Search PubMed⌕ Search

Biomedical subjects

T Sakaki

Publications and source records attributed to T Sakaki.

At least 55 records · Page 3Linked to original sources
PubMed2000

Metabolism of vitamin D(3) by human CYP27A1.

Human vitamin D(3) 25-hydroxylase (CYP27A1) cDNA was expressed in Escherichia coli, and its enzymatic properties were revealed. The reconstituted system containing the membrane fraction prepared from the recombinant E. coli cells was examined for the metabolism of vitamin D(3). Surprisingly, at least eight forms of metabolites including the major product 25(OH)D(3) were observed. HPLC analysis and mass spectrometric analysis suggested that those metabolites were 25(OH)D(3), 26(OH)D(3), 27(OH)D(3), 24R,25(OH)(2)D(3), 1alpha, 25(OH)(2)D(3, )25,26(OH)(2)D(3) (25,27(OH)(2)D(3)), 27-oxo-D(3) and a dehydrogenated form of vitamin D(3). These results suggest that human CYP27A1 catalyzes multiple reactions and multiple-step metabolism toward vitamin D(3). The K(m) and V(max) values for vitamin D(3) 25-hydroxylation and 25(OH)D(3) 1alpha-hydroxylation were estimated to be 3.2 microM and 0.27 (mol/min/mol P450), and 3.5 microM and 0.021 (mol/min/mol P450), respectively. These kinetic studies have made it possible to evaluate a physiological meaning of each reaction catalyzed by CYP27A1.

Base Sequence↗
PubMed2000

Effects of acidosis on the post-hypoxic recovery of synaptic transmission in gerbil hippocampal slices.

We investigated the effects of acidosis on the hypoxic neuronal damage using gerbil hippocampal slices. Acidosis has delayed the onset of harmful hypoxic depolarization, resulting in a decrease in the total hypoxic period and the hypoxic depolarization. This effect has been considered to be protective. However, the synaptic recovery after reoxygenation was attenuated when acidosis (pH: 6.2-6.9) was sustained. Conversely, the synaptic recovery was potentiated when the acidosis was restored to the physiological milieu during the reoxygenation period. These results suggest that acidosis plays a protective effect against the hypoxic neuronal damage only when rapid appreciable pH recovery is achieved during reoxygenation.

Acidosis↗
PubMed2000

Low dose propofol as a supplement to ketamine-based anesthesia during intraoperative monitoring of motor-evoked potentials.

STUDY DESIGN: Motor-evoked potentials (MEPs) were analyzed using transcranial electrical stimulation during spinal surgery in patients under ketamine-based anesthesia, with and without propofol. OBJECTIVE: To investigate the effects of propofol on MEPs and ketamine-induced adverse effects during spinal surgery in patients under ketamine-based anesthesia. SUMMARY OF BACKGROUND DATA: Intraoperative monitoring of transcranial motor-evoked responses provides a method for monitoring the functional integrity of descending motor pathways. However, because these responses are sensitive to suppression by most anesthetic agents, anesthetic technique is limited during the monitoring of MEPs. Ketamine has been reported to have little effect on MEPs but may produce adverse effects such as psychedelic effect and hypertension. