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Biomedical subjects

R Shimizu

Publications and source records attributed to R Shimizu.

At least 37 records · Page 2Linked to original sources
PubMed2000

GATA factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant deficiencies.

GATA-1 germline mutation in mice results in embryonic lethality due to defective erythroid cell maturation, and thus other hematopoietic GATA factors do not compensate for the loss of GATA-1. To determine whether the obligate presence of GATA-1 in erythroid cells is due to its distinct biochemical properties or spatiotemporal patterning, we attempted to rescue GATA-1 mutant mice with hematopoietic GATA factor complementary DNAs (cDNAs) placed under the transcriptional control of the GATA-1 gene. We found that transgenic expression of a GATA-1 cDNA fully abrogated the GATA-1-deficient phenotype. Surprisingly, GATA-2 and GATA-3 factors expressed from the same regulatory cassette also rescued the embryonic lethal phenotype of the GATA-1 mutation. However, adult mice rescued with the latter transgenes developed anemia, while GATA-1 transgenic mice did not. These results demonstrate that the transcriptional control dictating proper GATA-1 accumulation is the most critical determinant of GATA-1 activity during erythropoiesis. The results also show that there are biochemical distinctions among the hematopoietic GATA proteins and that during adult hematopoiesis the hematopoietic GATA factors are not functionally equivalent.

Animals↗
PubMed2000

Structures of TMC-95A-D: novel proteasome inhibitors from Apiospora montagnei sacc. TC 1093.

Four novel proteasome inhibitors, TMC-95A-D (1-4) have been isolated from the fermentation broth of Apiospora montagnei Sacc. TC 1093, isolated from a soil sample. All of the molecular formulas of 1-4 were established as C(33)H(38)N(6)O(10) by high-resolution FAB-MS. Their planar structures were determined on the basis of extensive analyses of 1D and 2D NMR, and degradation studies. Compounds 1-4 have the same planar structures to each other, and are unique highly modified cyclic peptides containing L-tyrosine, L-aspargine, highly oxidized L-tryptophan, (Z)-1-propenylamine, and 3-methyl-2-oxopentanoic acid units. The absolute configuration at C-11 and C-36 of 1-4 was determined based on chiral TLC and HPLC analyses of their chemical degradation products. The ROESY analysis along with (1)H-(1)H coupling constants clarified the absolute stereochemistry at C-6, -7, -8, and -14 of the cyclic moieties. These studies revealed the relationships of 1-4 to be diastereomers at C-7 and C-36.

Cysteine Endopeptidases↗
PubMed2000

Novel molecular defects of the delta-aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria.

Cloning and expression of the defective gene for delta-aminolevulinate dehydratase (ALAD) from the second of 2 German patients with ALAD deficiency porphyria (ADP), who had been originally reported by Doss et al. in 1979, were performed. Cloning of cDNAs for the defective ALAD were performed using Epstein-Barr virus (EBV)-transformed lymphoblastoid cells of the proband, and nucleotide sequences of cloned cDNA were determined. Two separate mutations of ALAD cDNA were identified in each ALAD allele. One was G457A, termed "H1," resulting in V153M substitution, while the other was a deletion of 2 sequential bases at T(818) and C(819), termed "H2," resulting in a frame shift with a premature stop codon at the amino acid position of 294. Using allele-specific oligonucleotide hybridization, the mother of the proband was shown to have an H1 defect, while using genomic DNA analysis, the father was shown to have an H2 defect. Expression of H1 cDNA in Chinese hamster ovary cells produced an ALAD protein with only a partial activity (10.65% +/- 1.80% of the normal), while H2 cDNA encoded no significant protein. These data thus demonstrate that the proband was associated with 2 novel molecular defects of the ALAD gene, 1 in each allele, and account for the extremely low ALAD activity in his erythrocytes ( approximately 1% of normal).

Acute Disease↗
PubMed2000

Comparison of the effects of amrinone, milrinone and olprinone in reversing bupivacaine-induced cardiovascular depression.

BACKGROUND: Increasing evidence indicates that amrinone, a phosphodiesterase fraction III (PDE-III) inhibitor, has relative efficacy as an initial treatment for cardiovascular depression after bupivacaine in an experimental setting. This study was performed to compare the cardiovascular effects of the other new PDE-III inhibitors, milrinone and olprinone, with those of amrinone in reversing bupivacaine-induced cardiovascular depression. METHODS: In sevoflurane-anaesthetized dogs, bupivacaine was infused intravenously at 1 mg x kg(-1) x min(-1) until mean arterial pressure fell to 60 mmHg or less. The dogs received either amrinone (2 mg x kg(-1)), milrinone (0.2 mg x kg(-1)), olprinone (0.12 mg x kg(-1)) or 0.9% saline (0.5 ml x kg(-1)). RESULTS: Amrinone, milrinone and olprinone improved left ventricular systolic and diastolic function, resulting in an increase in cardiac index. The most significant difference observed among the three drugs was the change in heart rate (HR) after treatment. Milrinone significantly increased HR, but olprinone did not. CONCLUSION: Milrinone and olprinone are as effective as amrinone in reversing bupivacaine-induced cardiovascular depression.

