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Biomedical subjects

Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 919 records · Page 51Linked to original sources

[EEG pattern during total intravenous anesthesia with droperidol, fentanyl and ketamine].

We evaluated EEG pattern during total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK). Four surgical patients, ranged in age from 35 to 43, were the subjects of this study. Two male underwent oral or orthopedic surgery and the other two female patients underwent gynecological surgery. They were all free from hepato-renal dysfunction and central nervous system disorders. For the induction of anesthesia, droperidol 0.06-0.1 ml.kg-1, fentanyl 2-4 micrograms.kg-1, and ketamine 1.0-1.5 mg.kg-1 were slowly administered intravenously. A total dose of 5-15 micrograms.kg-1 of fentanyl was given intravenously with continuous infusion of ketamine 2 mg.kg-1.h-1 during the surgical procedure. The total amounts of fentanyl and ketamine administered were 4.9-22.2 micrograms.kg-1 and 240-340 mg.kg-1, respectively. We used HZI'Brain Function Monitoring system to evaluate their EEG patterns. When adequate depth of anesthesia was obtained as clinically evaluated by vital signs, theta wave pattern was dominant on the EEG tracings in any of these patients. DFK anesthesia would provide a stable anesthetic course, if those drugs are administered adequately considering vital signs including systemic blood pressure, heart rate, lacrimation and involuntary muscle movements of the face and extremities.

Adult↗

[A comparative study of VEPA and ACOMEP-BD regimen for the patients with non-Hodgkin's lymphoma].

Between 1981 and 1990, ACOMEP-BD regimen (adriamycin, cyclophosphamide, vincristine, methotrexate, etoposide, prednisolone, bleomycin, dacarbazine) was compared with VEPA regimen (vincristine, cyclophosphamide, prednisolone, adriamycin) in 66 newly diagnosed patients younger than 65 of age, with non-Hodgkin's lymphoma (NHL). The median age of the patients was 47.5 years (range 22-64 years), 43 males and 23 females. One patients were in stage I, 6 were in II, 27 were in III, 32 were in IV. Twenty-seven patients received VEPA and 39 received ACOMEP-BD. The therapeutic results of 66 patients with ACOMEP-BD or VEPA were as follows: complete remission (CR) rate of 54% and 48%; relapse rate of 29% and 77%; CR duration of 2-34 months (mean: 22 months) and 2-74 months (16 months); freedom-from-relapse survival (at 3 years) of 71% and 38%; and overall survival (at 4 years) of 62% and 26%, respectively. In these results, only relapse rate was significant and the others were not. Prognostic factors were performance status (PS) and lactate dehydrogenase level for ACOMEP-BD, and PS and marrow involvement for VEPA. Received dose intensity was 0.85 in ACOMP-BD and 0.41 in VEPA. It was expected that outcome of patients with NHL can be improved by increasing dose intensity.

Adult↗

Apolipoprotein E enhances lipid exchange between lipoproteins mediated by cholesteryl ester transfer protein.

The direct effect of apolipoprotein (apo) E on cholesteryl ester transfer protein (CETP) activity was studied using lipoproteins from a subject with apoE deficiency (Atherosclerosis. 1991. 88: 15-20) as a model system. The transfer of cholesteryl ester (CE) from discoidal bilayer particles (DBP) to very low density lipoprotein (VLDL) was enhanced by incorporation of apoE into VLDL. This enhancement was induced only in the presence of CETP activity. Moreover, after incubation of CETP with VLDL, CETP activity and immunoreactivity were coeluted with apoE-incorporated VLDL (E-VLDL) on a gel filtration column (Sephadex G-150), but there was little CETP activity and immunoreactivity with apoE-free VLDL (C-VLDL), suggesting that E-VLDL had higher affinity for CETP compared to C-VLDL. The supplementation of the apoE-deficient serum with apoE enhanced the CETP-mediated changes of amount of CE and triglyceride (TG) in the high density lipoprotein (HDL) fraction, which were completely inhibited by the addition of the monoclonal antibody against CETP that blocks CETP activity. Our results suggest that 1) apoE enhances the cholesteryl ester and triglyceride transfer between VLDL and HDL via cholesteryl ester transfer protein, and 2) this effect of apoE may be mediated by enhancing the affinity of CETP for VLDL.

Antibodies, Monoclonal↗

[Postoperative apnea in preterm infants after inguinal herniorrhaphy].

