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R Shimizu

Publications and source records attributed to R Shimizu.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Comparison of five patient-controlled analgesia drug delivery devices].

We report the performance and our impression of five patient-controlled analgesia (PCA) drug delivery devices commercially available; Atom PCA Pump 500, AP-II, Deltec CADD-PCA 5800, Sabratek 6060 and Verifuse. Each of these devices has unique features for PCA. However, these devices still leave some room for improvement. Especially, we hope that future devices will be lighter to carry and use dry batteries more economically. In order to use these devices effectively for the management of pain, it is important to understand their characteristics.

Analgesia, Patient-Controlled↗
PubMed1999

3D-pharmacophore analyses of aldose reductase inhibitory spiroquinazolinones.

In order to get an insight for designing novel inhibitors of aldose reductase, we analyzed relationships between structures of spiroquinazolinones and their inhibitory activities against rabbit aldose reductase by comparative molecular field analysis and molecular modeling of the enzyme-inhibitor complex. It was revealed that the following interactions were operative for the enhancement of inhibitory activity; 1) the hydrophobic interaction between substituents at the 6'- and 7'-position of quinazolinone and the hydrophobic residues such as Trp20, Val47, Tyr48, Tyr121 and Phe122; 2) the electrostatic interaction formed between electronegative substituents at the 6'-position and the side chain of Gln49; 3) the complementary fit of sterically small 6'-substituents to the active site.

Aldehyde Reductase↗
PubMed1998

Design of novel tripeptides with macrophage migration-enhancing activity.

A new approach to the generation of biologically active peptides from non-peptide lead was demonstrated. C,N-termini protected Phe-Phe-His derivatives possessing macrophage migration-enhancing activity were designed on the basis of the structure of imidazoline derivative 1, and these structure-activity relationships were also described.

Cell Movement↗
PubMed1998

Rapid purification and molecular modeling of AaIT peptides from venom of Androctonus australis.

As recombinant viruses expressing scorpion toxins are moving closer toward the market, it is important to obtain large amounts of pure toxin for biochemical characterization and the evaluation of biological activity in nontarget organisms. In the past, we purified a large amount of Androctonus australis anti-insect toxin (AaIT) present in the venom of A. australis with an analytical reversed-phase column by repeated runs of crude sample. We now report 20 times improved efficiency and speed of the purification by employing a preparative reversed-phase column. In just two consecutive HPLC steps, almost 1 mg of AaIT was obtained from 70 mg crude venom. Furthermore, additional AaIT was obtained from side fractions in a second HPLC run. Recently discovered insect selective toxin, AaIT5, was isolated simultaneously from the same venom batch. It shows different biological toxicity symptoms than the known excitatory and depressant insect toxins. AaIT5 gave 100% mortality with a dose of less than 1.3 micrograms against fourth-instar tobacco budworms Heliothis virescens 24 h after injection. During the purification process, we implemented mass spectrometry in addition to bioassays to monitor the presence of AaIT and AaIT5 in the HPLC fractions. Mass spectrometric screening can unambiguously follow the purification process and can greatly facilitate and expedite the downstream purification of AaIT and AaIT5 eliminating the number of bioassays required. Further, electrospray ionization was compared with matrix-assisted desorption/ionization and evaluated as a method of choice for mass spectrometric characterization of fractions from the venom purification for it provided higher mass accuracy and relative quantitation capability. Molecular models were built for AaIT5, excitatory toxin AaIT4, and depressant toxin LqhIT2. Three-dimensional structure of AaIT5 was compared with structures of the other two toxins, suggesting that AaIT5 is similar to depressant toxins.

Amino Acid Sequence↗
PubMed1998

Quantitative structure-activity analyses of novel hydroxyphenylurea derivatives as antioxidants.

A series of substituted hydroxyphenylureas was synthesized, the chemical structure of which was designed based on structures of natural antioxidants, vitamin E (alpha-tocopherol) and uric acid. They exhibited high inhibitory activity against lipid peroxidation. In order to gain an insight into the mechanism of the inhibition reaction, we analyzed their structure-activity relationships quantitatively. Electronic and steric effects of substituents on the phenolic hydroxyl group were shown to be of importance in governing the inhibitory potency. An increase in the electron donating property of substituents toward the phenolic hydroxyl group enhanced the antioxidative activity by the stabilization of an electron-deficient radical-type transition state. The steric shielding by ortho-substituents stabilized the phenoxy radicals formed following the transition state. Derivatives having the carboxyl group were only weakly active presumably because of an intermolecular ion-dipole interaction of the phenolic hydroxyl group with the carboxylate anion which could retard the formation of the transition state.

