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1.
Rev Sci Instrum ; 93(10): 103540, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-36319310

ABSTRACT

We propose a combined use of a Pockels electro-optic sensor with a pickup loop coil (Bdot probe) for the measurement of magnetic fluctuations in plasmas. In this method, induced fluctuating voltage on the coil loop is converted into an optical signal by a compact electro-optic sensor in the vicinity of the measurement point and is transferred across optical fiber that is unaffected by electric noise or capacitive load issues. Compared with conventional Bdot probes, the electro-optic Bdot probe (1) is electrically isolated and free from noise pickup caused by the metallic transmission line and (2) can be operated at a higher-frequency range because of the smaller capacitance of the operation circuit, both of which are suitable for many plasma experiments. Conversely, the sensitivity of the current electro-optic Bdot probe arrangement is still significantly lower than that of conventional Bdot probes. A preliminary measurement result with the electro-optic Bdot probe showed the detection of a magnetic fluctuation signal around the cyclotron frequency range in the RT-1 magnetospheric plasma experiment.

2.
Phys Rev Lett ; 104(23): 235004, 2010 Jun 11.
Article in English | MEDLINE | ID: mdl-20867249

ABSTRACT

A magnetospheric configuration gives rise to various peculiar plasma phenomena that pose conundrums to astrophysical studies; at the same time, innovative technologies may draw on the rich physics of magnetospheric plasmas. We have created a "laboratory magnetosphere" with a levitating superconducting ring magnet. Here we show that charged particles (electrons) self-organize a stable vortex, in which particles diffuse inward to steepen the density gradient. The rotating electron cloud is sustained for more than 300 s. Because of its simple geometry and self-organization, this system will have wide applications in confining single- and multispecies charged particles.

3.
Clin Exp Obstet Gynecol ; 35(1): 35-40, 2008.
Article in English | MEDLINE | ID: mdl-18390078

ABSTRACT

PURPOSE: To investigate a possible association between uterine leiomyomas and catechol-O-methyltransferase (COMT) polymorphisms in a Japanese population. METHODS: We compared the allele frequencies and genotype distributions of the exon 4 NlaIII restriction site polymorphism (RSP), the P2 promoter HindIII RSP at -1217, and the exon 6 BglI RSP in the COMT gene in 250 leiomyoma cases and 182 controls using polymerase chain reaction-restriction fragment-length polymorphism analysis. RESULTS: No significant differences in allele frequencies and genotype distributions of the exon 4 NlaIII RSP, the P2 promoter HindIII RSP at -1217, and the exon 6 BglI RSP were found between uterine leiomyoma cases and controls. Moreover, no associations were noted between these three polymorphisms in COMT genes and leiomyoma size or a family history of uterine leiomyomas. CONCLUSION: COMT gene polymorphisms are unlikely to be associated with an increased risk of uterine leiomyomas in a Japanese population.


Subject(s)
Catechol O-Methyltransferase/genetics , Genetic Predisposition to Disease/genetics , Leiomyomatosis/genetics , Polymorphism, Restriction Fragment Length/genetics , Uterine Neoplasms/genetics , Adult , Alleles , Case-Control Studies , Female , Genotype , Humans , Japan , Middle Aged
4.
Cryobiology ; 50(3): 264-72, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15925578

ABSTRACT

The effect of a series of amino acids on the eutectic behavior of NaCl solutions at isotonic concentration has been studied by differential scanning calorimetry. The inclusion of different amino acids had different effects on eutectic formation. The amino acids were grouped into four categories based on their effect on eutectic formation: category C were amino acids that had no effect on eutectic formation; category D amino acids inhibited eutectic formation; category T amino acids shifted the melting of the eutectic to a lower temperature; category E amino acids caused the formation of a new eutectic with a melting temperature approximately -5 degrees C. The mechanism of these different effects on eutectic behavior is discussed, based on the chemical structure of the amino acids.


