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Biomedical subjects

A Kurihara

Publications and source records attributed to A Kurihara.

At least 19 recordsLinked to original sources
PubMed1995

Nucleosides and nucleotides. 141. Chemical stability of a new antitumor nucleoside, 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine in alkaline medium: formation of 2'-C-cyano-2'-deoxy-1-beta-D-ribo-pentofuranosylcytosine and its antitumor activity.

We have designed 2'-C-cyano-2'-deoxy-1-beta-D-arabino- pentofuranosylcytosine (CNDAC) as a potential mechanism-based DNA-strand-breaking nucleoside, which showed potent tumor cell growth inhibitory activity against various human tumor cell lines in vitro and in vivo. When measuring the pKa of the 2' alpha-proton of CNDAC, we found that CNDAC epimerized to 2'-C-cyano-2'-deoxy-1-beta-D-ribo-pentofuranosylcytosine (CNDC) with concomitant degradation of both CNDAC and CNDC to cytosine and 1,4-anhydro-2-C-cyano-2-deoxy-D-erythro-pent-1- enitol. Kinetic analysis of these reactions showed that abstraction of the acidic 2'-proton of CNDAC and CNDC initiated the reactions, which quickly reached an equilibrium. In the equilibrium, a concentration ratio of CNDAC and CNDC was about 3:5. Concomitant degradation of these nucleosides was found to be rather slow. Deuterium incorporation experiments with CNDAC in a D2O buffer suggested the mechanism of the beta-elimination reactions is an E1cB type. These epimerization and degradation reactions were found even in neutral conditions (pH 7.5) and also occurred in RPMI 1640 cell culture medium. The discovery of which nucleoside possesses the predominate tumor cell growth inhibitory activity was important. While both nucleosides showed potent tumor cell growth inhibitory activity against three human tumor cell lines (colon carcinoma WiDr, small cell lung carcinoma SBC-5, and stomach carcinoma MKN-74 cells) in 48 h of incubation, in 20 min of incubation, CNDAC was 11-50 times more effective than CNDC. In vivo antileukemic activity of these nucleosides against a mouse P388 model, CNDAC was obviously superior to CNDC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

Effects of sematilide, a novel class III antiarrhythmic agent, on action potential in guinea pig atrium.

Electrophysiological effects of sematilide, a novel class III antiarrhythmic agent, were examined and compared with those of (+/-)sotalol in guinea pig left atrium by a conventional microelectrode technique. Application of 0.1-1000 microM sematilide or 1-1000 microM (+/-)sotalol concentration-dependently prolonged the duration of action potentials (APD) that were elicited by electrical stimulation at 1 Hz. Other parameters of action potentials such as the maximum upstroke velocity of phase 0 depolarization, action potential amplitude and resting membrane potential were not affected significantly by these drugs in the concentration ranges employed. The prolongation of APD by sematilide or (+/-)sotalol was accompanied by a corresponding increase in the effective refractory period (ERP). Approximately a 30% increase in ERP was obtained by the treatment with 5 microM sematilide or 100 microM (+/-)sotalol, suggesting that sematilide as a class III antiarrhythmic agent is approximately 20 times more potent than (+/-)sotalol on a molecular basis. When the stimulation rate was increased stepwise from 0.2 to 2 Hz, the relative increase in APD at 90% repolarization by the treatment with sematilide and (+/-)sotalol was slightly larger at 2 Hz than at 0.2 Hz, indicating that "reverse rate-dependence" was not observed under these conditions. These results may suggest a possibility that sematilide effectively blocks atrial arrhythmia.

Action Potentials↗
PubMed1994

The effects of goshajinkigan, a herbal medicine, on subjective symptoms and vibratory threshold in patients with diabetic neuropathy.

Goshajinkigan, a herbal medicine, has long been used in Japan to alleviate the subjective symptoms of diabetic neuropathy; however, its effects have not been confirmed objectively. We evaluated its effects on subjective symptoms and on vibration sensation in patients with diabetic neuropathy. The oral administration of 7.5 g/day of Goshajinkigan for 3 months (treatment period) relieved subjective symptoms of numbness in 9 of 13 patients. When the drug was discontinued for 2 months as a washout period, the subjective symptom worsened in 7 of 13 patients. Chi-square analysis revealed significant effects of Goshajiniagan on subjective symptoms (P < 0.001 for numbness and P < 0.05 for cold sensation). Vibration sensation was evaluated by measuring vibratory threshold using an SMV-5 vibrometer. There were significant changes in vibratory thresholds by paired t-test (P < 0.05) both in the upper and the lower extremities during the treatment and washout periods. Chi-square analysis also revealed a significant effect of Goshajinkigan on vibratory threshold (P < 0.01). There was no significant change in glycosylated hemoglobin as a whole during the study. These observations confirm that Goshajinkigan relieves subjective symptoms and demonstrate that it improves vibration sensation in patients with diabetic neuropathy.

