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Biomedical subjects

H Inaba

Publications and source records attributed to H Inaba.

At least 19 recordsLinked to original sources
PubMed1998

Flow cytometric analysis of peripheral blood and bone marrow for tumor cells in patients with neuroblastoma.

BACKGROUND: Several sensitive surveillance tests reportedly have been used to detect occult neuroblastoma (NB) cells in peripheral blood (PB) and bone marrow (BM). They may be useful in monitoring minimal residual tumor cells. The authors report the feasibility and clinical usefulness of a sensitive flow cytometric assay that has been newly developed and evaluated to detect NB cells. METHODS: Nine NB patients and 15 healthy donors were included in the current study. Primary tumor tissues, BM, and PB were examined for the detection of NB cells using a triple-color flow cytometric assay. Tumor cells in PB and BM, isolated by fluorescence-activated cell sorting, were used for morphologic studies and differential polymerase chain reaction analysis of N-myc gene amplification. RESULTS: Neuroblastoma cells consistently showed CD9+/CD56+/CD45- phenotype. Flow cytometric analysis could detect NB cells at a level of 1 per 10(4-5) cells. The CD9+/CD56+/CD45- cell population was absent in normal PB and BM. This assay identified occult NB cells, which were not detected by conventional cytology, in PB and BM obtained from six patients (one of two with Stage II and all five with advanced disease) at diagnosis. Residual NB cells also were detected in PB and BM during therapy. Neuroblast-like morphology and N-myc gene amplification of sorted cells confirmed that CD9+/CD56+/CD45- cells were truly NB cells. CONCLUSIONS: A triple-color flow cytometric assay was a sensitive and specific method to detect occult NB cells in PB and BM. This assay could be an additional component of surveillance testing for NB patients.

Antigens, CD↗
PubMed1998

Hydrogen peroxide derived from hepatocytes induces sinusoidal endothelial cell apoptosis in perfused hypoxic rat liver.

BACKGROUND & AIMS: Evidence is accumulating that hypoxic liver injury involves not only necrosis but also apoptosis. Reactive oxygen species can cause apoptosis. This study examined the hypothesis that H2O2 induces apoptosis in hypoxic rat liver. METHODS: Blood-perfused rat livers were made hypoxic by reducing the perfusion flow. H2O2 was detected by both 2',7'-dichlorofluorescein fluoroimaging and cerium electron-microscopic methods. To evaluate the apoptosis, the liver was stained with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method. To further investigate the involvement of H2O2 in hypoxia-induced liver cell apoptosis, small pieces of liver in the cultured media were exposed to 0.5 mmol/L of reagent H2O2 and stained with the TUNEL method. RESULTS: In the hypoxic liver, H2O2 was produced predominantly by hepatocytes, and the number of apoptotic nonparenchymal cells was significantly increased, particularly in the midzone. All the apoptotic cells were positively stained with monoclonal antibody against the hepatic sinusoidal endothelial cells (SECs). In incubated liver pieces, reagent H2O2 induced apoptosis selectively in SECs. CONCLUSIONS: Low-flow hypoxia induces H2O2 production in hepatocytes, and this H2O2 induces apoptosis selectively in SECs in the rat liver.

Animals↗
PubMed1997

Thoracoscopic cardiomyoplasty: a canine feasibility study.

BACKGROUND: Thoracoscopy may be effective in reducing the surgical stress of cardiomyoplasty. The feasibility of thoracoscopy in cardiomyoplasty was investigated. METHODS: Cardiomyoplasty by thoracoscopy and by the open method through a thoracotomy was performed in dogs. After 8 to 10 weeks of preconditioning, the hemodynamic effect of burst stimulation was measured. RESULTS: Cardiomyoplasty by thoracoscopy took 90 +/- 21 minutes (mean +/- standard deviation), whereas cardiomyoplasty by the open method took 67 +/- 10 minutes (p < 0.05). As a result of burst stimulation, aortic pressure, descending aortic flow, and left atrial pressure increased by 15.1% +/- 6.5%, 8.6% +/- 6.3%, and 3.8% +/- 4.6%, respectively, in the dogs that received the cardiomyoplasty by thoracoscopy, whereas those indices increased by 16.5% +/- 6.9%, 9.8% +/- 5.9%, and 4.8% +/- 4.2%, respectively, in dogs that received cardiomyoplasty by the open method. No significant difference between the two groups was shown in any index. CONCLUSIONS: Cardiomyoplasty by thoracoscopy was technically practical, and its hemodynamic effect was similar to that of the open method. The feasibility of cardiomyoplasty by thoracoscopy was thereby suggested.