Preterm infants may become apneic during immediate postoperative period. We studied prospectively postoperative apneic attack in 167 preterm infants after inguinal herniorrhaphy with nitrous oxide-halothane anesthesia. Their mean gestational age was 30 +/- 3 weeks. The mean postnatal age at operation was 14 weeks. The post-conceptual age varied between 36 and 56 weeks. The mean birth weight was 1351 +/- 395 kg. Although many of them had a risk factor of postoperative apneic attack, i.e.a young post-conceptual age (less than 41 weeks), a light weight at operation (below 3000g), only one infant who had received emergency operation had an episode of apneic attack up to 2 postoperative days. For preventing postoperative apneic attack in preterm infants after inguinal hernia, we recommend the use of halothane anesthesia and the attention until a complete awakening.

Apnea↗

[Clinical study of total intravenous anesthesia with droperidol, fentanyl and ketamine--effects of nicardipine, diltiazem and nifedipine on intraoperative hypertension].

Effects of Ca ion channel blockers, nicardipine, diltiazem and nifedipine on intraoperative hypertension were evaluated clinically in ninety surgical patients who received various surgical procedures under total intravenous anesthesia with droperidol, fentanyl and ketamine. When the systemic blood pressure exceeded 160 mmHg systolic at least for ten minutes, even though they received a total dose of 10-15 micrograms.kg-1 of fentanyl, one of the following three antihypertension drugs was administered:nicardipine 0.5-1.0 micrograms i.v., diltiazem 5-10 mg i.v. and nifedipine 5-10 mg intranasally. The effects were evaluated by measuring the systemic blood pressure, heart rate and rate pressure product, before the administration as well as 5, 15, 20 and 30 minutes after the administration. Following the injection of the drug a significant 10-20% reduction in the mean systemic blood pressure was observed in the nifedipine group, while less decrease was observed in the diltiazem and nicardipine groups. The mean heart rate in the nifedipine group increased slightly, while a slight decreases was observed in the other two groups. Therefore the rate pressure product was reduced significantly in three groups, but there was no significant difference among them. No adverse episodes such as ischemic changes on E.K.G. and deterioration of the cardiovascular system were encountered in any patients. We conclude that any of these drugs, particularly nifedipine would be appropriate to control hypertension during total intravenous anesthesia with droperidol, fentanyl and ketamine.

Anesthesia, Intravenous↗

[Plasma levels of isosorbide dinitrate and its metabolites during intravenous infusion in surgical patients--effect of preoperative administration of isosorbide dinitrate].

Nineteen patients with ischemic heart disease were studied to determine plasma levels of isosorbide dinitrate (ISDN) and its metabolites, isosorbide-2-mononitrate (2-ISMN) and isosorbide-5-mononitrate (5-ISMN) for 6 hrs during intravenous administration of ISDN, using gas chromatography. Differences in plasma levels of these substances were also evaluated in patients with or without preanesthetic medication of ISDN. These patients ranging in ages from 42 to 80 years were administered ISDN intravenously at a rate of 1 micrograms.kg-1 x min-1 during anesthesia and surgery. Preanesthetic administration of ISDN consisted of transdermal application of 40 mg dose. Surgery included gastrectomy, pneumonectomy, extended cholecystectomy, radical mastectomy and so on under either enflurane anesthesia or neuroleptanesthesia. Plasma ISDN levels increased and reached a plateau 3 hrs after the start of intravenous infusion of ISDN in patients of both groups. Plasma 2-ISMN levels increased gradually and reached a plateau 5 hrs after the commencement of intravenous administration of ISDN in patients of both groups. Plasma 5-ISMN levels increased gradually reaching the peak 6 hrs after the start of intravenous infusion of ISDN in both groups. Plasma ISDN, 2-ISMN and 5-ISMN levels were slightly higher in patients who received preanesthetic ISDN than in those who did not receive preanesthetic ISDN. However, there were no statistical differences in plasma ISDN or 2-ISMN levels between the groups except prior to the infusion. On the contrary, plasma 5-ISMN levels were significantly higher in patients who received preanesthetic ISDN than in those who did not receive preanesthetic ISDN for 3 hrs after the start of the infusion.

Adult↗

Predominant expression of nPKC eta, a Ca(2+)-independent isoform of protein kinase C in epithelial tissues, in association with epithelial differentiation.