Administration, Oral↗
PubMed1993

Application of the bromophenol blue (BPB) staining method to rat fetal cartilage previously stained with alizarin red S.

The application of a convenient bromophenol blue (BPB) cartilage staining method on rat fetal skeleton, previously stained with alizarin red S, was investigated. This staining method made it possible to observe uncertain cartilage anomalies and unossified caudal vertebrae, which were poorly detected by single staining with alizarin red S. Namely, the anomaly of chondral rib bifurcation was detected and the number of unossified caudal vertebrae in rat fetuses was demonstrated as being identical with adult rat caudal vertebrae. The BPB staining has the notice to make the pH 4 adjusted specimens and has the advantage of fading with water or ethanol at pH 8 without discoloration of alizarin red S on the bones.

Animals↗
PubMed1992

Prediction of human pharmacokinetics of panipenem-betamipron, a new carbapenem, from animal data.

The pharmacokinetic behavior of panipenem (PAPM)-betamipron (BP), a new carbapenem, in humans was successfully predicted from data collected from six animal species. PAPM and BP were biphasically eliminated from plasma after intravenous (i.v.) administration of PAPM-BP to mice, guinea pigs, rats, rabbits, monkeys, and dogs. Elimination rates of PAPM and BP were correlated with animal size: the larger the animal was, the slower the elimination was. As for PAPM and BP, log-log plots of total plasma clearance (CLtot) versus body weight and log-log plots of distribution volume at steady state (VSS) versus body weight for six animal species were linear, with high correlation coefficients. These allometric equations were extrapolated to predict CLtot and VSS for PAPM and BP in humans. In addition, concentration in plasma-time profiles for humans were predicted by using two-exponent equations fitted to the complex Dedrick plot of animal data. Predicted values for CLtot and VSS for PAPM and BP in humans agreed well with observed values in humans given 750/750 mg of PAPM-BP as an i.v. drip infusion for 30 min. Predicted concentration in plasma-time profiles for humans approximated observed profiles. Thus, the pharmacokinetics of PAPM-BP extrapolated well from animal species to humans when allometric equations and the complex Dedrick plot were used.

Animals↗
PubMed1992

The regulation of two distinct glucose transporter (GLUT1 and GLUT4) gene expressions in cultured rat thyroid cells by thyrotropin.

We investigated the glucose transporter mRNAs expressed in FRTL5, a rat thyroid cell line, and their regulation by TSH by means of the polymerase chain reaction. FRTL5 cells as well as rat thyroid tissue expressed three types of glucose transporter mRNAs: GLUT1 or erythrocyte/HepG2/brain isoform, GLUT2 or pancreatic beta-cell/liver isoform, and GLUT4 or muscle/fat isoform. GLUT1 mRNA predominated, GLUT4 mRNA was minor, and GLUT2 mRNA expression was faint. Incubation of FRTL5 cells with TSH induced a time- and concentration-dependent increase in GLUT1 mRNA levels, while GLUT4 mRNA levels were decreased. The response of GLUT1 mRNA to TSH was evident at 3 h, and the maximal response was achieved at 12 h. TSH at a dose of 1 mU/ml elicited an approximately 3-fold increase in GLUT1 mRNA levels. (Bu)2cAMP (1 mM), 8-bromo-cAMP (1 mM), and forskolin (50 microM) mimicked the effect of TSH on GLUT1 and GLUT4 mRNA levels. The increase in GLUT1 mRNA by TSH was correlated with the increase in GLUT1 protein and the increase in 2-deoxyglucose transport activity. These observations suggest that in thyroid cells, TSH stimulates glucose transport at least in part by enhancing GLUT1 gene expression, and that the effect of TSH on GLUT1 and GLUT4 mRNA levels is mediated by a cAMP-dependent pathway.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Neurotoxicity of panipenem/betamipron, a new carbapenem, in rabbits: correlation to concentration in central nervous system.

The neurotoxic potential of panipenem/betamipron (PAPM/BP), a new carbapenem antibiotic, was compared with that of imipenem/cilastatin (IPM/CS). The drug concentration in cerebrospinal fluid (CSF) at the onset of epileptogenic electroencephalographic (EEG)-activity and the drug distribution into the central nervous system (CNS) were evaluated. Epileptogenic reactions correlated well with drug levels in CSF, but not with drug levels in circulating plasma. The concentration of PAPM in CSF at the onset of epileptogenic EEG-activity was almost twice that of IPM, suggesting that neurotoxic activity of PAPM is about half that of IPM. In addition, in terms of incidence percent for the epileptogenic EEG-activity, PAPM/BP was found to be less toxic than IPM/CS within the dose of 1.0-1.2 g/kg. Concentrations of PAPM in CSF and brain extracellular fluid after PAPM/BP i.v. infusion were comparable with those of IPM after IPM/CS infusion, indicating the similar characteristics of distribution into the CNS for the two antibiotics. From these results of pharmacologic effects and drug distributions, it is suggested that the neurotoxicity of PAPM/BP is less than half that of IPM/CS.