Animals↗
PubMed1997

mRNA expression of Fas receptor (CD95)-associated proteins (Fas-associated phosphatase-1/FAP-1, Fas-associating protein with death domain/FADD, and receptor-interacting protein/RIP) in human leukaemia/lymphoma cell lines.

mRNA expression of Fas (CD95)-associated proteins [Fas-associating protein with death domain (FADD), receptor-interacting protein (RIP), and Fas-associated phosphatase-1 (FAP-1)] has been investigated in 26 Fas-positive human leukaemia/lymphoma cell lines. Reverse transcriptase-polymerase chain reaction analysis revealed that FADD and RIP mRNA were invariably expressed in both Fas-sensitive and Fas-insensitive cell lines. However, FAP-1 mRNA was detected in only 11 of 26 cell lines. Interestingly 7/14 cell lines in the Fas-sensitive group were positive for FAP-1 mRNA expression. 8/12 cell lines in the Fas-refractory group did not express FAP-1 mRNA, but half of these cell lines were susceptible to tumour necrosis factor alpha-induced growth inhibition. These findings suggest that the presence or absence of FAP-1 mRNA expression did not always correlate with relative sensitivity of Fas-mediated growth inhibition. Furthermore, it is assumed that leukaemia/lymphoma cells could possess structural or functional defects of Fas or Fas-associated proteins resulting in the failure to trigger apoptotic cell death.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Coherent detection techniques in optical imaging of tissues.

To form optical images from the transmitted or reflected light that is multiply scattered inside biological tissue, several detection techniques that extract the least-scattered photons or path-resolved photons have been developed. This paper reviews the coherent detection techniques. Emphasis is put on coherent detection imaging methods based on optical heterodyning, whose attractive features include quantum-noise-limited sensitivity, wide dynamic range, and excellent directionality and selectivity. Coherent detection methods have been implemented to achieve laser computed tomography and micrometre-resolution cross-sectional images in both in vivo and in vitro biological systems. Imaging works by ourselves and others are described, and an experimental study on coherent photon migration through highly scattering media is described to aid the understanding of the coherent detection method in selectively detecting the signal-carrying photons.

Diagnostic Imaging↗
PubMed1997

Isoflurane attenuates early neutrophil-independent hypoxia-reoxygenation injuries in the reperfused liver in fasted rats.

BACKGROUND: Ischemia-hypoxia followed by reperfusion and reoxygenation injures cells and organs. Previous studies have indicated that isoflurane may protect organs from ischemia-reperfusion or hypoxia-reoxygenation. This study investigated the ability of isoflurane to protect the liver from hypoxia-reoxygenation injury and the mechanisms of this phenomenon. METHODS: The isolated liver was perfused at a constant pressure of 12 cm H2O with a modified Krebs-Ringer-bicarbonate solution saturated with a 95% oxygen/5% carbon dioxide gas mixture. Hypoxic perfusion produced by decreasing the oxygen concentration in the gas mixture to 10% was followed by perfusion at 95% oxygen for 60 min. Viability of the liver was assessed by lactate dehydrogenase release from the liver. Isoflurane at 0.5, 1, and 2 minimum alveolar concentration was administered to assess the effect of isoflurane on hypoxia-reperfusion injury. To determine the effect of isoflurane on extracellular generation of superoxide in the liver, the reduction of ferricytochrome c with or without superoxide dismutase was measured. RESULTS: Lactate dehydrogenase release was transiently but dramatically increased by reoxygenation and significantly attenuated by 1 and 2 minimum alveolar concentration of isoflurane. Suppression of Kupffer cells with gadolinium chloride also attenuated the lactate dehydrogenase release. Isoflurane significantly reduced the superoxide generation on reperfusion. CONCLUSIONS: The results show that isoflurane protected the liver from an early reoxygenation injury presumably mediated by Kupffer cells. The mechanisms of the inhibitory effects of isoflurane on the injury may involve suppression of extracellular superoxide generation during reoxygenation.

