Biomedical subjects

Y Katagiri

Publications and source records attributed to Y Katagiri.

At least 73 records · Page 4Linked to original sources

PubMed1995

Effects of selective phosphodiesterase type IV inhibitor, rolipram, on signal transducing phospholipases in neutrophil: inhibition of phospholipases A2, D but not C.

The effects of a selective phosphodiesterase (PDE) type IV inhibitor, rolipram, on activation of neutrophil phospholipases in response to the chemotactic peptide formyl-methiony-leucyl-phenylalanine (fMLP) were investigated. fMLP caused liberation of arachidonic acid, a precursor of eicosanoids and in the presence of 0.3% butanol, production of phosphatidylbutanol, an indicator of phospholipase D activation. Rolipram inhibited arachidonic acid release and phosphatidylbutanol formation. The inhibition was considered to be mediated through a cAMP-dependent mechanism, probably protein kinase A, because selective inhibitors for protein kinase A, H-8 or H-89 overcame the action of rolipram. The concentration-dependent inhibitory profile for phospholipase D activation was similar to that for lysosomal enzyme release, providing additional evidence for the functional link of these two events. In contrast, rolipram was without effect on fMLP-induced inositol trisphosphate production. These results indicate that this selective PDE IV inhibitor had no effect on phosphatidylinositol-specific phospholipase C activation but effectively prevented activation of phospholipases A2 and D coupled to arachidonic acid liberation and lysosomal enzyme release, respectively.

Animals↗

PubMed1995

Light removes inactivation of the A-type potassium channels in scallop hyperpolarizing photoreceptors.

The properties of light-activated and voltage dependent conductances in the hyperpolarizing photoreceptors of the isolated retina of the giant scallop (Patinopecten yessoensis) have been studied in whole-cell voltage-clamp recordings. Resting membrane potential of the cells was -35 to -60 mV in the dark. Large outward current was maintained during illumination when the cell was voltage clamped at the resting potential. Previous reports have shown that the hyperpolarizing response to light and the light-activated outward current are mediated by an increase of a conductance of K+ channels in the plasma membrane (Gorman and McReynolds, 1974; Gomez and Nasi, 1994a). This report shows that the light-activated K+ channels of this photoreceptor cell generate the voltage-dependent transient outward current in response to depolarizing voltage steps in the dark. The characteristic of this current resembles the typical voltage-dependent transient current (A-current) of molluscan neurons in the kinetics of activation and inactivation, and in the blockage by 4-aminopyridine (4-AP). However, the voltage-dependent transient current during illumination becomes a flat stable form which inactivation process disappeared. We report here that light removes inactivation of the K+ channels which generate the voltage-dependent transient outward currents in the dark.

Animals↗

PubMed1995

[Shear-induced platelet aggregation (SIPA) monitoring of hemostatic effect during platelet transfusion in a patient with Glanzmann's thrombasthenia: a comparison between SIPA and conventional platelet aggregation].

Shear-induced platelet aggregation (SIPA) in a patient with Glanzmann's thrombasthenia was examined during platelet infusion therapy. Prior to platelet infusion, SIPA measured with the modified cone-and-plate type viscometer, as well as ADP-and collagen-induced platelet aggregation measured with the conventional platelet aggregometer, were absent. The patient's SIPA after multiple infusions of platelet, in parallel with the bleeding time and the clinical hemostatic effect, improved to the normal level, while ADP-and collagen-induced platelet aggregation remained abnormal. These observations imply that SIPA is physiologically more relevant than the conventional agonist-induced platelet aggregometry in this type of the disease.

Adenosine Diphosphate↗

PubMed1994

Purification and characterization of S-adenosyl-L-methionine: norcoclaurine 6-O-methyltransferase from cultured Coptis japonica cells.