Subject(s)
Amino Acids/chemistry , Calorimetry, Differential Scanning , Crystallization , Sodium Chloride/chemistry , Cryoprotective Agents/chemistry , Freezing , Isotonic Solutions/chemistry
5.
Phys Rev Lett ; 92(25 Pt 1): 255005, 2004 Jun 25.
Article in English | MEDLINE | ID: mdl-15245020

ABSTRACT

A pure-electron plasma has been confined in a toroidal magnetic-surface configuration for as long as classical diffusion time due to neutral collisions. By controlling the potential of the internal conductor, long-term stable confinement of electrons has been achieved in a toroidal geometry.

6.
Phys Rev E Stat Nonlin Soft Matter Phys ; 65(3 Pt 2B): 036409, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11909264

ABSTRACT

Injection of charged particle beam into a toroidal magnetic trap enables a variety of interesting experiments on non-neutral plasmas. Stationary radial electric field has been produced in a toroidal geometry by injecting electrons continuously. When an electron gun is placed near an X point of magnetic separatrix, the electron beam spreads efficiently through chaotic orbits, and electrons distribute densely in the torus. The current returning back to the gun can be minimized less than 1% of the total emission.

7.
J Bone Joint Surg Am ; 83(12): 1835-9, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11741063

ABSTRACT

BACKGROUND: The clinical diagnosis of tarsal tunnel syndrome lacks objectivity and consistency. We have devised a new diagnostic physical examination test in which the tibial nerve is compressed as it runs beneath the flexor retinaculum behind the medial malleolus. In this test, the ankle is passively maximally everted and dorsiflexed while all of the metatarsophalangeal joints are maximally dorsiflexed and held in this position for five to ten seconds. METHODS: We performed this test on fifty normal volunteers (100 feet) and on thirty-seven patients (forty-four feet) treated operatively for tarsal tunnel syndrome between 1987 and 1997. We performed the maneuver both preoperatively and postoperatively and recorded any consequent changes in the signs and symptoms; during the operation we observed the altered anatomical relationships in the tarsal tunnel that were produced by the maneuver. The average duration of follow-up was three years and eleven months. RESULTS: Before the operation, the signs and symptoms of tarsal tunnel syndrome were intensified or induced by the maneuver in fifteen of the twenty feet of the patients who reported numbness, in fifteen of the seventeen feet of those who reported pain alone, and in six of the seven feet of those who had combined numbness and pain. Local tenderness was intensified in forty-two of forty-three feet, and it was induced in one foot in which it had been previously absent. A Tinel sign became more pronounced in forty-one feet, and the sign was induced in three feet in which it had been absent previously. During the operation, the tibial nerve was stretched and compressed beneath the laciniate ligament when the ankle was dorsiflexed, the heel was everted, and the toes were dorsiflexed. Preoperative signs and symptoms disappeared on an average of 2.9 months after the operation, and they could not be induced by repeating the test except in three patients, all of whom had tarsal tunnel syndrome subsequent to a fracture of the calcaneus. In the normal volunteers, no symptoms or signs could be induced by the test. CONCLUSION: This new physical examination test is effective in facilitating the diagnosis of tarsal tunnel syndrome.


Subject(s)
Physical Examination/methods , Tarsal Tunnel Syndrome/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Tarsal Tunnel Syndrome/surgery , Tibial Nerve/physiopathology
8.
Biochem Biophys Res Commun ; 289(5): 1282-6, 2001 Dec 21.
Article in English | MEDLINE | ID: mdl-11741334

ABSTRACT

Using a fluorescent differential display (FDD) technique, a novel cDNA was identified by screening for gene expressed differentially between the Dunn osteosarcoma cell line and the LM8 cell line, an isolated variant of the Dunn cell line that has high metastatic potential to the lung. Molecular cloning of the cDNA revealed the clone has similarity to a bacterial fermentation enzyme, the citrate lyase beta-subunit (CL-beta). Northern blot and competitive reverse transcription-PCR (RT-PCR) analysis revealed up-regulation of the gene in the LM8 cell line. An RNA Master blot indicated that the mRNA encoding CL-beta is expressed abundantly in murine heart, liver, and kidney. A human expressed sequence tag (EST) database search suggested that a similar cDNA is expressed in humans. A gene with identical sequence is located on chromosome 13 in the genome database (Sanger centre, UK). These data suggest that a citrate fermentation pathway may exist in eukaryotes including mammals.


