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Biomedical subjects

K Fujii

Publications and source records attributed to K Fujii.

At least 595 records · Page 33Linked to original sources

Enzyme inhibition by analgesic and hypnotic agents on anaerobic dehalogenation of halothane.

Enzyme inhibition on anaerobic dehalogenation of halothane by various analgesic or hypnotic agents was investigated in vitro using rat liver microsomal fraction. The production rate of chloro-difluoro-ethylene (CDE) and chloro-trifluoro-ethane (CTE), anaerobic metabolites of halothane, was measured when various concentrations of analgesic or hypnotic agents (fentanyl, morphine, pentazocine, buprenorphine, ketamine, diazepam, chlorpromazine and hydroxyzine) were supplemented. Inhibitor constant (Ki) of each agent was calculated and compared with each other. The activity of NADPH-cytochrome c reductase (fp(2)) and NADH-ferricyanide reductase (fp(1)) was measured when each agent was added. The values of inhibitor constants (Ki) for CDE and CTE formation were in the following order from large to small values; morphine (656 microM and 2570 microM), chlorpromazine (49.7 microM and 68.1 microM), ketamine (24.9 microM and 64.4 microM), fentanyl (23.9 microM and 34.6 microM), hydroxyzine (19.2 microM and 50.8 microM), diazepam (17.0 microM and 13.9 microM), buprenorphine (11.2 microM and 22.4 microM), and pentazocine (1.96 microM and 6.67 microM) respectively. Pentazocine inhibited the formation of CDE 300 fold greater than morphine. The activity of fp(2) and fp(1) did not change by the addition of these analgesic or hypnotic agents. These results indicate that various analgesic or hypnotic agents, which are commonly used with halothane in clinical anesthesia, suppress the anaerobic dehalogenation of halothane in vitro. They also imply that the suppression of production of halothane metabolites is the result of direct enzyme inhibition on cytochrome P-450, since these agents did not affect the activity of fp(2) and fp(1) which are flavoproteins existing in the microsomal electron transport system.

Journal Article↗

Tracheoesophageal anastomosis for intractable aspiration pneumonia.

Permanent tracheostomy and tracheoesophageal anastomosis were performed as a means of surgical intervention for the treatment of intractable aspiration pneumonia. Conventional methods of tracheoesophageal anastomosis have entailed various problems. The improved method devised by us uses the special histological features and enables safe and reliable anastomosis. By this method, the tracheal perichondrium is retained and the strength of the anastomosed portion of the trachea is maintained, the failure of sutures due to tension on the anastomotic site being prevented. Also, reanastomosis can be performed after the cure of primary disease.

Aged↗

Management of syringomyelia associated with Chiari malformation: comparative study of syrinx size and symptoms by magnetic resonance imaging.

The authors reviewed the postoperative alteration of symptoms and syrinx size by magnetic resonance imaging (MRI) in 14 consecutive patients with syringomyelia associated with Chiari malformation. The patients were treated according to our treatment regimen and were divided into five groups according to operative modalities: (1) only foramen magnum decompression (D) for small syrinx; (2) D with ventriculoperitoneal (VP) shunt for small syrinx with hydrocephalus; (3) D with syringosubarachnoid (SS) shunt or (4) D with syringoperitoneal (SP) shunt for large syrinx; and (5) only VP shunt for syrinx with hydrocephalus and atlantoaxial dislocation, respectively. From the preoperative and postoperative sagittal MR images, the areas of the spinal cord and syrinx were measured by a digitizer and the syringo-cord (S-C) ratio was calculated. Out of 14 patients, 12 showed a reduction of syrinx size and a stabilization or improvement of symptoms after surgery. In the other two patients, the syrinx size did not change and their symptoms worsened. Magnetic resonance imaging follow-up showed that foramen magnum decompression without shunt is effective for patients with a small syrinx below 35% of the S-C ratio, and foramen magnum decompression with shunt was effective for patients with a large syrinx over 35% of the S-C ratio, but there was no significant difference between the SS and SP shunt group.

Adolescent↗

Survival period of tumor-bearing mice is prolonged after the interferon-gamma-producing gene transfer.

A highly tumorigenic keratinocyte-derived carcinoma cell line, designated as Pam-T, was established from a Pam212 line. The intradermal injection of more than 10(5) of these cells into syngeneic BALB/c mice induced substantial tumors. The tumors progressively enlarged and then invaded the peritoneal cavity leading to the death of the host mice. To comprehensively investigate the effects of interferon-gamma on tumorigenicity, we manufactured interferon-gamma-producing PamT cells by interferon-gamma gene transfer and examined the characteristics of the tumors induced by these cells in syngeneic mice. Interferon-gamma producing cells exhibited an apparently similar in vitro cell growth pattern and in vivo tumor formation to control cells, but the mean survival of the mice with the interferon-gamma-producing cells was significantly longer compared with control mice.