S-adenosyl-L-methionine:norcoclaurine 6-O-methyltransferase (norcoclaurine 6-O-methyltransferase), which catalyzes the transfer of the S-methyl group of S-adenosyl-L-methionine to the 6-hydroxyl group of 1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl)methyl]-6,7- isoquinolinediol (norcoclaurine), was purified from cultured Coptis japonica cells and its enzymic properties were characterized. Purified norcoclaurine 6-O-methyltransferase had apparent pI 4.7, a native molecular mass of 95 kDa (determined by gel filtration) and subunit molecular mass of 40 kDa (SDS/PAGE). The enzyme did not require a divalent cation for activity, and the addition of Fe2+, Cu2+, Co2+, Zn2+, Mn2+, or Ni2+ at 5 mM severely inhibited enzyme activity. Neither p-chloromercuribenzoate, N-methylmaleimide nor iodoacetamide inhibited enzyme activity at 1 mM. 5,6-Dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]qu inolizinium (berberine, the end-product of the biosynthetic pathway in which norcoclurine 6-O-methyltransferase catalyzes an intermediate step) also inhibited the activity by 50% at 10 mM. Norcoclaurine 6-O-methyltransferase methylated both (S)-norcoclaurine and (R)-norcoclaurine and (R,S)-norlaudanosoline. Further characterization of substrate-saturation kinetics and product inhibition of the purified enzyme indicated that norcoclaurine 6-O-methyltransferase follows a bi-bi ping-pong mechanism with Km values of 2.23 mM and 3.95 mM for (R,S)-norlaudanosoline and S-adenosyl-L-methionine, respectively, while Ki values for S-adenosylhomocysteine versus S-adenosyl-L-methionine and (R,S)-norlaudanosoline were 2.1 mM and 0.18 mM, respectively.

Amino Acid Sequence↗

PubMed1994

Prenylated flavonoids in the roots of yellow lupin.

A further investigation of the methanol-soluble compounds in yellow lupin roots has revealed a new diprenylchromone, a new coumaronochromone (lupinalbin H), a new isoflavone 5,7,4'-trihydroxy-8,3'-di-(3,3-dimethylally)isoflavone (isolupalbigenin), and some complex flavanones. The latter compounds have been identified as two known diprenylated flavanones (lonchocarpol A and euchrestaflavanone A), two diasteroisomeric pairs of dihydrofuranoflavanones (lonchocarpols C1 and C2, and lonchocarpols D1 and D2, the structures formerly proposed for lonchocarpols C and D were also reinvestigated), a new furanoflavanone (lupinenol), and three 8-prenylflavanones with an additional (2RS)-hydroxy-3-methyl-3-butenyl side chain. The structures of the latter flavanones were unambiguously identified by spectroscopic (1H NMR) comparison with 6-, 8- and 3'-prenylnaringenins chemically prepared from (2S)-naringenin. The antifungal activity of the prenylated naringenins, and of the various yellow lupin flavanones, was determined by TLC place bioassays using Cladosporium herbarum as the test fungus.

Chromatography, Thin Layer↗

PubMed1994

Integrin cytoplasmic domains mediate inside-out signal transduction.

We analyzed the binding of fibronectin to integrin alpha 5 beta 1 in various cells; in some cells fibronectin bound with low affinity (e.g., K562 cells) whereas in others (e.g., CHO), it bound with high affinity (Kd approximately 100 nM) in an energy-dependent manner. We constructed chimeras of the extracellular and transmembrane domains of alpha IIb beta 3 joined to the cytoplasmic domains of alpha 5 beta 1. The affinity state of these chimeras was assessed by binding of fibrinogen or the monoclonal antibody, PAC1. The cytoplasmic domains of alpha 5 beta 1 conferred an energy-dependent high affinity state on alpha IIb beta 3 in CHO but not K562 cells. Three additional alpha cytoplasmic domains (alpha 2, alpha 6A, alpha 6B) conferred PAC1 binding in CHO cells, while three others (alpha M, alpha L, alpha v) did not. In the high affinity alpha chimeras, cotransfection with a truncated (beta 3 delta 724) or mutated (beta 3(S752-->P)) beta 3 subunit abolished high affinity binding. Thus, both cytoplasmic domains are required for energy-dependent, cell type-specific affinity modulation. In addition, mutations that disrupted a highly conserved alpha subunit GFFKR motif, resulted in high affinity binding of ligands to alpha IIb beta 3. In contrast to the chimeras, the high affinity state of these mutants was independent of cellular metabolism, cell type, and the bulk of the beta subunit cytoplasmic domain. Thus, integrin cytoplasmic domains mediate inside-out signaling. Furthermore, the highly conserved GFFKR motif of the alpha subunit cytoplasmic domain maintains the default low affinity state.

Amino Acid Sequence↗

PubMed1994

Preferential uptake of lactosylceramide-bearing dipalmitoylphosphatidylcholine-liposomes into liver: role of membrane fluidity.