Anesthetics, Inhalation↗
PubMed1997

Variant of intron 22 inversions in the factor VIII gene in severe hemophilia A.

Recurrent DNA inversions, which disrupt the factor VIII (FVIII) gene, generally occur between a region of intron 22 (int22h) and one of two homologous copies of this region, located 300 to 400 kb telomeric to the FVIII gene. This report describes a patient with severe hemophilia A and a high level inhibitor with atypical hybridization patterns. A Bcl I Southern blot assay was altered to 17.5, 16, and 14 kb. His mother and two out of four aunts tested had normal and abnormal restriction patterns which led to a total of five different fragments, suggesting that they were carriers. The Xba I plus Kpn I restriction fragment-length polymorphism in intron 22 by Southern blotting using the same probe (probe a) yielded the 6.2 kb polymorphic band, with a clearly separated 6.6 kb band from the non-factor VIII region; an alternative int22h hybridization probe (probe x) detected no additional fragment. These results suggest that probe a as well as probe x could recognize an intron-22-sized fragment. This report shows a variation in the number of int22h copies although we could not find the inversion junction.

Adult↗
PubMed1997

Heat shock protein 70 messenger RNA reflects the severity of ischemia/hypoxia-reperfusion injury in the perfused rat liver.

OBJECTIVES: To determine whether ischemia-reperfusion and hypoxia-reoxygenation cause cellular damages and stress responses in an isolated perfused rat liver model. To determine whether the increased synthesis of stress protein messenger RNA reflects cellular injury. DESIGN: Prospective, controlled study. SETTING: Institutional laboratories. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Isolated rat livers with cell free perfusion were exposed to various periods of ischemia-reperfusion or hypoxia-reoxygenation. MEASUREMENTS AND MAIN RESULTS: We measured hepatic oxygen consumption and alanine aminotransferase leakage from liver during perfusion. We analyzed the gene expression of heat shock protein 70, a major stress protein, of the liver by Northern blotting after perfusion. The expression of heat shock protein 70 messenger RNA augmented as the reperfusion period increased. The expression level after graded ischemia or hypoxia significantly correlated with the calculated hepatic oxygen debt (r2 = .737; p < .001; n = 21), or with the accumulated alanine aminotransferase leakage from the liver (r2 = .509; p < .001; n = 21). CONCLUSIONS: These results suggest that the accumulation of heat shock protein 70 messenger RNA reflects the severity of ischemia-reperfusion and hypoxia-reoxygenation injuries, and that a stress response in reperfusion can be triggered without formed elements of blood.

Alanine Transaminase↗
PubMed1997

Effects of volatile anesthetics on the calcium ionophore A23187-mediated alterations in hepatic flow and metabolism in the perfused liver in fasted rats.

Alterations in intracellular calcium homeostasis have been implicated in heptic injury. Volatile anesthetics modulate the homeostasis of intracellular calcium. The effects of volatile anesthetics on the hemodynamic and metabolic alterations induced by the calcium ionophore A23187 were studied using isolated liver perfusion in fasted rats. The liver was isolated from 24 hr-fasted male Sprague-Dawley rats, and perfused through the portal vein at a constant pressure of 1.2 kPa in a recirculating perfusion-aeration system. Halothane, isoflurane and sevoflurane were administered at 2%, 3% and 4.4%, respectively. All volatile anesthetics maintained basal hepatic flow, reduced oxygen consumption, and transiently enhanced net lactate production. A23187 at initial concentrations of 0.8 to 3.2 microM decreased hepatic flow and oxygen consumption in a dose-dependent manner, and enhanced lactate production. All anesthetics significantly attenuated the decreases in hepatic flow and oxygen consumption after administration of A23187 at 1.6 microM. None of the anesthetics significantly influenced the A23187-induced enhancement of net lactate production. Volatile anesthetics may attenuate the hepatic vasoconstriction and oxygen debt induced by intracellular calcium overload.

Anesthetics, Inhalation↗
PubMed1997

Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene.

