-ROI, respectively. We performed GSA scintigraphy in 40 patients with liver dysfunction and calculated values of the indices. Good correlations were observed between EI5 and liver function tests. Correlation coefficients were almost equal to or higher than those between conventional parameters and liver functional tests. EI5 was thought to be a practical index, and it could be calculated in a short time without aid of computer. Evaluation of local liver function may be possible, because EI5 was corrected with numbers of pixels in the liver- and heart-ROI; which was not considered in the conventional parameters.

Adult↗
PubMed1994

[Quantitative analysis of 123I-metaiodobenzylguanidine myocardial imaging: assessment of its usefulness in patients with congestive heart failure].

To investigate the usefulness of the quantitative analysis of 123I-metaiodobenzylguanidine (123I-MIBG) myocardial uptake, we studied 9 normal subjects and 18 patients with congestive heart failure (CHF). Rest myocardial imaging with 123I-MIBG was performed at 20 minutes and 3 hours (delayed image) after 123I-MIBG injection. Rest 201Tl imaging was obtained at 20 minutes after 201Tl injection. In addition to ordinary tomograms, a planar anterior image and a whole body image were supplemented in each imaging. In patients with CHF fractional shortening (%FS) was calculated from echocardiography and left ventricular ejection fraction was obtained from cardiac blood pool imaging with 99mTc at rest. We calculated H/M (heart to mediastinum count ratio) from the anterior planar image and %Uptake (percentage of cardiac uptake of the isotope to total injected dose) from the whole body image. H/M of 123I-MIBG in delayed images separated patients with CHF from normal subjects (2.00 +/- 0.19 vs. 2.56 +/- 0.13, p < 0.01). H/M Ratio (H/M of 123I-MIBG divided by H/M of 201Tl) in delayed image could distinguish these two groups poorly (0.72 +/- 0.12 vs. 0.88 +/- 0.14, p < 0.05). On the other hand, %Uptake of 123I-MIBG was not different between two groups (3.49 +/- 0.60% in CHF, 3.54 +/- 0.34% in normal). But %Uptake of 201Tl was greater in CHF than in normal (5.96 +/- 1.09% vs. 4.70 +/- 0.30%, p < 0.05). When myocardial 123I-MIBG uptake was normalized by myocardial perfusion (%Uptake of 123I-MIBG divided by %Uptake of 201Tl, Uptake Ratio), Uptake Ratio in delayed image could distinguish theses two groups as same as H/M (0.60 +/- 0.05 in CHF, 0.75 +/- 0.05 in normal, p < 0.01). In patients with CHF, H/M of 123I-MIBG did not reflect LV function and serum norepinephrine (NE) level. But Uptake Ratio and H/M Ratio in delayed image correlated well with %FS (r = 0.88, r = 0.65), EF (r = 0.80, r = 0.68) and NE level (r = -0.77, r = -0.75). Although the calculation of Uptake Ratio is time consuming and expensive, it was assumed that Uptake Ratio is an useful index to quantitate myocardial 123I-MIBG uptake.

3-Iodobenzylguanidine↗
PubMed1993

Structure, expression and chromosomal localization of the gene encoding human 2',3'-cyclic-nucleotide 3'-phosphodiesterase.

Four human genomic DNA clones for 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) were isolated by screening a human genomic library with human CNP cDNA clones as probes. Restriction mapping and sequence analysis revealed that the human CNP gene is about 8.5 kb long and composed of four exons interrupted by three introns. There are two transcription start points and in human brain, two forms of CNP mRNA are produced from a single gene by alternative splicing, similar to mouse. A homology search of the 5'-flanking regions of exon 0 and exon 1 in the human CNP gene indicated the presence of oligodendroglia-specific elements and myelin basic protein transcription element (MBTE) motif, in addition to TATA-box-like sequences. Spot blot hybridization of flow-sorted human chromosomes with the 3'-noncoding region of the human CNP cDNA showed the localization of CNP to chromosome 17.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1993

Murine bone morphogenetic protein-4 gene: existence of multiple promoters and exons for the 5'-untranslated region.