Of the nine known members of the protein kinase C (PKC) family, we found that novel (n-) PKC eta, a newly isolated Ca(2+)-independent isoform, was expressed at the highest level in the epidermis of mouse skin and epithelia of the digestive and respiratory tracts including the tongue, esophagus, forestomach, glandular stomach, intestine, colon, trachea, and bronchus. Expression of nPKC eta mRNA in these epithelial tissues was 3-10 times that in the brain and was especially high in squamous epithelium. Two other PKC isoforms, conventional (c-) PKC alpha and nPKC delta, were also expressed in these epithelial tissues, but no cPKC gamma was detected. In situ hybridization and immunohistochemical analyses demonstrated the localization of nPKC eta in suprabasal layers of the skin, tongue, esophagus, and forestomach. In the intestine, it was expressed in the epithelial cells of villi, but not of crypts. In the lung, only bronchial epithelium expressed nPKC eta. The localization of nPKC eta in differentiating or differentiated epithelial cells, rather than in proliferating basal cells, suggests the involvement of nPKC eta in epithelial differentiation.

Amino Acid Sequence↗

[A case report of total intravenous anesthesia for renal transplantation].

A 20-year-old female patient with chronic renal failure received renal transplantation under total intravenous anesthesia with droperidol, fentanyl and ketamine. Anesthesia was induced with droperidol 12.5 mg, fentanyl 100 micrograms, ketamine 100 mg and vecuronium bromide 5 mg, and maintained with fentanyl and ketamine. Ketamine was given continuously at a rate of 2.0 mg.kg-1.h-1. After the renal artery and vein of the donor kidney were anastomosed with the patient's internal iliac artery and vein, the urine output of 7.7 ml.min-1 was obtained. The patient recovered from anesthesia smoothly and her postoperative course was uneventful. Although plasma epinephrine, cortisol and ADH levels showed significant changes during anesthesia mainly due to surgical stress, they returned to normal values after the end of operation. We conclude that this method of anesthesia would be a choice for renal transplantation.

Adult↗

[Anesthetic experience of emergency cesarean section for a patient with myotonic dystrophy].

We report an anesthetic experience of a 28-year-old female patient complicated with myotonic dystrophy who underwent emergency Cesarean section due to threatened abortion. Anesthesia was induced with intravenous thiopental followed by topical spray of 4% lidocaine 5 ml to intubate trachea and maintained with neuroleptanesthesia with droperidol, fentanyl and nitrous oxide in oxygen. No muscle relaxant was used. The course of anesthesia and emergence from anesthesia were uneventful. However, the female infant, with Apgar score of 1 point at five minutes after delivery, died due to multiple organ failure three weeks after the delivery. Anesthetic management of a patient with myotonic dystrophy was also discussed with a literature review.

Abortion, Threatened↗

[Applicability to exercise test of thermodilution technique for right ventricular ejection fraction].

To assess the reliability of right ventricular ejection fraction (RVEF) during exercise measured by thermodilution technique using a modified Swan-Gantz catheter with a fast-response thermister, we measured RVEF under several conditions in 19 patients with cardiac disease. Measurements were repeated 5 times in each condition, and average RVEF and coefficient of variation (CV) were evaluated. 1) Injectate volume did not affect RVEF and CV. 2) A reduction in RVEF occurred with the thermister moved from proximal portion to distal portion within the pulmonary artery. 3) There were no differences in measurements of RVEF and CV between those during spontaneous breathing and those during apnea. 4) Postural change from supine to sitting decreased RVEF (38 +/- 8 to 35 +/- 9%; p < 0.05) and increased CV (7 +/- 2 to 13 +/- 5%). 5) Exercise increased RVEF (35 +/- 9 to 37 +/- 10%; p < 0.05) but did not change CV (13 +/- 5 vs 13 +/- 5%) compared with rest in the sitting position. 6) Cardiac rhythm (sinus vs atrial fibrillation) did not affect CV. 7) Average value of RVEF and CV during exercise were not different among 3, 4, 5 times repeated measurements. We considered that thermodilution technique for RVEF was applicable to exercise test, and 3 measurements were enough to determine the average value of RVEF during exercise.

Adult↗

Differentiation-inducing activity of retinoic acid isomers and their oxidized analogs on human promyelocytic leukemia HL-60 cells.

Retinoidal activity of retinoic acid isomers [all-trans-retinoic acid (ATRA), 9-cis-retinoic acid (9CRA) and 13-cis-retinoic acid (13CRA)] and their oxidized derivatives [19-hydroxy and 19-oxo derivatives of ATRA (19-hydroxy-ATRA and 19-oxo-ATRA), 19-oxo derivative of 9CRA (19-oxo-9CRA), and 19-hydroxy derivative of 13CRA (19-hydroxy-13CRA)] was evaluated by means of a human promyelocytic leukemia HL-60 cell differentiation induction assay. All the compounds examined showed this activity with ED50 values of 2-30 nM, which are in accordance with their binding activity to nuclear retinoic acid receptors (RARs).

