Search PubMed⌕ Search

Biomedical subjects

T Ishikawa

Publications and source records attributed to T Ishikawa.

At least 199 records · Page 11Linked to original sources
PubMed2001

Inactivation of rat cytochrome P450 2D enzyme by a further metabolite of 4-hydroxypropranolol, the major and active metabolite of propranolol.

Repetitive administration of propranolol (PL) in rats decreases the activities of cytochrome P450 (CYP) 2D enzyme(s) in hepatic microsomes. We examined the properties of 4-hydroxypropranolol (4-OH-PL) as an inactivator of rat liver microsomal CYP2D enzyme(s) using bunitrolol (BTL) 4-hydroxylation and PL 5- and 7-hydroxylations as indices of CYP2D enzyme activity. Rat microsomal BTL 4-hydroxylase activity was inhibited by the addition of 4-OH-PL to the incubation medium. The inhibition was greater after preincubation of microsomes with 4-OH-PL in the presence of NADPH than in its absence. The type of inhibition kinetics of BTL 4-hydroxylase by 4-OH-PL was changed from a competitive type to a noncompetitive type by the preincubation. The inhibition of rat liver microsomal PL 5- and 7-hydroxylases by 4-OH-PL was blocked efficiently by co-incubation with quinine, a typical inhibitor of rat CYP2D enzyme(s), or to a lesser extent by BTL. However, quinidine, a diastereomer of quinine, did not significantly protect against the enzyme inactivation. The protective capacities of the substrate and inhibitors reflected their affinities for rat CYP2D enzyme(s). BTL hydroxylase was not affected by either 1,4-naphthoquinone or 1,4-dihydroxynaphthalene which are possible metabolites of 4-OH-PL. These results provide further evidence to support the notion that PL is biotransformed by rat CYP2D enzyme(s) to 4-OH-PL, which is further oxidized to a chemically reactive metabolite in the active site. The inactivation of CYP is likely the result of covalent binding of the reactive species to an amino acid residue of the active site.

Adrenergic beta-Antagonists↗
PubMed2001

The practical synthesis of a uterine relaxant, bis(2-[[(2S)-2-([(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl]amino)-1,2,3,4-tetrahydronaphthalen-7-yl]oxy]-N,N-dimethylacetamide) sulfate (KUR-1246).

The synthetic route for a uterine relaxant, bis(2-[[(2S)-2-([(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl]amino)-1,2,3,4-tetrahydronaphthalen-7-yl]oxy]-N,N-dimethylacetamide) sulfate (KUR-1246), was established by the coupling of optically active components, the bromohydrin 14 and the amine 24. We now describe the practical synthesis of these two optically active components. Bromohydrin 14 was obtained by the asymmetric borane reduction of the prochiral phenacyl bromide 13 using a catalyst prepared from aluminum triethoxide and a chiral amino alcohol. The other optically active component 24 was prepared from (S)-AMT.

Acetamides↗
PubMed2001

Preparation of rapidly disintegrating tablet using new types of microcrystalline cellulose (PH-M series) and low substituted-hydroxypropylcellulose or spherical sugar granules by direct compression method.

To decrease the sensation of roughness when a tablet, which is rapidly disintegrated by saliva (rapidly disintegrating tablet), is orally taken, we prepared rapidly disintegrating tablets using microcrystalline cellulose (Avicel PH-M series), a new type of pharmaceutical excipient that is spherical and has a very small particle size (particle size, 7-32 microm), instead of conventional microcrystalline cellulose (PH-102) used in the formulation of tablets containing acetaminophen or ascorbic acid as model drugs for tableting study. Tablets (200 mg) prepared using spherical microcrystalline cellulose, PH-M-06, with the smallest particle size (mean value, 7 microm) had sufficient crushing tolerance (approximately, 8 kg) and were very rapidly, disintegrated (within 15 s) when the mixing ratio of PH-M-06 to low-substituted hydroxypropylcellulose (L-HPC) was 9:1. Sensory evaluation by volunteers showed that PH-M-06 was superior to PH-102 in terms of the feeling of roughness in the mouth. Consequently, it was found that particle size is an important factor for tablet preparation using microcrystalline cellulose. It is possible to prepare drugs such as acetaminophen and ascorbic acid (concentration of approximately 50%) in the tablet form using PH-NM-06 in combination with L-HPC as a good disintegrant at a low compression force (1-6 kN). To solve the problem of poor fluidity in the preparation of these tablets, we investigated the use of spherical sugar granules (Nonpareil, NP-101 (sucrose and starch, composition ratio of 7:3), NP-103 (purified sucrose), NP-107 (purified lactose) and NP-108 (purified D-mannitol)). Rapidly disintegrating tablets can be prepared by the direct compression method when suitable excipients such as fine microcrystalline cellulose (PH-M-06) and spherical sugar granules (NP) are used.