Animals↗

Evaluation of EC-IC bypass for patients with atherosclerotic occlusive cerebrovascular disease: clinical and positron emission tomographic studies.

The authors report clinical evaluations of extracranial-intracranial (EC-IC) bypass surgery for patients presenting with misery perfusion on positron emission tomography (PET) due to atherosclerotic occlusive cerebrovascular disease. Seven patients underwent PET both before and after undergoing EC-IC bypass surgery. Three of the 7 patients had transient ischaemic attacks (TIAs) and 4 had minor strokes. Five of the 7 had unilateral superficial temporal-middle cerebral artery (STA-MCA) anastomosis, one had bilateral STA-MCA anastomoses and one had STA-MCA anastomosis on one side and carotid endarterectomy on the other side. PET showed postoperative improvement in regional cerebral blood flow and metabolism in 5 of the 7 patients. In the remaining 2 patients, one showed no remarkable changes on PET and the other showed exacerbation on PET due to postoperative cerebral infarction. All three patients who had TIAs had no further TIAs after surgery. Two of the 3 patients postoperatively showed improvement in misery perfusion on PET. In the 4 patients who had minor strokes, 2 showed clinical improvements. One of the 2 showed improvement not only in motor function but also in the higher cortical functions such as verbal and performance intelligence quotients. Changes on PET correlated to the clinical improvement in 4 of 7 patients. The EC-IC bypass is therefore effective in patients with haemodynamic hypoperfusion syndromes by improving the state of low perfusion.

Adult↗

Evaluation of the newborn mouse model for chemical tumorigenesis.

A total of 45 chemicals, including two aromatic hydrocarbons, five aromatic amines, three azo dyes, ten nitroso compounds, three steroids, four tryptophan metabolites and their related compounds, four naturally occurring substances, four pyrolysates of amino acids and ten miscellaneous compounds, were tested for newborn mouse tumorigenesis assay (NMTA). The results of the NMTA were compared with data from 'Survey of Compounds Which Have Been Tested for Carcinogenic Activity', NIH, NCI, USA (SCWHBTCA), and also with data from the IARC Monographs (Vols 1-41), Lyon, France (IARC). Of the 45 chemicals tested by the NMTA, 28 chemicals showed positive results in the NMTA, and the remaining 17 chemicals were found to be negative for tumor development. The correlation of the results between the NMTA and the mouse and/or rat carcinogenesis test starting at young adult age reported in the SCWHBTCA and in the IARC were compared with 37 chemicals tested; the remaining eight chemicals were found only in our NMTA results. It can be concluded that 31 out of 37 chemicals (83.8%) tested by the NMTA showed similar carcinogenic or non-carcinogenic results obtained in either adult mouse and/or rat carcinogenesis tests. The remaining six chemicals showed contradictory results between the NMTA and either adult mouse and/or rat carcinogenesis tests. Those six chemicals were N-hydroxy-4-acetylaminobiphenyl, estradiol, 3-hydroxyanthranilic acid, 3-hydroxy-L-kynurenine, isonicotinic acid hydrazide and phenobarbital. Among the 37 chemicals, 34 were comparable with the results of the adult mouse carcinogenesis test and those of the NMTA. Twenty-nine out of 34 chemicals (85.3%) showed similar results to the adult mouse carcinogenesis test. Contradictory results were obtained with the following five chemicals: N-hydroxy-acetylaminobiphenyl, 3-hydroxy-anthranilic acid, 3-hydroxy-L-kynurenine, isonicotinic acid hydrazide and phenobarbital. There were 35 chemicals which were comparable with the results of the adult rat carcinogenesis test, and 32 chemicals showed the same results as the NMTA (91.4%). Dissimilar results were obtained with the following three chemicals: estradiol, 3-hydroxy-anthranilic acid and phenobarbital. Based on the results presented in this report, it is reasonable to conclude that the NMTA is one of the most useful and reliable methods for detecting tumorigenic or non-tumorigenic chemicals, when a small amount of chemical is available for rodent carcinogenesis test and the duration of the study is limited to 1 year.

Animals↗

Anticataractogenic property of gamma-glutamylcysteine ethyl ester in an animal model of cataract.