Binding, Competitive↗

Role of acetylcholinesterase in airway epithelium-mediated inhibition of acetylcholine-induced contraction of guinea-pig isolated trachea.

To seek evidence for the involvement of acetylcholinesterase activity in the modulatory influence of the airway epithelium, we examined responses to acetylcholine (ACh), bethanechol, histamine or KCl in isolated epithelium-intact and epithelium-denuded guinea-pig trachealis preparations. The concentration-response curves to ACh were shifted 26-fold to the left by epithelial denudation but the contractile response to KCl was not altered. The response to histamine in epithelium-denuded preparations increased 4-fold with no attenuation in the presence of physostigmine (30 nM). Physostigmine (30 nM) potentiated the response to ACh in epithelium-intact tissues more (about 26-fold) than in epithelium-denuded tissues (about 3.5-fold). Thus, in the presence of physostigmine removing the epithelium had only a slight effect (not statistically significant) on the potency of ACh to contract the trachea. Removing the epithelium had no effect on the potency of bethanechol, a muscarinic receptor agonist that is not a substrate for cholinesterases. Physostigmine itself contracted the trachealis muscle but the pD2 values and maximum responses in epithelium-intact and denuded preparations were not significantly different. The frequency-response curves to electrical field-stimulated cholinergic contractions were unaffected by removing the epithelium. In conclusion, the principal mechanism by which the epithelium inhibits contraction of guinea-pig trachea to exogenously applied ACh is via epithelium-derived acetylcholinesterase activity.

Acetylcholine↗

Stabilization of a protein by removal of unfavorable abnormal pKa: substitution of undissociable residue for glutamic acid-35 in chicken lysozyme.

Glu35 in chicken lysozyme has an abnormally high pKa (6.1) partly due to the hydrophobic environment provided by Trp108. The relationship between protein stability and abnormal pKa was investigated in detail by using mutant lysozymes in which Glu35 was replaced by undissociable residues and an oppositely ionizable residue. It was found that lysozyme was stabilized at alkaline pH range by the replacement of Glu35 with an undissociable residue, Gln (E35Q lysozyme) or Al (E35A lysozyme). On the other hand, when Glu35 was replaced by His (E35H lysozyme), which could have an opposite charge to Glu by ionization, the introduced His35 was found to have an abnormally low pKa (3.6), leading to the destabilization of lysozyme at acidic pH. These observations are completely consistent with the situation that the environment around Glu35 is highly hydrophobic and therefore the placement of either a positive or negative charge in such an environment leads to destabilization of lysozyme. These observations also indicate that the replacement of an acidic residue having abnormally high pKa or a basic residue having abnormally low pKa by an undissociable residue is a very efficient and general method for stabilization of a protein.

Animals↗

Binding selectivity of rhizoxin, phomopsin A, vinblastine, and ansamitocin P-3 to fungal tubulins: differential interactions of these antimitotic agents with brain and fungal tubulins.

The binding of four potent antimitotic agents, rhizoxin (RZX), phomopsin A (PMS-A), ansamitocin P-3 (ASMP-3), and vinblastine (VLB), to tubulins from RZX-sensitive and -resistant strains of Aspergillus nidulans, Schizosaccharomyces pombe, and Saccharomyces cerevisiae was investigated. Mycelial extracts to which RZX could bind contained beta-tubulin with Asn as the 100th amino acid residue (Asn-100) in all cases, and those without affinity for RZX contained beta-tubulins with either Ile-100 or Val-100. Though PMS-A shares the same binding site as RZX and ASMP-3 on porcine brain tubulin (Asn-100), only ASMP-3 bound Asn-100 fungal tubulins in a competitive manner with respect to RZX. PMS-A and VLB, which strongly bind to porcine brain tubulin, did not bind to any of the fungal mycelial extracts examined. The results indicate differential interactions of these antimitotic agents with brain and fungal tubulins.

Animals↗

Two thrombin-activated Ca2+ channels in human platelets.