Animals↗
PubMed1998

Thoracic and lumbar extradural structure examined by extraduroscope.

We examined the extradural space using a flexible extraduroscope in 113 patients undergoing extradural anaesthesia. Patients were classified into two groups to receive either thoracic or lumbar extradural anaesthesia as needed for perioperative analgesia. The extraduroscopy showed that the thoracic extradural space becomes widely patent after injecting a given amount of air and that the amount of fatty and fibrous connective tissue is less in the thoracic extradural space compared with the lumbar extradural space. We suggest that differences between the structure of these two vertebral regions may affect the spread of local anaesthetics in the extradural space.

Adipose Tissue↗
PubMed1998

Effects of lightwand (Trachlight) compared with direct laryngoscopy on circulatory responses to tracheal intubation.

We compared the effects of the lightwand technique on circulatory responses to tracheal intubation with those of direct-vision laryngoscopy. Forty adult patients received propofol and vecuronium, and their lungs were ventilated for 2 min via a mask with 5% sevoflurane in oxygen, after which the trachea was intubated orally using either the lightwand (Trachlight, n = 20) or the Macintosh laryngoscope (n = 20). Maximum mean arterial pressure changes did not differ between groups during (lightwand group, 25 (SD 21) mm Hg vs laryngoscopy group, 23 (19) mm Hg) and after (21 (24) mm Hg vs 21 (16) mm Hg) tracheal intubation. Maximum heart rate changes were similar for groups during (16 (14) beat min-1 vs 16 (15) beat min-1) and after (2 (11) beat min-1 vs 7 (19) beat min-1) tracheal intubation. There were no differences between the lightwand technique and direct-vision laryngoscopy in changes in mean arterial pressure and heart rate during and after tracheal intubation. We conclude that the effects of the lightwand technique on circulatory responses to tracheal intubation were similar to those of direct-vision laryngoscopy.

Adult↗
PubMed1998

Dose-related cardiovascular effects of amrinone and epinephrine in reversing bupivacaine-induced cardiovascular depression.

BACKGROUND: To ascertain the efficacy of amrinone and epinephrine in reversing bupivacaine-induced cardiovascular depression, we investigated the time course of recovery of cardiac function with 3 doses of both agents after bupivacaine administration. METHODS: In sevoflurane-anaesthetized dogs, bupivacaine was infused intravenously at 1 mg.kg-1.min-1 until mean arterial pressure fell to 60 mmHg or less. The 3 doses of amrinone (1, 2, and 4 mg.kg-1) or the 3 doses of epinephrine (2, 5, and 10 micrograms.kg-1) were administered as a bolus in randomized order in each dog. RESULTS: Amrinone improved maximum left ventricular dP/dt, a time constant of left ventricular isovolemic relaxation and cardiac index persistently and dose-relatedly. Amrinone increased heart rate and decreased left ventricular end-diastolic pressure and systemic vascular resistance index. Amrinone at 1 and 2 mg.kg-1 significantly increased mean arterial pressure, but amrinone at 4 mg.kg-1 did not. Epinephrine increased mean arterial pressure, maximum left ventricular dP/dt, and systemic vascular resistance dose-relatedly. The duration of action of epinephrine, peaking at 1 min and subsequently decreasing by 10 min after administration, did not differ among the groups. Epinephrine at all doses failed to improve a time constant of left ventricular isovolemic relaxation and cardiac index. ECG evidence of serious ventricular dysrhythmias was seen in 1 out of 6 dogs after administrating each dose of amrinone and in 3, 3 and 5 out of 6 dogs after administrating 2, 5 and 10 micrograms.kg-1 of epinephrine, respectively. CONCLUSION: Bolus amrinone may have a certain efficacy in reversing bupivacaine-induced cardiovascular depression, and improving cardiac contractility and relaxation dose-relatedly. In contrast to amrinone, bolus epinephrine remains indispensable for resuscitation, causing a rapid, massive, transient and dose-related rise in blood pressure. However, the use of amrinone may be limited predominantly by a decrease in systemic vascular resistance, while the use of epinephrine may be limited predominantly by the generation of serious ventricular dysrhythmias and lack of effectiveness on cardiac index and on cardiac relaxation.