Amrinone↗
PubMed2000

The fiberscopic findings of the epidural space in pregnant women.

BACKGROUND: The spread of epidural analgesia is facilitated by pregnancy. Changes in the epidural structure during pregnancy may affect the spread of analgesia in pregnant women. To investigate the changes in the epidural space produced by pregnancy, the authors performed epiduroscopy in pregnant women. METHODS: Using a flexible fiberscope, the authors evaluated the epidural space in 73 women undergoing lumbar epidural anesthesia. Patients were classified into three groups: a nonpregnant group (n = 21), a first trimester pregnant group (8-13 weeks, n = 23), and a third-trimester pregnant group (27-39 weeks, n = 29). A 17-gauge Tuohy needle was inserted using the paramedian technique and the loss-of-resistance method with 5 ml air. The epiduroscope was introduced into the lumbar epidural space via the Tuohy needle and was advanced approximately 10 cm in a cephalad direction from the needle tip within the epidural space. The differences in the epidural space among the three groups then was evaluated. RESULTS: The epiduroscopy showed that the epidural pneumatic space, after injection of a given amount of air, was narrower and the density of the vascular network greater in the third-trimester group than in the other two groups. The amount of engorged blood vessels was greater in the third and first trimester groups than in the nonpregnant group. The amount of bleeding at the needle tip and the amount of fatty and fibrous connective tissue did not differ among the three groups. CONCLUSIONS: Epidural blood vessels become engorged in the first trimester; the density of the vascular networks increase in the third trimester. These changes in the epidural space during pregnancy may affect the spread of epidural analgesia in pregnant women.

Adult↗
PubMed2000

Pharmacokinetic/pharmacodynamic relationship of eptazocine, a narcotic-antagonist analgesic, in rats.

The relationship between the pharmacokinetics and the pharmacodynamics of eptazocine, a narcotic-antagonist analgesic, was investigated in rats. The analgesic effect of eptazocine (2.5, 5 and 10 mg/kg) following intravenous (i.v) administration was evaluated by both the Randall-Selitto method and the D'Amour-Smith method. The analgesic effects were determined before and at designed intervals for a period of 120 min after eptazocine administration, and are expressed as area under the effect-time curve (AUC(E)). The plasma concentration of eptazocine was determined by fluorescence HPLC and was analyzed with a two compartment open model using the nonlinear least-squares method. Eptazocine produced a dose-dependent analgesic effect. It was demonstrated that eptazocine has a linear relationship between AUC(E) and the area under the plasma concentration-time curve (AUC) following i.v. administration for three different doses ranging from 2.5 to 10 mg/kg.

Analgesics↗
PubMed2000

[Low-dose prednisolone therapy for idiopathic thrombocytopenic purpura].

Prednisolone (PSL) is widely used for the treatment of idiopathic thrombocytopenic purpura (ITP). We compared the effects of a relatively low dose (0.5 mg/kg/day, LD group) of PSL and the conventional dose (1.0 mg/kg/day, CD group) on 59 ITP patients. Twenty-six patients were treated with low-dose PSL, and 23 patients with the conventional dose. No statistically significant difference was observed in the complete remission rates for the LD group (35%) and the CD group (39%). However, the mean duration of hospitalization was significantly (p < 0.001) shorter for LD group patients than for patients in the CD group (20 days versus 50 days, respectively). In conclusion, low-dose PSL may be as effective as the conventional dose and capable of reducing the cost of hospitalization, thus, improving the quality of life for patients with ITP.

Anti-Inflammatory Agents↗
PubMed2000

[Anesthetic management of a patient with May-Hegglin anomaly].

The May-Hegglin anomaly is a rare hereditary disorder characterized by the presence of giant platelets and platelet deficiency. This report presents a successful management of a patient with May-Hegglin anomaly. A 5-year-old girl with May-Hegglin anomaly was scheduled for closure of fistulae of her ears. Although preoperative physical examination revealed platelet count of 8,000 mm-3, she had no bleeding tendency. No premedication was given. Anesthesia was induced with inhalational agents of a mixture of sevoflurane, nitrous oxide and oxygen. Neuromuscular blockade was achieved with vecuronium 0.1 mg.kg-1 and the trachea was gently intubated. Anesthesia was maintained with sevoflurane, nitrous oxide and oxygen. Five units of platelet were transfused during the operation. No bleeding tendency was observed perioperatively. It is important to plan the management of anesthesia for a patient with bleeding tendency.