Carbohydrates↗
PubMed2001

Pharmacokinetics of acetaminophen from rapidly disintegrating compressed tablet prepared using microcrystalline cellulose (PH-M-06) and spherical sugar granules.

The aim of the present study was to evaluate the bioavailability of a drug from rapidly disintegrating tablets prepared using fine spherical crystalline cellulose (PH-M-06) and spherical sugar granules (Nonpareil, NP). Rapidly disintegrating tablets containing acetaminophen as the model drug in combination with a mixture of NP-108 (purified n-mannitol) and PH-M-06 were prepared. Plasma concentration profiles and pharmacokinetic parameters of acetaminophen in rabbits were investigated after oral administration of the prepared tablets. No significant difference in Cmax and AUC(0-infinity) of acetaminophen between rapidly disintegrating tablets and conventional tablets was observed after direct administration of these tablets into the stomach of rabbits. However, tmax (15 min) of acetaminophen from rapidly disintegrating tablets was significantly (p<0.05) shorter than that from conventional tablets (130 min). The same tmax was observed for rapidly disintegrating tablets and solution. When suitable excipients such as fine spherical microcrystalline cellulose (PH-M series) and spherical sugar granules (NP series) were used, rapidly disintegrating tablets could be prepared by the conventional direct compression method. According to the results of moment analysis, the mean residence time (MRT) obtained between both rapidly disintegrating and conventional tablets indicates that the mean absorption time (MAT) from these tablets is approximately 60 and 90 min, respectively. This difference in MAT between the two tablets may be caused by the difference in the sum of the mean dissolution time (MDT) and the mean disintegration time (MDIT) of these tablets. Rapidly disintegrating tablets allow rapid absorption of the drug compared with conventional tablets.

Acetaminophen↗
PubMed2001

Water-soluble constituents of Glehnia littoralis fruit.

From the water-soluble portion of the methanol extract of the fruit of Glehnia littoralis Fr. SCHMIDT ex MIQ. (Umbelliferae; "hamabofu" in Japanese), thirty compounds, including three new monoterpenoids and a new monoterpenoid glucoside, a new benzofuran glucoside, a new alkyl glucoside, and a new glucide, were obtained. Their structures were clarified by spectral investigation.

Fruit↗
PubMed2001

Water-soluble constituents of ajowan.

From the water-soluble portion of the methanol extract of the fruit of Carum ajowan (ajowan), which has been used as a spice and medicine, 25 compounds, including five new monoterpenoid glucosides, a new monoterpenoid, two new aromatic compound glucosides, and two new glucides, were obtained. Their structures were clarified by spectral investigation.

Apiaceae↗
PubMed2001

Optimization of atrioventricular delay and follow-up in a patient with congestive heart failure with an implanted DDD pacemaker: case report.

It has been reported that cardiac function can be improved by implanting a DDD pacemaker (PM) and setting a short atrioventricular (AV) delay in patients with impaired cardiac function. A previous report found that the critical AV delay that induces diastolic mitral regurgitation (MR) may represent the upper limit of the optimal AV delay. The optimal AV delay can be predicted by a simple method: slightly prolonged AV delay minus the interval between the end of the atrial kick and complete closure of the mitral valve (duration of diastolic MR) at the AV delay setting. The patient was a 84-year-old man with an old myocardial infarction. He had repeated admissions to hospital for congestive heart failure. ECG showed prolongation of the PQ interval (0.28 s) and complete left bundle branch block. Cardiac function was improved by AV sequential pacing when the AV delay was set at 120ms. After DDD-PM implantation, the cardiothoracic ratio decreased from 57 to 45% and cardiac function was improved from New York Heart Association class III to I. The AV delay was optimized during follow-up. Four years after PM implantation, the patient was in good condition without further hospital admission.

Aged↗
PubMed2001

Relationship between myocardial damage and C-reactive protein levels immediately after onset of acute myocardial infarction.

The present study investigated the relationship between myocardial damage and C-reactive protein (CRP) levels, with no increase in creatine kinase (CK) activity, immediately after the onset of acute myocardial infarction (AMI) in 85 patients with their first reperfused anterior AMI without CK elevation on admission and no ischemic events during hospitalization. Patients were classified into those with low levels (<0.3 mg/dl) of CRP (Group L; n=67) and those with high levels (> or =0.3 mg/dl) of CRP (Group H; n=18). Group H had a higher proportion of patients with a history of preinfarction angina (89 vs 55%, p<0.01), especially unstable angina. SigmaST in leads V1-6 on admission ECG was lower in Group H than in Group L (14+/-7 vs 21+/-13 mm, p<0.05). Predischarge left ventriculography showed that the left ventricular global ejection fraction (55+/-11 vs 48+/-10%, p<0.01) and SD/chord at the left anterior descending artery lesion (-1.7+/-0.9 vs -2.3+/-0.9, p<0.01) were better in Group H. Multivariate analysis demonstrated that both CRP on admission (p=0.011) and preinfarction angina (p=0.002) were independently associated with better regional wall motion (SD/chord >-2.0) before discharge. These results suggest that the clinical situation of elevated CRP immediately after onset is associated with less myocardial damage and better left ventricular function in reperfused anterior AMI.