Amrinone↗
PubMed1998

Phylogenetic analysis of Atractylodes plants based on chloroplast trnK sequence.

The phylogenetic relationship of Atractylodes lancea, A. chinensis, A. koreana, A. ovata and A. japonica were analyzed by comparing the 2.6 kb sequence in a chloroplast gene trnK encoding tRNALys (UUU). The dried rhizomes of the former three species have been used as the crude drug "So-jutsu" and those of the latter two as "Byaku-jutsu" in Chinese and Japanese traditional medicine ("Kampo-medicine"). The trnK phylogenetic tree revealed that A. ovata is an outgroup of the five Atractylodes species examined and that A. japonica and A. lancea are most closely related. PCR amplification of trnK with HinfI digestion provided us with a simple method to distinguish A. ovata from other Atractylodes species at the molecular level.

Base Sequence↗
PubMed1998

[Retrospective analysis of elderly patients > or = 60 years of age with acute leukemia].

A retrospective analysis was performed on 76 consecutive elderly patients with acute leukemia aged 60 years or more (48 men, 28 women). Forty patients were 60-69 years old, 28 were 70-79 years old and 8 were > or = 80 years old. There were 55 patients with acute myelogenous leukemia (AML), 13 acute lymphoblastic leukemia (ALL) and 8 AML from myelodysplastic syndrome (MDS/AML). Patients were treated with the JALSG protocol, CAG regimen, or low-dose Ara-C regimen for AML, and DVP/M-CHOP protocol for ALL. The complete remission (CR) rates were 52.7% (29 of 55) in AML, 61.5% (8 of 13) in ALL, and 0% in MDS/AML. The median CR durations were 226, 85, 0 days, and the median survivals were 204, 177, 99 days, respectively. CR rates were 65.3% for the JALSG protocol, 62.5% for the CAG regimen and 25.0% for low-dose Ara-C regimen. According to age, CR was obtained 62.5% in patients aged 60-69 years and 33.3% in patients over 70 years old. Our results indicated that patients aged 60-69 years should be treated with intensive chemotherapy.

Aclarubicin↗
PubMed1998

[Tracheal intubation for emergent tracheostomy in a patient complicated with tracheal stenosis].

We report the management of anesthesia for emergent tracheostomy in a patient with severe tracheal stenosis. A 63-year-old male was scheduled for an emergency tracheostomy for severe tracheal stenosis due to the invasion of a thyroid cancer. A preoperative neck CT revealed the tracheal stenosis, extending from 1-2 cm below the vocal cord to the upper end of the sternum. The narrowest caliber was about 7 mm in transverse diameter. Moreover, the cancer was suspected to have a bleeding tendency. General anesthesia with endotracheal intubation was considered necessary to provide an open airway during tracheostomy. Anesthesia was induced with thiopental, and a 6.0 mm endotracheal tube with cuff was successfully introduced with a balloon introducer (AIRGUID E) using suxamethonium. We were able to perform tracheostomy uneventfully.

Anesthesia, General↗
PubMed1998

[Sevoflurane anesthesia for myotonic dystrophy].

We successfully anesthetized a 14-year-old boy with myotonic dystrophy for orthopedic surgery using sevoflurane. Sevoflurane enabled anesthetic induction and tracheal intubation without intravenous anesthetics and muscle relaxants. Sevoflurane also provided stable anesthetic maintenance without intravenous anesthetics. The patient showed rapid anesthetic recovery and adequate spontaneous breathing. We conclude that sevoflurane is a useful anesthetic for patients with myotonic dystrophy.

Adolescent↗
PubMed1997

In vitro development of erythroid and megakaryocytic cells from a UT-7 subline, UT-7/GM.

UT-7 is a human megakaryoblastic leukemia cell line with absolute dependence on interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or erythropoietin (EPO) for growth and survival. We isolated a novel subline, UT-7/GM after long-term culture of UT-7 with GM-CSF. The hemoglobin concentration and gamma-globin and EPO-receptor mRNA levels were significantly higher in EPO-treated UT-7/GM cells than in untreated cells. In contrast, the platelet factor 4 and glycoprotein IIb mRNA levels were much higher in thrombopoietin (TPO)-treated UT-7/GM cells than in untreated cells. Some TPO-treated cells had morphologically mature megakaryocytic characteristics such as a developed demarcation membrane in the cytoplasm and multilobular nuclei. These findings indicate that UT-7/GM is a bipotential cell line that can be induced to differentiate into erythroid and megakaryocytic lineages by EPO and TPO, respectively. Moreover, a minority of UT-7/GM cells acquired a high hemoglobin concentration by treatment with TPO, suggesting that TPO in part induced the erythroid differentiation of the UT-7/GM cells. Interestingly, GM-CSF inhibited the EPO- or TPO-induced erythroid differentiation and the TPO-induced megakaryocytic differentiation of UT-7/GM cells. These results support the hypothesis that cytokines influence the programming of gene expression required for lineage commitment or differentiation.