The anticataractogenic potential of gamma-glutamylcysteine ethyl ester was investigated in model cataracts induced by L-buthionine sulfoximine. Subcutaneous injection of the ester (0.625-2.5 mmol/kg) effectively inhibited cataractogenesis in suckling mice. Treatment of mice with L-buthionine sulfoximine alone resulted in a marked reduction of the glutathione content in the eyes. This deprivation of glutathione was mitigated, to a significant degree, by coadministering gamma-glutamylcysteine ethyl ester. In an experiment with rat lens in culture, gamma-glutamylcysteine ethyl ester was found to elevate the lenticular level of glutathione. These results indicate that gamma-glutamylcysteine ethyl ester is able to permeate across biomembranes and serves as an excellent precursor for glutathione biosynthesis, thereby exerting its anticataractogenic activity.

Animals↗

Glutathione and glutathione-related enzymes in human cataractous lenses.

Glutathione and its related enzymes were measured for normal and cataractous human lenses. Glutathione decreased progressively with the development of cataracts. This decrease was more pronounced in the nucleus than in the capsule-epithelia of cataractous lenses. Glutathione reductase in nuclear extracts was relatively unchanged during cataract progress, while glutathione synthetase was significantly low in the advanced stages of cataracts. gamma-Glutamylcysteine synthetase was not measurable in the nuclei of cataractous lenses.

Aged↗

Flow-mediated dilatation of the basilar artery in vivo.

Flow-mediated dilatation has been described mainly in peripheral conduit arteries. The goal of this study was to examine mechanisms and functional implications of flow-mediated dilatation in large cerebral arteries in vivo. Vessel diameter and velocity of blood flow through the basilar artery were measured using a cranial window in 45 anesthetized rats. Mean blood flow velocity through the basilar artery increased by 94 +/- 8% during unilateral common carotid artery occlusion and 203 +/- 13% during bilateral occlusion. Diameter of the basilar artery increased by 10 +/- 1% during unilateral common carotid artery occlusion and 29 +/- 2% during bilateral occlusion from control diameter of 275 +/- 8 microns. Vasodilatation appeared with a delay of 13 +/- 1 seconds after the onset of the increase in flow velocity. With systemic arterial pressure maintained at baseline levels, pressure in the basilar artery (servonull) decreased initially during carotid occlusion, and during dilatation of the basilar artery, pressure was restored partially toward normal. Indomethacin (10 mg/kg i.v.), topical application of tetrodotoxin (10(-6) M), NG-monomethyl L-arginine (5 x 10(-6) M), tetraethylammonium chloride (10(-2) M), glibenclamide (10(-5) M), SKF 525A (3 x 10(-5) M), and ouabain (10(-5) M) had no effect on flow-mediated dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role of the basilar artery in regulation of blood flow to the brain stem in rats.

Large arteries contribute to the regulation of cerebral blood flow. The goal of this study was to examine the effects of changes in diameter of the basilar artery on blood flow to the brain stem. We measured blood flow with laser-Doppler flowmetry in anesthetized rats. The topical application of 10(-6) M serotonin, which selectively constricts large arteries, reduced diameter of the basilar artery by 47 +/- 5% (mean +/- SEM, n = 6) but did not alter blood flow to the ventral brain stem (change in blood flow -2 +/- 5%). The topical application of 10(-8) M vasopressin, which affects both large and small vessels, decreased blood flow by 33 +/- 4% (n = 6). In rats with spontaneous vasomotion, the basilar artery showed rhythmic changes in diameter at a frequency of 4.0 +/- 0.1 cycles/min and an amplitude of 20 +/- 1% of mean diameter (n = 6). Blood flow to the ventral brain stem cycled at the same frequency as and in phase with changes in diameter of the basilar artery, with an amplitude of 15 +/- 1%. We conclude that constriction of the basilar artery may occur with no change in brain stem perfusion. The distinct changes in blood flow during spontaneous vasomotion suggest that vasomotion occurs in intraparenchymal arterioles as well as in the basilar artery.

Animals↗

Pathogenesis of a newly isolated rat virus in newborn and juvenile rats.

The pathogenesis of the UT-1 strain, a newly isolated rat virus (RV), in juvenile and newborn rats was examined. Intracerebrally (ic) inoculated newborns developed severe pantropic infections resulting in emaciation, stunted growth, diarrhea, dehydration and icterus, and died 13 to 15 days after the inoculation. Newborns inoculated intraperitoneally (ip) developed similar, but milder diseases. The virus replicated in all the organs tested, which was followed by severe viremia. Histopathologically, diffuse vacuolation and necrosis of the hepatocytes were observed in the liver. Juvenile rats inoculated with the virus showed neither clinical signs nor histopathologic lesions, although viral recovery and antibody production were observed. Thus, we conclude that the UT-1 strain of RV caused asymptomatic infections in juvenile rats, and fatal infections with hepatic lesions in newborn rats.