Anesthesia, Inhalation↗
PubMed2000

[Anesthetic management of concomitant coronary artery bypass grafting without cardiopulmonary bypass and left lower lobectomy].

This case report describes an anesthetic management of a patient who received successful concomitant coronary artery bypass grafting without cardiopulmonary bypass and left lower lobectomy. A 66-year-old man presented for left lower lobectomy. His medical history included angina pectoris under control with isosorbide and nifedipine. Preoperative coronary angiography revealed multiple stenosis [100% at right coronary artery (# 2), 99% at left anterodescending artery (# 7) and 90% at left circumflex artery (# 11)]. Concomitant coronary artery bypass grafting without cardiopulmonary bypass and left lower lobectomy were scheduled. Anesthesia was maintained with combined total intravenous anesthesia (propofol and fentanyl) and continuous thoracic epidural anesthesia. Postoperative pain was well controlled with continuous epidural analgesia (TEA) and patient control analgesia (PCA). There were no signs of postoperative respiratory complications and myocardial ischemia. Combined total intravenous and continuous thoracic epidural anesthesia has multiple benefits for concomitant coronary artery bypass grafting without cardiopulmonary bypass and left lower lobectomy.

Aged↗
PubMed1999

Optical monitoring of the neural activity evoked by mechanical stimulation in the earthworm nervous system with a fluorescent dye, FM1-43.

In the central nervous system of the earthworm, sensory and motor neurons have direct synapses on three giant fibers. To determine the locations of synapses and neural network activated by mechanical stimuli, we optically monitored the activity-dependent staining in the earthworm ventral nerve cord with a styryl dye, N-(3-triethylammoniumpropyl)-4- (4-(dibutylamino)styryl)pyridinium dibromide (FM1-43), and a confocal laser scanning microscope. When scratch stimulus was applied to the body wall of the earthworm, bright fluorescent spots with 3-10 microns in diameter localized only in the stimulated segmental ganglion of the ventral nerve cord. The fluorescent intensity of these spots decreased during dye-free high K+ saline incubation. These results suggest that FM1-43 is useful for activity-dependent staining of invertebrate neurons and their synaptic regions as well as vertebrate nervous system.

Animals↗
PubMed1999

Propofol does not affect the canine cardiac conduction system under autonomic blockade.

PURPOSE: To determine the effects of propofol on the cardiac conduction system in dogs with pharmacological autonomic blockade. METHODS: In eight mongrel dogs receiving 6 mg.kg-1.hr-1 propofol and vecuronium under pharmacological autonomic blockade with atropine and propranolol the infusion rates of propofol were increased from 6, (baseline), to 12, 18 and 24 mg.kg-1.hr-1 at 60-min intervals. An electrophysiological study assessed sinus rate, sinus node recovery time, corrected sinus node recovery time, intraatrial conduction time, AV nodal effective refractory period, Wenckebach cycle length and AV conduction times. Electrocardiographical variables and arterial pressures were also measured. All measurements were repeated at 30 min after the beginning of each infusion of propofol. RESULTS: Propofol did not produce direct effects on the electrophysiological or electrocardiographical variables at any infusion rates. Heart rates did not change at higher infusion rates in the presence of decreases in arterial pressures. CONCLUSION: Propofol did not affect the cardiac conduction system in the presence of autonomic blockade. Thus, the direct cardiac effects of propofol do not play a causative role in the genesis of propofol-associated bradyarrhythmias.

Anesthetics, Intravenous↗
PubMed1999

The epidural structure changes during deep breathing.

PURPOSE: Previous experience has suggested that the insertion of an epidural catheter becomes easier when the patient takes a deep breath. The purpose of this study is to investigate the effects of respiration on the epidural space. METHODS: We examined the epidural space using a flexible epiduroscope in 20 patients undergoing thoracic epidural anesthesia. A 17-gauge Tuohy needle was inserted using the paramedian technique and the loss-of-resistance method with 5 ml air. The epiduroscope was introduced into the epidural space via the Tuohy needle. Each patient was requested to take a deep breath when the epiduroscope was positioned at the needle tip and at approximately 10 cm cephalad from the needle tip within the epidural space. The changes in the epidural structure during deep breathing at each site were then measured. RESULTS: In 80% of the patients, fatty tissue occupied the needle tip. Through the patients' maximal inspiration, the fatty tissue moved and a visible cavity expanded at the needle tip. Cross section area of the visible cavity at the needle tip was greater at the maximal inspiratory level than at the resting expiratory level: 12.1 +/- 6.7% vs 2.8 +/- 2.1% (mean +/- SD, P < 0.0001). In all patients, the visible cavity within the epidural space, which had already been expanded by injected air, became more expanded after maximal inspiration. Cross section area of the visible cavity at the 10 cm cephalad position was greater at the maximal inspiratory level than at the resting expiratory level: 20.6 +/- 10.0% vs 7.0 +/- 5.3% (P < 0.0001). CONCLUSION: Epiduroscopy showed that deep breathing expanded the potential cavity of the epidural space. We suggest that the changes in the epidural structure during deep breathing may assist in the insertion of an epidural catheter.