Cell Differentiation↗
PubMed1997

Resistance to IL-1 anti-proliferative effect, accompanied by characteristics of advanced melanoma, permits invasion of human melanoma cells in vitro, but not metastasis in the nude mouse.

We reported earlier that IL-1 inhibits the growth of human melanoma cells (A375-6), and that these cells become resistant to IL-1 after prolonged periods of culture. The resistant cells constitutively produce IL-alpha and IL-6 with IL-6 production was induced by endogenous IL-1 in an autocrine manner. The cells are also resistant to IL-6 anti-proliferative effects. In the present study, we show that the resistant clones exhibited up-regulated expression of intercellular-adhesion molecule 1 (ICAM-1) and vitronectin receptor (integrin alpha(v)beta3) when compared with the IL-1-sensitive clone, A375-6. Moreover, these IL-1-resistant clones exhibited many other metastatic characteristics, such as expression of IL-8 mRNA, production of matrix metalloproteinases (MMP-2 and MMP-9), and augmented invasion activity. However, contrary to our expectations, the IL-1-resistant cells did not exhibit experimental metastasis in a nude-mouse model, similarly to the IL-1-sensitive parental A375-6 cell line. In contrast, the highly metastatic clone A375-SM exhibited alpha(v)beta3 expression at a level comparable to that of the IL-1-resistant cells, but expressed low or no ICAM-1, metalloproteinase and displayed little in vitro invasion activity. These results show that the metastatic characteristics of IL-1-resistant cells are not sufficient to produce metastasis in vivo and suggest that these resistant clones may provide a good model system for characterizing the molecular mechanisms of metastasis.

Animals↗
PubMed1997

Identification of functional domains of the human thrombopoietin receptor required for growth and differentiation of megakaryocytic cells.

To identify the functional domains of the human thrombopoietin (TPO) receptor essential for proliferation and megakaryocytic differentiation, we introduced human wild type c-mpl cDNA and deletion mutants of c-mpl cDNA into the human erythropoietin (EPO)-dependent cell line UT-7/EPO that does not express endogenous c-Mpl. TPO induced the proliferation and megakaryocytic differentiation of UT-7/EPO expressing wild type c-Mpl, as evidenced by increased levels of the CD41 antigen specific for cells of the megakaryocytic lineage and by changes in morphology. Mutational analysis of the cytoplasmic domain of c-Mpl identified four functional regions: (a) two C-terminal regions (amino acids 575-586 and 615-630) containing a domain essential for cell proliferation and megakaryocytic differentiation but not for DNA synthesis; (b) a region (amino acids 587-614) containing a negative domain for TPO-induced cell proliferation and megakaryocytic differentiation; and (c) a region (amino acids 565-574) including a box2 motif that is required for DNA synthesis. These deletion mutants will provide useful materials for analyzing the signals specific for TPO-induced proliferation and megakaryocytic differentiation.

Cell Differentiation↗
PubMed1997

Protein kinase C and c-myc gene activation pathways in thrombopoietin signal transduction.

Thrombopoietin (TPO) is the major regulator of the proliferation and differentiation of megakaryocyte precursors through interaction with its receptor encoded by the c-mpl protooncogene. We established the human TPO-dependent leukemia cell line, UT-7/TPO (Blood 87, 4552, 1996). In these cells, TPO activated protein kinase C (PKC) in a time dependent manner. Subsequently, the c-myc gene was transiently induced to a maximal level 60-90 minutes after TPO exposure. In addition, we found that stimulating UT-7/TPO cells with TPO rapidly induces the significant accumulation of inositol 1, 4, 5-trisphosphate (Ins-P3), leading to the mobilization of calcium from intracellular stores. Taken together, the activation of PKC and subsequent c-myc gene induction are involved in the TPO-induced cellular response(s), presumably through the activation of PLC.

Calcium↗