A murine genomic clone of about 16 kilobases encompassing putatively entire bone morphogenetic protein (BMP)-4 gene has been isolated. Comparison with the cDNA clones revealed the existence of at least five exons on the 3' side of the clone. There are two alternative transcriptional start sites, one is for the first exon the other for the second, the resulting exon organization in mRNA is I-III-IV-V and II-III-IV-V, respectively. The coding region is dispersed between exons IV and V. Both promoter regions carry no canonical TATA box but carry GC rich sequences.

Amino Acid Sequence↗
PubMed1993

Movement of intrapancreatic calcium in dogs with experimental pancreatic lithiasis. With special reference to the process of pancreatic calculus formation.

This study was performed to clarify the movement of calcium in the pancreas of dogs with chronic pancreatitis, using scanning and transmission electron microscopes (SEM, TEM) equipped with X-ray elemental microanalyzers. Eleven adult mongrel dogs underwent incomplete ligation of the pancreatic duct. After the procedure, the levels of pancreatic enzymes in the serum did not change for 9 mo, but the endocrine function was reduced gradually. Of all dogs, 5 revealed pancreatic sclerosis, and 2 at 9 mo had calculi, 2-4 mm in size, in the small pancreatic duct. SEM examination revealed the intralobular fibrosis and irregularity of the pancreatic duct wall, and TEM examination revealed the intralobular fibrosis and irregularity of the pancreatic duct wall, and TEM examination demonstrated the amorphous or crystalloid substances and secreted granules in the acinar lumen or ductule. In elemental analysis spectra using SEM, a high calcium peak was seen in the pancreatic duct wall. In elemental analysis spectra using TEM, a high calcium peak was observed in the amorphous or crystalloid substances, and a high ratio of Ca/K was seen in these substances. Calcium was also detected in the secreted granules or microvilli. These results suggest that there is a process of calculus formation based on the congregation of the intraductular substances containing a large quantity of calcium.

Animals↗
PubMed1993

Neuropsychological function before and after plasma exchange in myasthenia gravis.

This study was designed to determine whether there are cognitive and memory impairments in patients with myasthenia gravis (MG). Five female patients with MG were tested on two occasions, 4-6 days apart, prior to plasma exchange and after plasma exchange. All subjects had 2-4 separate plasma exchanges. The subjects were tested with mini-mental state examination (MMS), Zung self-rating depression scale (SDS) and a logical memory test. The MG group was significantly impaired compared to the control group on all tests prior to plasma exchange. The MG patients improved in motor function with plasma exchange. In addition, the mean MMS score improved from 26.4 to 28.2 and the mean SDS score improved from 0.46 to 0.39 and the mean immediate logical memory score improved from 5.8 to 8.4 and mean delayed logical memory score improved from 5.8 to 8.0. These improvements were all significant (P < 0.05). The results support the hypothesis that MG has central cholinergic effects, manifested by cognitive dysfunction.

Adult↗
PubMed1993

Effects of treatment with methyl methanesulfonate during meiotic and postmeiotic stages and maturation of spermatozoa in mice.

DNA damage and its related effects were quantitatively measured in germ cells at various meiotic and postmeiotic stages in male mice treated with methyl methanesulfonate (MMS). Unscheduled DNA synthesis (UDS) took place most efficiently in germ cell stages from middle to late spermatocytes at the time of MMS treatment, and essentially no UDS was detected in the stages from late spermatid to maturing spermatozoa, suggesting the absence of DNA repair in late spermatids and maturing spermatozoa. Late spermatids and immature spermatozoa were, on the other hand, most sensitive to MMS in producing DNA single-strand breaks (SSB) as well as chromosome aberrations in eggs fertilized by the treated males. The storage of the spermatozoa in the reproductive tract appeared to enhance the production of SSB. DNA damages induced by MMS should cause various genetic effects during the postmeiotic stages and maturation of spermatozoa through mechanisms not related to excision repair.

Animals↗