Alanine↗
PubMed1992

Prediction of human pharmacokinetics of panipenem, a new carbapenem antibiotic, from animal data.

The prediction of human pharmacokinetics of Panipenem (PAPM), which is a new carbapenem antibiotic, was investigated using animal data. The plasma concentration-time curve after intravenous administration of PAPM in each animal showed biexponential elimination. There were good allometric correlations between pharmacokinetic parameters (CLtotal and Vd,ss) calculated from the plasma concentration in animal species and body weight of experimental animals. Predicted human pharmacokinetic parameters calculated by these allometric equations agreed with the values observed in humans.

Adult↗
PubMed1991

Bone destruction mechanisms in chronic otitis media with cholesteatoma: specific production by cholesteatoma tissue in culture of bone-resorbing activity attributable to interleukin-1 alpha.

To clarify specific mechanisms underlying cholesteatoma-induced bone destruction, surgical specimens of middle ear inflammatory granulation tissue with or without cholesteatoma were maintained in vitro and the bone-resorbing activity in their culture supernatants was analyzed by means of calcium release from mouse calvaria. Almost the same levels of bone-resorbing activity and prostaglandin (PG) E2 were found in the supernatants of both types of tissue. By contrast, aural polyp tissue yielded hardly any such activity or PGE2. Under the influence of indomethacin, however, only tissue with cholesteatoma produced considerable bone resorption activity, whereas PGE2 production was suppressed completely. Such activity in the cholesteatoma culture supernatant was not due to contamination of endotoxin and proved to be blocked by the introduction of anti-interleukin (IL)-1 alpha antibody into the calvarial assay system. Anti-IL-1 beta antibody had no effect on such activity. Interleukin-1 alpha was detected only in cholesteatoma tissue culture supernatants by means of enzyme-linked immunosorbent assay and by bioassay. These data suggest that the bone destruction in otitis media with cholesteatoma may be attributed to IL-1 alpha in addition to PGE2.

Animals↗
PubMed1989

[Clinical evaluation of the control of antiplatelet therapy through platelet aggregation rate on polycythemia vera associated with thrombocytosis and erythromelalgia].

A 60-years-old woman with polycythemia vera with marked thrombocytosis and intolerable erythromelalgia was presented. A single dose of 400 mg aspirin was effective to improve the pain and cyanosis. And we studied the relationship between platelet aggregation rate and symptoms after administration of several antiplatelet drugs. A single dose of 100, 200, 400 and 800 mg aspirin, 25 mg indomethacin (Id), 200 mg OKY-046, and daily dose of 300 and 600 mg dipyridamole (Dp) and 300 mg ticlopidine (Tc) were given. Aspirin, Id and OKY-046 were effective for the improvement of finger pain. The complete inhibition of spontaneous aggregation (SPA) and aggregation by 2.0 micrograms/ml of collagen were well parallel with the improvement of symptoms. But duration of effect of LKY-046 were only 6 hours. Dp and Tc were not effective for the improvement of pain, had no relation with platelet aggregation rate. The concentration level of aspirin in vivo which suppresses the platelet aggregation induced by SPA and 2.0 micrograms/ml of collagen coincided well with the concentration level of this drug which suppresses the same platelet aggregation in vitro. It seems to be useful to suppress the platelet aggregation induced by SPA and 2.0 micrograms/ml of collagen with aspirin and Id for controlling the platelet aggregation induced circulatory disturbance in patient with thrombocytosis.

Aspirin↗
PubMed1988

Transport of digoxin into brain microvessels and choroid plexuses isolated from guinea pig.