Adipose Tissue↗
PubMed1999

Dominant negative effect of a truncated erythropoietin receptor (EPOR-T) on erythropoietin-induced erythroid differentiation: possible involvement of EPOR-T in ineffective erythropoiesis of myelodysplastic syndrome.

We isolated a human leukemic cell line UT-7/GM from UT-7, which can differentiate into mature erythroid cells with erythropoietin (EPO) treatment. Using this cell line, we examined the effect of a truncated human EPO receptor (EPOR-T) on EPO-induced erythroid differentiation. Transfection studies revealed that UT-7/GM cells expressing exogenous EPOR-T were likely to undergo apoptosis even in the presence of EPO. In addition, EPOR-T-transfected cells could not differentiate into hemoglobin-positive cells after administration of EPO. These results suggest that EPOR-T is a negative regulator of EPO-induced anti-apoptosis and EPO-induced erythroid differentiation. The EPOR-T form was expressed in seven of nine cases of myelodysplastic syndrome but not in normal controls. In patients with myelodysplastic syndrome, dysregulated expression of EPOR-T may cause apoptosis and blockage of erythroid differentiation, resulting in ineffective erythropoiesis.

Cell Differentiation↗
PubMed1999

An isoenzyme-selective inhibitor of phosphodiesterase 4 and 1, KF19514, may be useful in the treatment of systemic anaphylaxis: an in vivo study in rabbits.

The present study was conducted to determine whether an inhibitor of phosphodiesterases 4 and 1, KF19514, is useful in the treatment of systemic anaphylaxis in fentanyl-anesthetized rabbits. Eighty-two rabbits were randomly allocated to 7 groups. Groups I-1 (0.01 mg x kg(-1)), I-2 (0.1 mg x kg(-1)), and I-3 (1 mg x kg(-1)) received KF19514 10 minutes before antigen challenge, with Group II serving as control. Group IV and Group V received KF19514 and aminophylline 1 minutes after antigen challenge, respectively, with Group III serving as control. The survival rate was higher in Groups I than in Group II, rates were similar in Groups I-1, I-2, and I-3. The survival rate was also higher in Group IV than in Group III. Pulmonary resistance (R(L)) was significantly lower in Groups I-2 and I-3 than in Group II. Dynamic pulmonary compliance (C(dyn)) was significantly higher in Group I-3 than in Group II. Heart rate and central venous pressure were similar in Groups I and II. In Groups III, IV, and V, heart rate and mean arterial pressure were comparable, but central venous pressure in Group IV was significantly lower than in Group V. In conclusion, the administration of KF19514, an inhibitor of PDEs 4 and 1, to rabbits either before or after antigen challenge improved bronchoconstriction provoked by systemic anaphylaxis with minimal concomitant cardiovascular side effects compared with aminophylline, suggesting that this agent may be useful in the treatment of systemic anaphylaxis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

[Severe lightning limb pain induced by spinal anesthesia].

We report a case in which spinal anesthesia induced a severe lightning limb pain. A 71-year-old man presented for prostate biopsy. Preanesthetic examinations revealed slight hypesthesia in the L 5-S 1 dermatomal segments in the right leg. The patient reported that he had received "local anesthetic" in the lumbar spine 16 years previously because of severe lumbago, and that his hyposthesia had originated from the "local anesthetic". Unfortunately we had no way to know the anesthetic technique performed 16 years ago. The spinal anesthesia was uneventfully introduced with a 25 G Quincke needle at the L 3-4 interspace using 2.0 ml 0.3% hyperbaric dibucaine in the left lateral positions. As soon as the patient was put into the supine position, he started to complain about severe lightning pain in the region of his hyposthesic segments. Severe lightning pain completely diminished 4 hours later when the effect of spinal anesthesia disappeared.

Aged↗
PubMed1999

[Anesthetic management for emergency cesarean section in a patient with intracranial hemorrhage due to ruptured arteriovenous malformation].

A 30 year-old pregnant woman (36 weeks) had intracranial hemorrhage due to arteriovenous malformation in the left frontal lobe. She underwent an emergency cesarean section under general anesthesia. To avoid hemodynamic changes and increasing intracranial pressure, intravenous lidocaine and inhaled sevoflurane were given prior to tracheal intubation, and a bolus dose of nicardipine was given prior to tracheal extubation. Emergence from anesthesia was uneventful, and no exacerbation of neurological signs and symptoms were recognized. It is important to control hemodynamic changes during anesthesia for a patient with intracranial hemorrhage due to ruptured arteriovenous malformation.

Adult↗