Subject(s)
Multienzyme Complexes/chemistry , Multienzyme Complexes/genetics , Oxo-Acid-Lyases/chemistry , Oxo-Acid-Lyases/genetics , Animals , Base Sequence , Bone Neoplasms/enzymology , Bone Neoplasms/genetics , Chromosomes, Human, Pair 13/genetics , Cloning, Molecular , DNA, Complementary/genetics , Databases, Nucleic Acid , Expressed Sequence Tags , Female , Gene Expression Profiling , Genes, Bacterial , Humans , Klebsiella pneumoniae/enzymology , Klebsiella pneumoniae/genetics , Lung Neoplasms/enzymology , Lung Neoplasms/genetics , Lung Neoplasms/secondary , Male , Mice , Molecular Sequence Data , Osteosarcoma/enzymology , Osteosarcoma/genetics , Protein Subunits , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Nucleic Acid , Species Specificity , Tissue Distribution , Tumor Cells, Cultured , Up-Regulation
9.
Clin Exp Pharmacol Physiol ; 28(9): 743-7, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11553034

ABSTRACT

1. In the present study, we investigated the effects of hydrogen peroxide (H2O2) on the 4-aminopyridine-sensitive transient outward current (I(TO)) in rabbit atrial myocytes using the amphotericin B-perforated patch voltage-clamp method. 2. Superfusion of myocytes with H2O2 at 100 micromol/L gradually slowed the time-course of inactivation of I(TO) and increased the peak by 9% (n = 9). The H2O2-induced slowing of I(TO) inactivation was concentration dependent (over the concentration range 10 micromol/L to 1 mmol/L). These effects were hardly reversed by washout of H2O2, but were quickly abolished by dithiothreitol (2 mmol/L). 3. Bisindolylmaleimide (100 nmol/L), an inhibitor of protein kinase C, significantly attenuated the H2O2-induced effects on I(TO). 4. These results suggest that rabbit atrial I(TO) is susceptible to oxidation by H2O2 at concentrations relevant to those encountered during ischaemia/reperfusion and that protein kinase C modulates the effects of H2O2.


Subject(s)
Heart Atria/drug effects , Hydrogen Peroxide/pharmacology , Membrane Potentials/drug effects , Oxidants/pharmacology , 4-Aminopyridine/pharmacology , Animals , Atrial Function , Dithiothreitol/pharmacology , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Heart Atria/cytology , Indoles/pharmacology , Male , Maleimides/pharmacology , Protein Kinase C/antagonists & inhibitors , Rabbits
10.
Foot Ankle Int ; 22(3): 203-8, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11310861

ABSTRACT

We retrospectively reviewed the results of a distal soft-tissue procedure and proximal crescentic osteotomy of the first metatarsal combined with a proximal shortening osteotomy of the second and/or third metatarsal. This was in patients who had hallux valgus with painful plantar callosities. The review covered seven years of procedures (1989-1996) in 12 patients (14 feet) averaging 53 years of age. Average follow-up was 52 months. All patients had pain at the first metatarsophalangeal joint and had metatarsalgia preoperatively. At follow-up, 11 feet had no pain at the first metatarsophalangeal joint, and three had some improvement of pain. Ten feet had no metatarsalgia, two had improvement of metatarsalgia, and two feet had transfer lesions postoperatively and required reoperation. The angle of hallux valgus averaged 40 degrees preoperatively and 13 degrees postoperatively. The intermetatarsal angle averaged 18 degrees preoperatively and 6 degrees postoperatively. Mean decreases in length of the second and third metatarsal after surgery were 5.4 mm and 4.8 mm, respectively. Our results suggested that this combined procedure for hallux valgus with painful plantar callosities may be successful, in carefully selected patients.