Age Factors↗

Hemifacial spasm caused by CP angle AVM associated with ruptured aneurysm in the feeding artery--case report.

A 66-year-old male presented with clinical features of hemifacial spasm. Cerebral angiograms disclosed an arteriovenous malformation (AVM) in the cerebellopontine angle. The hemifacial spasm was caused by a dilated feeding artery of the AVM compressing the facial nerve at the root exit zone. Surgery was not initially performed because of his age and absence of AVM rupture. However, the AVM was associated with a small aneurysm in the feeding artery, which rapidly grew during 20 days after discharge and ruptured causing subarachnoid hemorrhage. The aneurysm was clipped and the feeding artery of the AVM partially obliterated. Careful angiographic examination for associated aneurysms and consequent surgical obliteration to prevent hemorrhage are suggested in cases of AVM.

Aged↗

Brain stem glioma: the role of a biopsy.

A retrospective review of the clinical and histopathological features of 31 patients with brain stem gliomas treated between 1965 and 1990 at Kyushu University Hospital was performed to determine the role of biopsy on these lesions. These 16 male and 15 female patients ranged in age from 3 to 50 years at diagnosis (average: 18.1 years). The primary site of the tumour was the pons in 20 patients, followed by the medulla oblongata and midbrain, and the final histological diagnoses of the lesions based on either the biopsy or autopsy materials were grade I astrocytomas in five patients, grade II in nine, grade III in 10, grade IV in five, and ependymoma in two patients. No consistent correlation could be obtained between the CT findings and histological diagnoses. Open surgical posterior fossa exploration was performed on 17 patients (diagnostic biopsy: 10; volume reduction by tumour removal with or without cyst evacuation: 7) and stereotaxic biopsy on three patients, without any mortality related to these procedures. In our biopsy series, half of the patients with grade II astrocytoma died within 12 months after diagnosis, whereas three out of four patients with grade I astrocytoma survived more than 10 years after diagnosis. Because of the relative safety of the tissue sampling technique, and the importance of an accurate diagnosis in order to select appropriate treatment modalities, histological verification of the lesion should be considered for all patients harbouring a brain stem mass lesion.

Adolescent↗

[Inferior vena caval resection for renal cell carcinoma: usefulness of renal venous pressure measurement].

Renal cell carcinoma with extended tumor thrombi densely adherent to the vena caval wall sometimes requires vena caval resection. If the tumor is on the right side and the collateral veins of the left renal vein are abundant, vena caval reconstruction may not be required. We recently performed radical nephrectomy and vena caval resection on 2 right renal cell carcinoma patients. To decide the necessity of vena caval reconstruction, left renal vein pressure was measured before and after clamping of the vena cava. In case 1, because the pressure was elevated from 21 cmH2O, to 61 cmH2O, total replacement with Gore-Tex graft was performed. In case 2, because the pressure change was from 22 cmH2O to 23 cmH2O, reconstruction was not performed. The most important test to decide the necessity of vena caval reconstruction is thought to be the change of renal venous pressure before and after clamping of the vena cava.

Aged↗

[Contrast echocardiographic assessments of myocardial blood flow in acute myocardial infarction].

Clinical information on the regional myocardial blood flow in the post-ischemic myocardium has been limited. In the present study, we assessed the influence of early coronary reperfusion and coronary obstruction that remained after reperfusion on regional myocardial perfusion by myocardial contrast echocardiography. The study population consisted of 17 patients with acute myocardial infarction who underwent either successful PTCR or emergent PTCA within 6 hours after the onset of the symptom. Myocardial blood flow was visualized by selective injections of hand-agitated poly-gelin colloid solutions into the right and left coronary arteries before and after coronary reperfusion. Before coronary reperfusion, the area at risk for necrosis was defined as the area of contrast defects by the intracoronary injection of contrast medium. The size (severity) of this defect correlated with the anatomic distribution of the obstructed coronary artery. Immediately after emergent PTCA (mean residual stenosis = 25%), 2 of 10 patients still showed injected contrast medium, however, in the remaining 8 patients (80%), the contrast washout time in the risk area was 1.5 times (mean value) longer than that in the normal region. This indicated impairment of the microcirculation in the post-ischemic myocardium. Immediately after PTCR (mean residual stenosis = 89%, p < 0.01 vs PTCA), contrast enhancement was observed only in the peripheral region of the risk area; contrast defects at the center of this region were observed on contrast echocardiography after reperfusion for all patients. This showed that there was impairment of myocardial blood flow in the risk area, even after successful recanalization in patients undergoing PTCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

[Quantification of mitral regurgitation by Doppler color flow mapping: comparison of mitral regurgitant fraction and volume with Doppler measurements].