Aged↗
PubMed2001

Differences in inflammatory activity at the onset of acute myocardial infarction according to the clinical presentation of preinfarction angina.

It is unknown whether the pathogenetic mechanisms underlying acute myocardial infarction (AMI) differ according to the clinical presentation of preinfarction angina, so the present study measured plasma levels of C-reactive protein (CRP) in 280 patients with AMI in whom serum creatine kinase levels were normal on admission and increased subsequently. Patients were classified into 3 groups according to the type of preinfarction angina: no angina (n=95), stable angina (n=48), and unstable angina (n= 137). Patients with unstable angina were subdivided according to the Braunwald classification: class IB (n=39), class IIB (n=22), and class RIB (n=76). There were no differences among the 5 groups in baseline characteristics. CRP on admission was significantly higher and the level of physical activity at symptom onset was significantly lower in the Braunwald class RIB group than in the other groups, but no differences were observed among the other groups. Patients with preinfarction Braunwald class IIB unstable angina had higher CRP levels on admission and symptom onset at a lower level of physical activity. In such patients, the pathogenetic mechanisms may differ from those in other subsets of patients with AMI and active inflammation may play a more important role in AMI onset.

Acute-Phase Reaction↗
PubMed2001

Microvascular angina in a patient with aortic stenosis.

A 39-year-old woman had exercise-induced ST segment depression associated with chest pain. Cardiac evaluation revealed moderate aortic stenosis (AS), related to the bicuspid valves, with an aortic mean pressure gradient of 22 mmHg, a calculated aortic valve area of 1.3 cm2 and normal left ventricular (LV) peak systolic and end-diastolic pressures, but no LV hypertrophy, resulting in normal LV wall stress. Although the coronary arteries were angiographically normal, rapid atrial pacing and an intracoronary papaverine injection revealed a significantly decreased coronary flow reserve (CFR), which may have played an important role in the pathogenesis of angina pectoris in this patient. Though the CFR is usually decreased in patients with AS, as well as in microvascular angina, in this particular case, it appeared to have decreased as a consequence of microvascular dysfunction rather than of AS-related mechanisms.

Adult↗
PubMed2001

The transposition pattern of the Ac element in tobacco cultured cells.

We investigated physical distances and directions of transposition of the maize transposable element Ac in tobacco cultured cells. We introduced a T-DNA construct that carried a non-autonomous derivative of Ac (designated dAc-I-RS) that included sites for cleavage by restriction endonuclease MluI. Another cleavage site was also introduced into the T-DNA region outside of the dAc-I-RS transposable element. The tobacco cultured cell line BY-2 was transformed with the T-DNA and several transformed lines that had a single copy of the T-DNA at a different chromosomal location were isolated. These lines were co-cultured with Agrobacterium tumefaciens cells that carried a cDNA for the Ac transposase gene under the control of various promoters. Sublines of cultured cells in which dAc-I-RS had been transposed, were isolated. The genomic DNAs of these sublines were isolated and digested with MluI. Sizes of DNA segments generated by digestion were determined by pulse-field gel electrophoresis. Our results showed that 20 to 70% of transposition events had occurred within several hundreds kilo-base pairs (kb) on the same chromosome. These results demonstrate that the Ac-Ds element preferentially transposed to regions near the original site in a tobacco chromosome. In addition, the present results are an example of asymmetric transposition as demonstrated by the distance of transposition on the chromosome.

Agrobacterium tumefaciens↗
PubMed2001

The relationship between a leaf-rolling moth (Dactylioglypha tonica) and fungi covering the cocoon.

To discover the relationship between a leaf-rolling moth and the fungi densely covering its cocoons, the rolled nest leaves were collected in two districts in Japan and antibacterial properties of the fungi were examined. Cocoons and fungi isolated from the nest were classified into 5 categories by the growth stages of the insects, and 7 categories based on taxonomic properties and pigment productivity, respectively. The dominant genus was Penicillium in each location. However, the composition of the fungal categories was different and seemed to depend on their circumstances. From all cocoons with larvae, the strains that belonged to the same fungal category and produced the same antibiotic (deoxyherqueinone) were isolated. From these results, the species-specific relationship between the insect and fungi or fungal products was considered to be not extremely tight, and it was suggested the period of the larval spinning of the cocoon is a key stage of this unique relationship.