Subject(s)
Callosities/etiology , Callosities/surgery , Hallux Valgus/complications , Hallux Valgus/surgery , Metatarsal Bones/surgery , Osteotomy , Adult , Aged , Callosities/complications , Combined Modality Therapy , Female , Follow-Up Studies , Foot/surgery , Humans , Male , Metatarsus , Middle Aged , Osteotomy/methods , Pain/etiology , Pain Management , Recurrence , Reoperation , Retrospective Studies
11.
Jpn J Cancer Res ; 91(12): 1264-8, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11123425

ABSTRACT

Cancer cells express different levels of apoptosis-promoting Bax protein. The present study evaluated whether induction of Bax initiates apoptosis and whether Bax overexpression enhances apoptosis induced by several chemotherapeutic agents in DLD-1 colon cancer cells, which originally express a high level of endogenous Bax protein and a low level of Bcl-2 protein. To investigate these two points, parental DLD-1 cells were transfected with the Tet-On Bax induction system (pTet-On and pTRE-Bax plasmids), and stable transduced cells were obtained. Induction of Bax by the Tet-On system initiated cytochrome c release from mitochondria, caspase-3 activation, and apoptosis to some extent in DLD-1 cells. Apoptosis induced by a chemotherapeutic agent, 5-fluorouracil, mitomycin C, paclitaxel, doxorubicin, or cisplatin, was enhanced by Bax overexpression. These findings suggest that Bax-overexpression-based gene therapy combined with chemotherapy would be effective in the treatment of colon cancer.


Subject(s)
Antineoplastic Agents/toxicity , Apoptosis/physiology , Cytochrome c Group/metabolism , Mitochondria/metabolism , Proto-Oncogene Proteins c-bcl-2 , Proto-Oncogene Proteins/biosynthesis , Apoptosis/drug effects , Caspase 3 , Caspases/metabolism , Cisplatin/toxicity , Colonic Neoplasms , Doxorubicin/toxicity , Fluorouracil/toxicity , Humans , In Situ Nick-End Labeling , Kinetics , Mitomycin/toxicity , Paclitaxel/toxicity , Proto-Oncogene Proteins/genetics , Recombinant Proteins/biosynthesis , Transfection , Tumor Cells, Cultured , bcl-2-Associated X Protein
12.
Clin Orthop Relat Res ; (379): 209-17, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11039808

ABSTRACT

The results of a distal soft tissue procedure and a proximal metatarsal osteotomy in patients with symptomatic hallux valgus deformity were reviewed. The series consisted of 33 patients (47 feet; mean age of patients, 44 years). The average followup period was 48 months. At followup, 41 feet (29 patients, 85%) were free from pain at the first metatarsophalangeal joint. In six feet (four patients), the pain was improved but persisted. The mean hallux valgus angle was 38 degrees before surgery and 13.8 degrees after surgery. The mean intermetatarsal angle was 17.7 degrees before surgery and 7 degrees after surgery. The postoperative hallux valgus angle and intermetatarsal angle in patients who had pain at the first metatarsophalangeal joint after surgery were greater than those in patients without pain after surgery. This procedure corrects the hallux valgus deformity and relieves the symptoms, but careful attention should be paid to the surgical technique to obtain consistent and satisfactory results.


Subject(s)
Hallux Valgus/surgery , Metatarsus/surgery , Osteotomy , Adolescent , Adult , Aged , Female , Follow-Up Studies , Hallux Valgus/diagnostic imaging , Humans , Male , Metatarsophalangeal Joint/diagnostic imaging , Metatarsophalangeal Joint/surgery , Metatarsus/diagnostic imaging , Middle Aged , Osteotomy/methods , Pain , Radiography , Range of Motion, Articular
13.
Org Lett ; 2(14): 2015-7, 2000 Jul 13.
Article in English | MEDLINE | ID: mdl-10891218

ABSTRACT

A new aspect of commonly used BF(3).OEt(2) has been illuminated by successfully demonstrating the unique but highly stereoselective reactions of hydroxy carbonyl and dicarbonyl substrates. For example, treatment of gamma-hydroxy ketone 1c with BF(3).OEt(2)/Bu(3)SnH in CH(2)Cl(2) at -78 to -40 degrees C afforded the corresponding 1, 4-diol 2c with virtually complete diastereoselection, while use of TiCl(4) as a Lewis acid under similar reaction conditions caused a total lack of diol yield and selectivity (17%; 2c/3c = 1.2:1), accompanied by a significant formation of 2,3-disubstituted tetrahydrofuran 4 (44%).

14.
Foot Ankle Int ; 20(11): 714-20, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10582847

ABSTRACT

The palmaris longus tendon was used to reconstruct the anterior talofibular ligament (ATFL) in 27 ankles with chronic lateral instability. The mean age of the patients at surgery was 23 years, and the follow-up was more than 2 years. The functional evaluation showed excellent or good results in all ankles. Twenty-seven ankles were divided into two groups according to operative findings: group A consisted of 11 ankles with old isolated injury of the ATFL, and group B consisted of 16 ankles with old combined injuries of the ATFL and the calcaneofibular ligament. There were no significant differences in clinical results between group A and group B. The preoperative mean talar tilt angles on stress radiograph in group B were significantly larger than those in group A. At follow-up, there were no significant differences in the mean talar tilt angles between group A and group B. We demonstrate that reconstruction of the calcaneofibular ligament along with the ATFL is not necessary for patients with chronic combined lateral ligament instability.


Subject(s)
Ankle Joint , Ankle , Joint Instability/surgery , Ligaments, Articular/surgery , Tendons/surgery , Adolescent , Adult , Ankle Injuries/complications , Chronic Disease , Female , Follow-Up Studies , Humans , Joint Instability/pathology , Joint Instability/physiopathology , Male , Middle Aged
15.
Am J Physiol ; 277(4): H1369-74, 1999 10.
Article in English | MEDLINE | ID: mdl-10516171

ABSTRACT

Prostaglandin E(1) (PGE(1)) has cardioprotective effects on the ischemic-reperfused heart. To clarify the mechanisms underlying the protective action of PGE(1) on myocardium, we examined the effect of PGE(1) on the L-type Ca(2+) current (I(Ca)) using single atrial cells from rabbits. PGE(1) did not show a significant effect on basal I(Ca) but inhibited the I(Ca) prestimulated by isoproterenol (Iso, 30 nM). This inhibition was concentration dependent (EC(50) = 0.027 microM). Both sulprostone, a specific PGE receptor subtype (EP(1) and EP(3)) agonist, and 11-deoxy-PGE(1), an EP(3) agonist, inhibited the Iso-stimulated I(Ca), similar to PGE(1). Pretreatment with pertussis toxin (PTX) abolished the PGE(1) inhibition of I(Ca). Both the application of forskolin plus IBMX and intracellular dialysis with 8-bromoadenosine 3',5'-cyclic monophosphate eliminated the effect of PGE(1). PGE(1) did not show any further inhibition of I(Ca) when the effect of Iso was almost fully antagonized by acetylcholine. Methylene blue (guanylate cyclase inhibitor), KT-5823 (cGMP-dependent protein kinase inhibitor), and erythro-9-(2-hydroxy-3-nonyl)adenine (type II phosphodiesterase inhibitor) did not significantly change the inhibitory effect of PGE(1). These findings suggest that 1) PGE(1) inhibits Iso-stimulated I(Ca) by binding to the EP(3) receptor and 2) the PTX-sensitive and cAMP-dependent pathway is involved in the PGE(1) inhibition of I(Ca), but the nitric oxide-cGMP-dependent pathway is not. The PGE(1)-induced antiadrenergic effect shown in this study may contribute to the PGE(1) protection of myocardium against ischemia.


Subject(s)
Alprostadil/physiology , Calcium Channels, L-Type/physiology , Myocardium/metabolism , Receptors, Prostaglandin E/physiology , Adrenergic beta-Agonists/pharmacology , Animals , Isoproterenol/pharmacology , Myocardium/cytology , Protein Isoforms/physiology , Rabbits , Signal Transduction/physiology
16.
Cardiovasc Res ; 41(1): 166-74, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10325964