To characterize the efflux system of digoxin, a cardiac glycoside, from the brain to the blood through the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier, the accumulation of digoxin by the brain microvessel or the choroid plexus isolated from guinea pig brain was investigated. The accumulation of digoxin by the brain microvessel has a saturable component (Km = 0.163 microM, Vmax = 0.142 nmol/mL of tissue/min), with a nonsaturable component [Kd = 0.203 cell-to-medium (C:M) ratio/min] that was decreased by hypothermia (Q10 = 2.9), sulfhydryl reagent, and quinidine, but not by a metabolic inhibitor [2,4-dinitrophenol (DNP)]. It was concentration- and Na+-dependent. The accumulation of digoxin by the choroid plexus was also saturable (Km = 1.9 microM, Vmax = 3.8 nmol/mL of tissue/min), and was decreased by hypothermia (Q10 = 4.4), sulfhydryl reagents, ouabain, and quinidine, but not by metabolic inhibitors (DNP, KCN); it was also concentration- and Na+-dependent. The binding of digoxin to the homogenate of choroid plexus was one-tenth of digoxin accumulation by the intact choroid plexus, suggesting that digoxin is transported into the cells and bound to the cytosol fraction. The value of (Vmax/Km + Kd) multiplied by the total tissue weight of the microvessel per guinea pig is approximately 10-fold that of Vmax/Km multiplied by the tissue weight of the choroid plexus, although (Vmax/Km + Kd) per milliliter of the microvessel is half the Vmax/Km value of the choroid plexus. These findings suggest that digoxin can be excreted from both the brain and the cerebrospinal fluid to blood by a carrier-mediated diffusion system which is inhibited by quinidine, and that a main route of digoxin efflux from the brain to the blood is not through the blood-CSF barrier, but through the blood-brain barrier.

Animals↗
PubMed1988

Hyperostotic lumbar spinal stenosis. A review of 12 surgically treated cases with roentgenographic survey of ossification of the yellow ligament at the lumbar spine.

Although there is considerable literature concerning ossification of the posterior longitudinal ligament or the ligamentous flava (OPLL or OYL) in the cervical and thoracic spine, there are only a few references about OPLL or OYL in the lumbar spine. The authors have described lumbar spinal stenosis due to OPLL or OYL as hyperostotic lumbar spinal stenosis, and analyzed 12 surgically documented cases with this condition. The symptoms and signs of hyperostotic lumbar spinal stenosis are the same as those seen in degenerative lumbar spinal stenosis, but the degree of paraparesis is much more severe in hyperostotic lumbar spinal stenosis. Computed tomography scan imaging clearly demonstrates OPLL or OYL in the lumbar spine, although some lesions can be seen on the lateral view of a plain roentgenogram. The results of 12 surgical cases suggest that decompression laminectomy produces relief of symptoms. An analysis of 2,403 plain lumbar roentgenograms showed an incidence of 8.4% OYL in the lumbar spine, with frequent involvement of the upper and middle lumbar spine. A classification system of OYL in the lumbar spine has been developed. The entire spine should be examined before surgery on a patient with hyperostotic lumbar spinal stenosis because of a tendency to ossify spinal ligaments at other levels.

Adult↗
PubMed1988

Amidolytic kinetic assay of protein C by selective spectrophotometry in a centrifugal analyzer.

This rapid, simple amidolytic assay of protein C activity in whole plasma involves activation by protein C activator from the venom of Agkistrodon contortrix contortrix (Protac) and use of a Cobas Fara spectrophotometer programmed for kinetic assay. Plasma is incubated with activator venom in the presence or absence of antibody to human protein C in the instrument, chromogenic substrate (S-2366) is added, and the absorbance is measured at 405 nm. The difference between the absorbance of the sample plasma with and without antibody to human protein C correlated well with protein C antigen as assayed by enzyme-linked immunosorbent assay (ELISA) and the Laurell rocket technique in normal subjects, patients being treated with warfarin, and patients with liver cirrhosis or disseminated intravascular coagulation. Our mean value for protein C in normal subjects is 115.9 (SD 16.7)% for amidolytic activity, 103.0 (SD 17.4)% for ELISA, and 97.2 (SD 18.1)% for the rocket technique. The high value for normal subjects presumably includes some nonspecific amidolytic activity activated by the activator venom, as indicated by measurable activity in immuno-depleted protein C-deficient plasma. Within-run and between-run CVs were less than 5% at low, normal, and high concentrations of protein C amidolytic activity.

Centrifugation↗
PubMed1987

Uptake of propranolol by microvessels isolated from bovine brain.

To study the transport system of propranolol (PL), a basic drug, in the blood-brain barrier, the uptake of PL into isolated bovine brain microvessels was investigated. The uptake of PL was a concentrative one via saturable process (Km = 42.5 microM) that was decreased by hypothermia (Q10 = 2.2), but not by metabolic inhibitors (2,4-dinitrophenol, KCN, ouabain). Although basic drugs such as quinidine and imipramine decreased both the initial rate of uptake and the steady-state cell-to-medium concentration ratio (C/M) of PL, acidic drugs (phenobarbital, salicylic acid) did not affect them. These results suggest that PL is taken up by the endothelial cells of the isolated brain microvessels by facilitated diffusion which is specific for basic drugs and then binds to certain binding sites in the cells.

2,4-Dinitrophenol↗