Animals↗
PubMed2001

Optimization of atrioventricular delay and follow-up in a patient with congestive heart failure and with bi-ventricular pacing.

Cardiac function is improved by bi-ventricular pacing in patients with severe reduced cardiac function. Atrioventricular (AV) delay optimization is also important in this therapy. However, the AV delay required to achieve the optimal AV synchrony varied from time to time. We have reported that the critical AV delay that induces diastolic mitral regurgitation (MR) may represent the upper limit of the optimal AV delay. The optimal AV delay can be predicted by a simple method; slightly prolonged AV delay-interval between the end of atrial kick and complete closure of the mitral valve (duration of diastolic MR) at the AV delay setting. [Case] 60 year old Japanese male with dilated cardiomyopathy. He was repeatedly admitted to our hospital due to congestive heart failure. Ejection fraction was 14%. ECG showed complete left bundle branch block and his PQ interval was 0.22 sec. He was dependent on intravenous injections of catecolamine and could not be discharged from the hospital for over one year. Optimal AV delay was predicted as 80 msec during bi-ventricular pacing by our formula. Cardiac output was 4.9, 6.0, 5.1 l/min when the AV delay was set at 50, 80, 110 msec. Cardiac function was improved from NYHA class III to II and he has been relieved from the dependency on intravenous catecholamine injections. AV delay was optimized (70-100 msec) by our method during follow-up for one year. This case indicates that AV delay optimization is important in bi-ventricular pacing.

Atrioventricular Node↗
PubMed2001

Human identification from forensic materials by amplification of a human-specific sequence in the myoglobin gene.

We developed a method for human identification of forensic biological materials by PCR-based detection of a human-specific sequence in exon 3 of the myoglobin gene. This human-specific DNA sequence was deduced from differences in the amino acid sequences of myoglobins between humans and other animal species. The new method enabled amplification of the target DNA fragment from 30 samples of human DNA, and the amplified sequences were identical with that already reported. Using this method, we were able to distinguish human samples from those of 21 kinds of animals: the crab-eating monkey, horse, cow, sheep, goat, pig, wild boar, dog, raccoon dog, cat, rabbit, guinea pig, hamster, rat, mouse, whale, chicken, pigeon, turtle, frog, and tuna. However, we were unable to distinguish between human and gorilla samples. This method enabled us to detect the target sequence from 25 pg of human DNA, and the target DNA fragment from blood stored at 37 degrees C for 6 months, and from bloodstains heated at 150 degrees C for 4 h or stored at room temperature for 26 years. Herein we also report a practical application of the method for human identification of a bone fragment.

Amino Acid Sequence↗
PubMed2001

Acquired hemophilia A in a patient with systemic lupus erythematosus.

A patient with systemic lupus erythematosus (SLE) developed acquired hemophilia A. The patient, a 24-year-old Japanese woman, was referred to our hospital because of uncontrollable bleeding following a tooth extraction. Laboratory examination revealed prolonged APTT (116 seconds), reduced factor VIII activity (2.8 %) and the presence of factor VIII inhibitor at a titer of 46.5 Bethesda units/ml. Transfusion of prothrombin complex concentrate and activated prothrombin complex concentrate followed by administration of prednisolone and cyclophosphamide successfully arrested bleeding and reduced the factor VIII inhibitor level. Acquired hemophilia A is a rare but lethal condition. Rapid diagnosis and introduction of adequate therapies are critical.

Adult↗
PubMed2001

Cross-bridge and calcium behavior in ferret papillary muscle in different thyroid states.

X-ray diffraction studies were made using synchrotron radiation on ferret right ventricular papillary muscle under three different thyroid states: euthyroidism, hyperthyroidism, and hypothyroidism. The latter two states were induced by treatment with L-thyroxine and methimazole, respectively. The X-ray equatorial reflections were recorded at a time resolution of 10 ms to study the mass movement of myosin cross-bridges from thick to thin filaments. The myosin isomer content was measured by gel electrophoresis which showed that V3 isomer was predominant in euthyroid muscle and 27% of myosin was V1 isomer in hyperthyroid muscle. The intracellular free Ca concentration was measured by using the aequorin method. The peak Ca concentration was similar in all three states, but in the hypothyroid state the time-to-peak was longer and the decay was slower. The time-to-peak of twitch tension was shorter in hyperthyroidism and longer in hypothyroidism than in euthyroidism. The different time courses of twitch tension in different thyroid states accompanied a cross-bridge movement which closely followed the tension development. In hyperthyroidism, the cross-bridge movement significantly preceded tension development, suggesting that hyperthyroid myosin (V1) has a longer latency period between the shift to the vicinity of the thin filament and force development.

Animals↗