ABSTRACT

OBJECTIVE: Adenine compounds, including adenosine-5'-triphosphate (ATP) and adenosine (Ado), exert inhibitory effects on myocardium via P1 (subtype A1) purinoceptors. However, ATP per se is a potent activator of P2 purinoceptors. Our aim was to elucidate the respective roles of P1 and P2 purinoceptors in the actions of ATP on L-type calcium current (ICa) in rabbit atrial cells. METHODS AND RESULTS: A whole cell clamp technique was used to record ICa in single atrial cells from the rabbit heart. ATP (0.1 mumol/1-3 mmol/l) produced an inhibitory effect on ICa prestimulated by isoproterenol (ISO, 30 nmol/l), even in the presence of Ado (1 mmol/l). Both 1,3-dipropyl-8-cyclopentylxanthine (A1 blocker) and suramin (P2 blocker) partially blocked the ATP-induced inhibition of ICa, while their co-application nearly completely abolished the effect of ATP. ATP-gamma S (30 mumol/l) inhibited ISO-stimulated ICa significantly, and this inhibition was completely blocked by suramin. alpha, beta-Methylene-ADP, an inhibitor of hydrolysis of AMP to Ado, eliminated the suramin-resistant component of ICa inhibition by ATP. Pretreatment with pertussis toxin (PTX) abolished the ATP inhibition of ICa. Both intracellular dialysis with 8Br cAMP and the application of forskolin plus 3-isobutyl-1-methylxanthine also eliminated the effect of ATP. CONCLUSIONS: Both P1 and P2 purinoceptors are involved in the ATP inhibition of ISO-stimulated ICa in rabbit atrial cells. The P1 stimulation by ATP results from hydrolysis of ATP to Ado. Both the P2- and the P1-mediated effects of ATP and Ado, respectively. involve a PTX-sensitive and cAMP-dependent pathway.


Subject(s)
Adenosine Triphosphate/pharmacology , Calcium-Transporting ATPases/drug effects , Cyclic AMP/metabolism , Myocardium/metabolism , Potassium Channels, Voltage-Gated , Receptors, Purinergic P2/metabolism , 1-Methyl-3-isobutylxanthine/pharmacology , 5'-Nucleotidase/antagonists & inhibitors , 8-Bromo Cyclic Adenosine Monophosphate/pharmacology , Adenosine/pharmacology , Adenosine Diphosphate/analogs & derivatives , Adenosine Diphosphate/pharmacology , Adenosine Triphosphate/analogs & derivatives , Adrenergic beta-Agonists/pharmacology , Animals , Colforsin/pharmacology , Enzyme Inhibitors/pharmacology , Isoproterenol/pharmacology , Patch-Clamp Techniques , Pertussis Toxin , Potassium Channels/metabolism , Purinergic P1 Receptor Antagonists , Purinergic P2 Receptor Antagonists , Rabbits , Shal Potassium Channels , Suramin/pharmacology , Virulence Factors, Bordetella/pharmacology , Xanthines/pharmacology
18.
FEBS Lett ; 445(1): 87-91, 1999 Feb 19.
Article in English | MEDLINE | ID: mdl-10069379

ABSTRACT

We examined the effects of interferon-alpha on the ATP-sensitive K+ current (IK,ATP) in rabbit ventricular cells using the patch-clamp technique. IK,ATP was induced by NaCN. Whole-cell experiments indicated that interferon-alpha (5 x 10(2) - 2.4 x 10(4) U/ml) inhibited IK,ATP in a concentration-dependent manner (60.7+/-7.5% with 2.4 x 10(4) U/ml). In cell-attached configuration, interferon-alpha (2.4 x 10(4) U/ml) applied to the external solution also inhibited the activity of the single ATP-sensitive K+ (KATP) channel by 56.0+/-5.8% without affecting the single channel conductance. The inhibitory effect of IK,ATP by interferon-alpha was blocked by genistein and herbimycin A, tyrosine kinase inhibitors, but was not affected by N-(2-metylpiperazyl)-5-isoquinolinesulfoamide (H-7), an inhibitor of protein kinase C and cAMP-dependent protein kinase. These findings suggest that interferon-alpha inhibits the cardiac KATP channel through the activation of tyrosine kinase. The tyrosine kinase-mediated inhibition of IK,ATP by cytokines may aggravate cell damage during myocardial ischemia.