The effect of the membrane fluidity of lactosylceramide (LacCer)-bearing liposomes on their liver uptake was investigated in rats. Liposomes consisting of phosphatidylcholine (PC): cholesterol:dicetylphosphate:LacCer (7:2:1:1, molar ratio) were prepared with various fluidities using dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC) and egg PC. These liposomes were all equally stable in serum and were small enough to pass freely through the fenestrae and be taken up easily by liver cells. The LacCer modification of DPPC-liposomes markedly facilitated blood clearance, whereas no enhancing effect of LacCer was observed with egg PC- and DMPC-liposomes. Tissue distribution studies showed the preferential liver uptake of LacCer-bearing DPPC-liposomes, which was largely compatible with the rapid clearance induced by the LacCer modification. In addition, electron spin resonance (ESR) spectroscopic analysis revealed that the LacCer modification of DPPC-liposomes significantly enhanced the order parameter S, indicating that LacCer-bearing DPPC-liposomes were the most rigid of those used in this study. These observations suggest that the membrane fluidity of liposomes in vivo is a crucial factor for their preferential liver uptake.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1994

[Recent trend and development of new synthetic corticosteroids].

Corticosteroids have desirable antiinflammatory and immunosuppressive actions and are administered orally, parenterally and topically for the treatment of various diseases. The pharmacological spectrum of corticosteroids includes activities which may result in numerous adverse reactions. The development of more effective drugs, the development of preparations suitable for administration and the improvement of administration routes have been extensively studied with respect to a separation of therapeutic and toxic effects of corticosteroids. In the present paper, the recent trend and development of corticosteroids are reviewed.

Administration, Oral↗

PubMed1993

Activated platelets induce superoxide anion release by monocytes and neutrophils through P-selectin (CD62).

Activated platelets expressing P-selectin in their surfaces are known to adhere to monocytes and neutrophils. We examined the possibility that the leukocytes are functionally modified by their adhesion to activated platelets. We used human peripheral blood monocytes and neutrophils and measured superoxide anion generation by these cells cultured with platelets. The levels of superoxide anion production were found to be markedly elevated when thrombin-activated platelets were used. The extent of this enhancement was much smaller when leukocytes were cultured with resting platelets than activated platelets. The increase depended on incubation time and platelet concentration. The membranes prepared from activated platelets also induced superoxide anion production, but the culture supernatant of activated platelets did not. The enhanced superoxide anion production was inhibited by anti-P-selectin antibody, anti-sialyl-Lewis X antibody, or a soluble recombinant P-selectin fusion protein. These results indicate that the adhesion of activated platelets to the leukocytes through P-selectin was a crucial step for the activation of leukocyte function, and support the idea that activated platelets are actively involved in inflammation processes.

Base Sequence↗

PubMed1993

Deletion detection for diagnosis of Duchenne muscular dystrophy in the Japanese population--comparison between the polymerase chain reaction and the Southern blot analysis.

We compared the efficacy of the multiplex PCR with that of the cDNA analysis for detection of deletions of the DMD gene in the Japanese patients. Thirty males with DMD from 27 Japanese families were studied by the multiplex PCR, and 24 of them were also investigated by Southern blot analysis. We used five dystrophin cDNA probes for deletion analysis. A total of 19 regions were amplified by the PCR to detect deletions, 9 regions by the method of Chamberlain et al. and another 10 regions by the method of Beggs et al. Deletions were detected in 14 (52%) out of 27 DMD families by the PCR. Southern blot analysis detected deletions in 14 (64%) out of 22 families. Thirteen (93%) of the 14 DMD families with deletions detected by Southern blotting were also confirmed by the multiplex PCR. Provided care is taken in cases where the deletion is limited to a single exon, the multiplex PCR appears to be an efficient and useful alternative to conventional Southern blot analysis for detecting deletions during the prenatal and postnatal diagnosis of DMD.

Asian People↗

PubMed1993

Dependency of salivary excretion of mexiletine on the plasma concentration in rats.