The regulation of extracellular Ca2+ entry into fura-2-loaded human platelets was examined following stimulation with thrombin. In the presence of external Ca2+, stimulation of platelets with thrombin resulted in a rapid increase, followed by a plateau, in intracellular Ca2+ concentration ([Ca2+]i). Pretreatment with wortmannin, a specific inhibitor of myosin light chain kinase, suppressed only the plateau phase and had no effect on the initial rapid increase in [Ca2+]i. In Ca(2+)-free EGTA buffer, thrombin induced a transient and relatively small increase in [Ca2+]i caused by Ca2+ release from internal stores. When Ca2+ was added subsequently to the Ca(2+)-free medium within 10 min after thrombin activation, a marked increase in [Ca2+]i was seen, reflecting thrombin-stimulated external Ca2+ entry. With the Ca(2+)-free medium, wortmannin did not affect either the Ca2+ mobilization from the internal stores or the rapid external Ca2+ entry at early time points (within 5 s) after thrombin stimulation, whereas it significantly inhibited Ca2+ entry when Ca2+ was added later (at 3 min). Wortmannin inhibition of this late Ca2+ entry and that of 20-kDa myosin light chain phosphorylation after thrombin stimulation were dose- and preincubation time-dependent and correlated well with each other. These results suggest that two different channels are responsible for Ca2+ entry in human platelets at the early and late phases of thrombin stimulation and that the channel responsible for the late phase of Ca2+ entry may be activated by a mechanism involving myosin light chain kinase.

Androstadienes↗

Molecular cloning and expression of rat liver N-heparan sulfate sulfotransferase.

N-Heparan sulfate sulfotransferase catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to the nitrogen of glucosamine in heparan sulfate. The enzyme has been previously purified to apparent homogeneity from rat liver (Brandan, E., and Hirschberg, C. B. (1988) J. Biol. Chem. 263, 2417-2422). We have now cloned the rat liver enzyme using the following strategy: (a) the amino acid sequence was obtained from tryptic peptides of the purified protein, (b) mixed oligonucleotides were generated based on the sequence of the tryptic peptides, (c) a polymerase chain reaction fragment was obtained using mixed oligonucleotide interprimer amplification of cDNA, and (d) this fragment was used to screen rat liver lambda gt 10 and lambda ZAP libraries. Three clones were obtained, one of which seems to contain the complete coding sequence of the N-heparan sulfate sulfotransferase (N-HSST). Evidence that the cDNA clone corresponds to the previously purified and characterized N-HSST was the following: (a) the predicted sequence of the N-HSST contains all of the 11 tryptic peptides obtained from the purified protein, (b) when a cDNA containing the sequence coding for the N-HSST was introduced in a eukaryotic expression vector and transfected in COS-1 cells, the enzyme activity was expressed 9-fold over controls, and (c) the characteristic of the predicted protein fits with the purified protein in terms of molecular weight, membrane localization, and its being an N-linked glycoprotein. The size of the longest cDNA isolated is 4.1 kilobases, which is in close agreement with the 4.2-kilobase size of one of the mRNA observed in Northern analyses. In addition, messages of 7.0 and 8.5 kilobases were also observed, suggesting that a large portion is untranslated. The latter messages were the major mRNA species detected.

Amino Acid Sequence↗

Anticardiolipin antibodies in NZW x BXSB F1 mice. A model of antiphospholipid syndrome.

NZW x BXSB F1 (W/B F1) male mice develop systemic lupus-like disease, and several autoantibodies, circulating immune complexes, and lupus nephritis become apparent. The abnormally high incidence of degenerative coronary vascular disease with myocardial infarction and thrombocytopenia due to the presence of both platelet-associated antibodies and circulating antiplatelet antibodies in this animal has been reported. We found that W/B F1 male mice produced autoantibodies against cardiolipin (aCL) and that the titer of aCL increases with age. aCL from W/B F1 male mice were mainly IgG and binding activity to cardiolipin was aCL-cofactor (beta 2-glycoprotein I (beta 2-GPI)) dependent. We developed monoclonal aCL from these animals and examined specificity of the autoantibodies. All the mAb used reacted with the negatively charged phospholipids, cardiolipin, phosphatidylserine, and phosphatidylinositol, and some reacted with platelets and DNA. The addition of human or mouse beta 2-GPI enhanced the titer for monoclonal aCL from the W/B F1 mice. From the results of competitive inhibition enzyme immunoassay with monoclonal aCL and purified beta 2-GPI, aCL from the W/B F1 mice recognized the complex of CL and beta 2-GPI. The W/B F1 male mouse may be an appropriate model for use in studies on the pathologic significance of aCL in patients with antiphospholipid syndrome.

Animals↗