Subject(s)
Adenosine Triphosphate/metabolism , Interferon-alpha/metabolism , Potassium Channels/physiology , Protein-Tyrosine Kinases/metabolism , Animals , Benzoquinones , Enzyme Inhibitors/pharmacology , Genistein/pharmacology , Heart Ventricles/cytology , Interferon-alpha/pharmacology , Lactams, Macrocyclic , Potassium Channel Blockers , Protein-Tyrosine Kinases/antagonists & inhibitors , Quinones/pharmacology , Rabbits , Rifabutin/analogs & derivatives
19.
J Pharmacol Exp Ther ; 287(1): 293-300, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9765349

ABSTRACT

We examined the blocking effects of terfenadine, an antihistaminic agent, on the ATP-sensitive K+ current (IK,ATP) in rabbit ventricular cells. IK,ATP was induced by cromakalim or NaCN. Terfenadine blocked the IK,ATP with an IC50 of 1.7 microM at -10 mV. This blockage was voltage dependent; depolarization induced a stronger blockage. According to the transmembrane electrical field model, terfenadine interacts with the site located 15 to 18% from the cytoplasmic membrane surface. In line with the assumption that the binding site is near the cytoplasmic surface, terfenadine applied to the cytoplasmic solution potently inhibited the single-channel activity for IK,ATP in the inside-out configuration (IC50 0.19 microM). In contrast, terfenadine applied to the external solution did not affect the channel activity in the cell-attached configuration, but inhibited it when applied into the pipette. The inhibition of the single channels by terfenadine was accompanied by flickering of the channels. These findings suggest that 1) terfenadine blocks the ATP-sensitive K+ channel in the open state, 2) the binding site is near the internal membrane surface and 3) terfenadine is poorly diffusible into the lipid biomembrane and accesses the binding site via the hydrophilic pathway. Terfenadine also inhibited the transient outward K+ current, inward rectifier K+ current and E4031-sensitive rectifier K+ current. However, the inhibition of these repolarization currents by terfenadine at 1 microM was not sufficient to prolong the action potential duration significantly. Whereas, terfenadine (1 microM) prolonged the action potential duration which had been shortened by cromakalim. Terfenadine may modify the ischemia-induced arrhythmias by blocking IK,ATP.


Subject(s)
Adenosine Triphosphate/pharmacology , Heart Ventricles/drug effects , Histamine H1 Antagonists/pharmacology , Potassium Channel Blockers , Terfenadine/pharmacology , Action Potentials/drug effects , Animals , Heart Ventricles/cytology , Rabbits
20.
Biochem Mol Biol Int ; 45(2): 289-301, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9678250

ABSTRACT

Human pepsinogen (PG) A and C were cloned in Escherichia coli, but the levels of expression were low and unstable. When there were fused to maltose-binding protein (MBP), the fusion proteins (MBP-PGA and MBP-PGC) were expressed as the major products. Although these fused products were almost totally recovered from the insoluble fraction, the renaturation and purification procedures were easy and simple. MBP-PGA and the PGA segment obtained by factor Xa digestion (designated as r-PGA) possessed proteolytic activities equivalent to native PGA purified from gastric tissue (t-PGA). For PGCs (MBP-PGC, r-PGC and t-PGC) also, the specific activities were almost the same. However, the activities of PGCs were about 3- to 4-hold higher than those of PGAs. In PGA and PGC immunoassay systems, r-PGs (r-PGA and r-PGC) and the EIA kit standard PGs (gastric mucosal PGs) exhibited a good correlation. From these results, r-PGs would seem to be applicable as assay standards without compromising the sensitivity of the immunoassay systems.


Subject(s)
ATP-Binding Cassette Transporters , Escherichia coli Proteins , Immunoassay/methods , Monosaccharide Transport Proteins , Pepsinogens/isolation & purification , Pepsinogens/metabolism , Antibodies, Monoclonal/metabolism , Carrier Proteins , Cloning, Molecular , DNA, Complementary , Escherichia coli/genetics , Humans , Hydrogen-Ion Concentration , Maltose-Binding Proteins , Pepsinogens/genetics , Recombinant Fusion Proteins/isolation & purification , Recombinant Fusion Proteins/metabolism , Reference Standards
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