Although the molecular defect in patients in a Japanese family with mild to moderately severe hemophilia A was a deletion of a single nucleotide T within an A8TA2 sequence of exon 14 of the factor VIII gene, the severity of the clinical phenotype did not correspond to that expected of a frameshift mutation. A small amount of functional factor VIII protein was detected in the patient's plasma. Analysis of DNA and RNA molecules from normal and affected individuals and in vitro transcription/translation suggested a partial correction of the molecular defect, because of the following: (i) DNA replication/RNA transcription errors resulting in restoration of the reading frame and/or (ii) "ribosomal frameshifting" resulting in the production of normal factor VIII polypeptide and, thus, in a milder than expected hemophilia A. All of these mechanisms probably were promoted by the longer run of adenines, A10 instead of A8TA2, after the delT. Errors in the complex steps of gene expression therefore may partially correct a severe frameshift defect and ameliorate an expected severe phenotype.

DNA Replication↗
PubMed1997

[An operative case of bilateral peripheral pulmonary arterial aneurysms].

An operative case of bilateral peripheral pulmonary arterial aneurysms is described. Nine cases of bilateral peripheral pulmonary arterial aneurysms reported in Japan are reviewed. The patient was a 26-year-old woman complaining of massive hemoptysis. Her chest X-ray showed coin lesions in the bilateral hilus region. After admission, body CT and pulmonary arteriography revealed saccular dilatation of the bilateral peripheral pulmonary artery. We diagnosed as bilateral peripheral pulmonary arterial aneurysms. Bronchoscopic examination revealed bleeding from the left lower lobe bronchus. She underwent left lower lobectomy. Histological examination of the resected specimen demonstrated a marked destruction of the wall of the aneurysm. This patient died of recurrence of hemoptysis from bilateral lung on the 42nd postoperative day.

Adult↗
PubMed1997

[A case of successful treatment with ganciclovir for cytomegalovirus pneumonia after pulmonary lobectomy].

The premortem diagnosis of cytomegalovirus (CMV) pneumonia is usually difficult, and mortality of it is high. A case of successful treatment with ganciclovir for cytomegalovirus pneumonia after pulmonary lobectomy is reported. The patient was a 76-year-old man. Under diagnosis as lung cancer, the right lower lobectomy was performed. After operation, pneumonia occurred on the nonoperated side and in a few days reticular shadows rapidly spread to the whole lung. Although pulse steroid therapy was performed, the interstitial pneumonitis improved only a little. Then intranuclear inclusion body-bearing giant cells were found in sputum obtained by bronchoscopy. So we diagnosed the interstitial pneumonitis as CMV pneumonia and ganciclovir was administrated. CMV pneumonia had improved for two weeks and the patient has no recurrence. When interstitial pneumonitis develop in patients after operation or steroid therapy, the differential diagnosis should include the possibility of CMV pneumonia.

Aged↗
PubMed1996

Design of a suitable formulation of FK613, a novel antiallergic agent, based on its pharmacokinetic and pharmacodynamic properties in healthy subjects.

The pharmacokinetic and pharmacodynamic properties of FK613, a novel indolyl piperidine derivative, were investigated after oral administrations of 5, 10 and 20 mg in hard gelatin capsules to healthy male volunteers. FK613 was rapidly and almost completely absorbed, and >89% was recovered in the urine as the unchanged form. The urinary excretion of FK613 was linearly correlated with plasma concentration and its low water solubility was the main concern regarding the safety. In another experiment using a double-blind crossover design, in which 0 (placebo), 5 and 20 mg FK613 were administered to determine the plasma concentration-effect relationship, suppression of the intradermal histamine-induced skin reaction by FK613 was observed. Thus, the maintenance of a plasma concentration of FK613 in the range of 80-250 ng center dot ml-1 was recommended to ensure the suppression of histamine-induced wheal by >50% and not to exceed the solubility in urine. To achieve this, a new hydrogel-type formulation of FK613 was developed, with the aim both of delaying its absorption, so as to suppress the sharp rise in plasma concentration, and of maintaining the effective concentration for a longer period of time. This formulation was administered after meals at the doses of 20, 30, 40, 50 and 60 mg, and at repeated doses of 40 mg twice daily for 6.5 days to evaluate the pharmacokinetics and safety in healthy subjects. The area under the plasma concentration curve increased linearly with dose, whereas maximum plasma concentration (Cmax) tended to peak as dose increased, indicating the desirable properties of this formulation. Although Cmax exceeded 250 ng/ml at doses of 30 mg or more, no urinary crystal formation was observed on careful inspection of urine.