The effect of steady-state plasma concentrations on the salivary excretion of mexiletine was investigated following simultaneous bolus intravenous injection of the loading dose (2.7 or 16.1 mg kg-1) and constant-rate intravenous infusion of the maintenance dose (15 or 102 micrograms min-1 kg-1) in male Wistar rats. Parotid and mandibular saliva was collected separately by stimulating salivation with a constant-rate infusion of pilocarpine (50 micrograms kg-1 min-1) in each rat. The low and high steady-state levels of mexiletine in blood plasma were attained at 0.259 +/- 0.123 and 1.616 +/- 0.475 micrograms mL-1, respectively, within the first 1-2 h after drug administration. Similarly, the two different steady-states in both parotid and mandibular saliva were attained. Although the mexiletine levels in both types of saliva were lower than that in plasma, the drug level in parotid saliva was always higher than that in mandibular saliva at any steady-state (P < 0.001 or 0.01). In parotid saliva, the high steady-state produced greater saliva to plasma drug concentration ratios (S/P ratio, 0.475 +/- 0.160) than that (0.386 +/- 0.131) at the low steady-state (P < 0.05). The S/P ratio for mandibular saliva at the high (0.204 +/- 0.060) steady-state was also greater than that at the low (0.158 +/- 0.050) steady-state (P < 0.01). These changes in the S/P ratio could not be explained by the pH for either parotid or mandibular saliva, but partially by the change in the unbound fraction of the drug which tended to be consistent with that in the ratio for both salivary glands. These findings suggest that the salivary excretion of mexiletine may be dependent on the plasma unbound concentration in rats.

Animals↗

PubMed1993

The dysfunction of calcium-ATPase pump in double negative T cells of autoimmune-prone mice.

Double negative (DN) T cells expanding in peripheral lymphoid tissues in mice bearing lymphoproliferation (lpr) gene are generally unresponsive to mitogens, antigens, and anti-T cell receptor (TCR) or anti-CD3 monoclonal antibodies (mAb). In response to the stimulation with 0.125-5.0 microM ionomycin, control T cells sustained an increase in intracellular free calcium ([Ca2+]i), while DN lpr T cells showed a gradual fall following initial rapid increase in [Ca2+]i. Such gradual fall in [Ca2+]i was overcome by the addition of endoplasmic and sarcoplasmic reticulum Ca(2+)-ATPase inhibitor or high dose (10 microM) of ionomycin. The requirement of high concentration of calcium ionophore for the sustained increase of [Ca2+]i in lpr DN T cells is due to dysfunction of Ca(2+)-ATPase pump.

Animals↗

PubMed1993

The induction of J11d antigen on double negative T cells of MRL/Mp-Lpr/Lpr mice by high dose calcium ionophore.

Mice homozygous for the lymphoproliferation (lpr) gene spontaneously develop autoimmune syndrome. These mice were characterized by the massive accumulation of double negative (DN) T cells. Although peripheral T cells in normal mice do not express J11d antigen, those abnormal DN T cells in autoimmune-prone mice express J11d antigen. In this study, the mechanisms that control the expression of J11d antigen are analyzed. High concentration of calcium ionophore alone induces the expression of J11d antigen, but not of CD4, CD8, and activation antigens such as interleukin 2 receptor as well as transferrin receptor by J11d- DN T cells from lpr mice. The expression of J11d antigen is primarily regulated at the transcription level rather than the post transcription level. Experiments using metabolic inhibitors reveal that the induction of J11d antigen requires the activation of not only a Ca2+/calmodulin- but also protein kinase C-dependent signaling pathway. Furthermore, J11d- DN thymocytes from control mice share the similar functional property with DN lpr T cells in J11d antigen inducibility.

Animals↗

PubMed1992

Effect of fenbufen on the pharmacokinetics of sparfloxacin in rats.

The effects of fenbufen on the serum concentrations and penetration into the brain and CSF of sparfloxacin (AT-4140), a new quinolone antibacterial agent, were investigated in rats. At designated times after a bolus iv dose of sparfloxacin 10 mg/kg with or without fenbufen 20 mg/kg, arterial blood, CSF and whole brain were simultaneously collected from each rat. Sparfloxacin concentrations were assayed by HPLC. Serum concentration of sparfloxacin declined bi-exponentially with time and was not changed by coadministered fenbufen. Binding sparfloxacin to serum protein slightly decreased after the coadministration. No elevation of sparfloxacin concentrations was observed in either brain or CSF after coadministration with fenbufen except for only a few time-points. The pharmacokinetic analysis based on the physiological model indicated that fenbufen did not affect the permeability across the blood-brain or blood-CSF barrier. These results suggest that fenbufen may be unlikely to affect the pharmacokinetics, involving the entry into the central nervous system, of sparfloxacin.

Algorithms↗

PubMed1992

Effect of fenbufen on the entry of new quinolones, norfloxacin and ofloxacin, into the central nervous system in rats.