Color flow imaging of the regurgitant areas has been used to quantitate the severity of valvular regurgitation, however, the exact relationship between color flow areas and regurgitant volumes or fraction has not been clarified. This study was designed to determine whether measurements of jet flow areas and distances using color flow imaging are closely related to the regurgitant volume (MRV:ml/beat) and fraction (MRF: %). Doppler examinations were performed in 29 patients with mitral regurgitation (MR). The MR jet was depicted as the largest clearly definable flow disturbance on the echo images, and the maximal jet area (cm2) and length (cm) were measured. The MRV and MRF were obtained from the Doppler measurements of the transmitral flow (TMF) and the aortic flow (AF) as follows: MRV = TMF-AF, MRF = MRV/TMF x 100. The maximal jet area showed significant correlations with the MRV and MRF (r = 0.75 and 0.75, p < 0.01), and the maximal jet length showed even better correlations with the MRV and MRF (r = 0.82 and 0.80, p < 0.01), irrespective of the etiology of MR. Thus, both the maximal jet area and length obtained from color flow imaging can be simple and useful measurement methods for predicting the MRV and MRF.

Blood Flow Velocity↗

Dose-related sevoflurane metabolism to inorganic fluoride in rabbits.

Serum concentrations and urinary excretion of inorganic fluoride (fluoride ion), a metabolite of sevoflurane, were measured by an ion-chromatographic analyzer after inhalation of three different concentrations of sevoflurane in adult, male Japanese white rabbits weighing 2.6-3.6 kg. Sevoflurane was administered at concentrations of 0% (control), 1%, 2% and 3% (Groups I, II, III and IV, respectively) through a sevoflurane vaporizer for 2 hr under controlled ventilation. Blood and urine samples were collected during and after termination of sevoflurane inhalation at scheduled time intervals for 24 hr. The total volume of urine, the urinary pH and the osmolality of serum and urine were not significantly different among any of the groups. Osmolality of the serum and urine was within normal range in all groups of animals. The mean serum peak values of fluoride ion were 0.7 +/- 0.5, 22.8 +/- 8.7, 31.8 +/- 11.0 and 41.5 +/- 13.2 microM (mean +/- SD) in groups I, II, III and IV, respectively. Peak values were recorded within 15 min after the termination of inhalation. The cumulative amounts of fluoride ion excreted in urine in 24 hr were calculated to be 5.0 +/- 1.6, 26.1 +/- 6.7, 41.4 +/- 11.3 and 64.3 +/- 18.0 mumol (mean +/- SD) in groups I, II, III and IV, respectively. Regression analysis revealed significant correlations between the formation and excretion of fluoride ion, and the dose of sevoflurane (r = 0.85, p less than 0.05 and r = 0.89, p less than 0.05, respectively). The authors conclude that the formation and excretion of fluoride ion after sevoflurane anesthesia is dependent on the dose of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Aerobic dehalogenation of halothane showing different substrate dependency from anaerobic dehalogenation in liver microsomes of guinea pig.

The formation of trifluoroacetic acid (TFAA) from halothane under aerobic conditions and that of chlorotrifluoroethane (CTE) and chlorodifluoroethylene (CDE) from halothane under anaerobic conditions were studied using guinea pig liver microsomes. The formation of TFAA was inhibited by specific inhibitors of cytochrome P450 (P450), such as carbon monoxide and metyrapone and was dependent upon P450 contents. The maximum activity of the TFAA formation was obtained at pH 6.0. On the other hand, the maximum activity to form CTE and CDE was obtained at pH 7.4. The formation of TFAA reached a plateau at a halothane concentration above 0.17 mM, but the rate of formation of CDE and CTE was dependent upon a halothane concentration up to 1.5 mM. The values of apparent Michaelis-Menten constant (Km) and maximum velocity (Vmax) for TFAA formation were 0.067 mM and 0.349 nmol/nmol P450/min respectively, those for CDE formation were 0.983 mM and 0.326 nmol/nmol P450/min respectively, and those for CTE formation were 1.71 mM and 0.752 nmol/nmol P450/min respectively. These results showed clearly that the formation of TFAA, CDE and CTE was catalyzed by the P450 system in guinea pig liver microsomes. Under optimal conditions, saturation was observed in the formation of TFAA from halothane at a halothane concentration above 0.17 mM but the formation of CDE and CTE was not saturated at this concentration, and the value of apparent Km for TFAA formation was lower than those for CDE and CTE formation.

Aerobiosis↗