Adult↗
PubMed1996

High-dose fentanyl does not suppress interleukin-1 beta-induced increases in plasma ACTH and corticosterone in rats.

BACKGROUND: High-dose fentanyl anesthesia is reported to attenuate the metabolic and endocrinal responses to surgery. Interleukin-1 (IL-1) is one of the key mediators in the immunoneuroendocrine system, and may be involved in the stress responses to surgery. We studied whether high-dose fentanyl may influence the IL-1 beta-induced alterations in plasma ACTH and corticosterone in rats. METHODS: Plasma ACTH, corticosterone, blood pressure, heart rate and acid-base status were determined in either awake or fentanyl-anesthetized animals immediately before and after either phosphate buffered saline or IL-1 beta administration. Fentanyl anesthesia was induced by bolus intravenous injections of fentanyl at 50 micrograms/kg and pancuronium bromide at 0.2 mg/kg, and maintained by continuous administrations of fentanyl at 100 or 200 micrograms.kg-1.h-1 and pancuronium bromide at 0.4 microgram.kg-1.h-1. RESULTS: In awake rats, IL-1 beta at incremental doses of 0.25, 0.5 and 1 microgram/kg increased plasma ACTH in a dose-dependent manner, but heat-inactivated IL-1 beta at 4 micrograms/kg did not influence plasma ACTH. A noxious stimulus with tail clamping for 30 min did not significantly alter plasma ACTH in fentanyl-anesthetized rats. Fentanyl reduced the basal plasma corticosterone, but it did not modulate the increases in plasma ACTH and corticosterone after the administration of IL-1 beta at 1 microgram/kg. Fentanyl moderately increased the basal blood pressure and heart rate, but it moderately attenuated the IL-1 beta-induced elevations of blood pressure and heart rate. IL-1 beta moderately decreased PCO2 in awake animals. CONCLUSIONS: Fentanyl anesthesia, which is able to suppress the endocrine responses to noxious stimuli, does not attenuate the IL-1 beta-mediated activation of the pituitary-adrenal axis in rats.

Adrenocorticotropic Hormone↗
PubMed1996

Effects of halothane, isoflurane and sevoflurane on ischemia-reperfusion injury in the perfused liver of fasted rats.

BACKGROUND: Although intraoperative ischemia-reperfusion of the liver generally occurs under general anesthesia, little is known about the direct effect of anesthetic agents on hepatic injury due to this phenomenon. The effect of volatile anesthetics on ischemia-reperfusion injury was studied using isolated liver perfusion. METHODS: The liver was isolated from 24-h-fasted male Sprague-Dawley rats and perfused through the portal vein with a modified Krebs-Ringer bicarbonate solution in a recirculating perfusion-aeration system. Ischemia was induced by reducing the baseline perfusion pressure from 1.2 to 0.2 kPa followed by reperfusion to baseline level. The ischemia-reperfusion injury was assessed by LDH release from the perfused liver. We studied the effect of halothane, isoflurane and sevoflurane on the ischemia-reperfusion injury during 20 min of control conditions, exposure of the liver to 60 min of ischemia and reperfusion for 90 min. RESULTS: Ischemia was evident by reduced portal vein flow and oxygen consumption, and caused an increase in lactate production. Reperfusion caused a transient reduction in lactate production and a significant increase in LDH release. All anesthetics reduced hepatic oxygen consumption and increased the net lactate production during control conditions. Volatile anesthetics also significantly attenuated LDH release during reperfusion. The suppression of LDH release was observed even when isoflurane was administered during the reperfusion period, but not when it was administered only during ischemia. CONCLUSION: These results indicate that volatile anesthetics may protect the fasted liver from early, neutrophil-independent, ischemia-reperfusion injury by acting during the reperfusion phase.

Anesthetics, Inhalation↗