The entry of two new quinolone antibacterial agents, norfloxacin and ofloxacin, into the central nervous system (CNS) of rats, and the effect of fenbufen on this was investigated. At various times after the administration of a bolus intravenous dose of norfloxacin or ofloxacin (10 mg kg-1) with or without fenbufen (20 mg kg-1), serum and cerebrospinal fluid (CSF) samples and whole brain were collected from the rats and the concentration of norfloxacin or ofloxacin in each sample was determined. Serum concentrations of both quinolones declined biexponentially with time and were significantly elevated by coadministration with fenbufen at the terminal phase. The fractions of these quinolones bound to serum protein were not altered by coadministration with fenbufen. Coadministered fenbufen raised the brain concentrations of both quinolones but did not affect their brain to serum unbound concentration ratios. In contrast, CSF to serum unbound concentration ratios as well as CSF concentrations of norfloxacin and ofloxacin were elevated by coadministration with fenbufen. Apparent diffusional clearances between blood and CSF of norfloxacin and ofloxacin estimated by the physiological model analysis increased by 1.9 and 2.6 times, respectively, after coadministration with fenbufen. These findings suggest that coadministered fenbufen may facilitate the entry of norfloxacin and ofloxacin into the CNS.

Animals↗

PubMed1992

Salivary excretion of mexiletine after bolus intravenous administration in rats.

Salivary excretion of mexiletine was investigated following bolus intravenous administration (10 mg kg-1) in rats. Parotid and mandibular saliva was collected separately by stimulating salivation with constant rate infusion of pilocarpine (3 mg kg-1 h-1). The mexiletine levels in blood plasma and parotid and mandibular saliva declined biexponentially with time in almost parallel fashion. Although the mexiletine levels in both types of saliva were lower than that in plasma, the drug level in parotid saliva was always higher than that in mandibular saliva. Significant correlations were observed when all data relating mexiletine concentration in plasma and saliva were included (P less than 0.001). The saliva/plasma drug concentration ratios (S/P ratios) did not vary to a large extent (0.56 +/- 0.10 for parotid saliva, 0.21 +/- 0.06 for mandibular saliva), but there was a consistent tendency for the higher plasma drug levels in the distribution phase to produce relatively high S/P ratios for both parotid and mandibular saliva. Moreover, the plasma mexiletine levels calculated by the equation of Matin et al (1974) employing the observed values for the saliva drug level, saliva pH and free fraction of mexiletine in plasma were significantly higher than the observed drug levels. Therefore, it is suggested that the salivary excretion of mexiletine could not be explained quantitatively by simple, passive secretion based on pH-partition theory.

Animals↗

PubMed1992

Pharmacokinetics of [6]-gingerol after intravenous administration in rats with acute renal or hepatic failure.

The pharmacokinetics of [6]-gingerol were investigated in rats with acute renal failure induced by bilateral nephrectomy, or those with acute hepatic failure induced by a single oral administration of carbon tetrachloride (CCl4), to clarify the contribution of the kidney and liver to the elimination process of [6]-gingerol. After bolus intravenous administration, a plasma concentration-time curve of [6]-gingerol was illustrated by a two-compartment open model. There was no significant difference in either the plasma concentration-time curve or any pharmacokinetic parameters between the control and nephrectomized rats. It is suggested, therefore, that renal excretion does not contribute at all to the disappearance of [6]-gingerol from plasma in rats. In contrast, hepatic intoxication with CCl4 elevated the plasma concentration of [6]-gingerol at the terminal phase. Its elimination half-life increased significantly, from 8.5 to 11.0 min, in CCl4-intoxicated rats. The extent of [6]-gingerol bound to serum protein was more than 90% and was affected very slightly by the CCl4-intoxication. These aspects indicate that [6]-gingerol is eliminated partly by the liver.

Acute Disease↗

PubMed1992

Interaction of platelets and blood vessels--vascular injuries induced by platelet activation in vivo.

We have found that vascular injuries are induced by intravascular aggregation of platelets activated by arachidonic acid (AA) or ADP. The characteristic findings are the appearance of vacuoles in endothelial cells and eventual deendothelialization. In deendothelialized regions, formation of platelet thrombi was observed. The platelets in the thrombi were stained with 2T60, a monoclonal antibody that recognizes activated platelets. The change was more remarkable in the AA-injected animals because AA has a stronger platelet activating effect and a detergent effect on the endothelium. The ADP-injection experiments clarified the role of platelets in vascular injury. These findings suggest that activated platelets play a role in the genesis of vascular injuries, and that their role is related to thrombus formation.

Adenosine Diphosphate↗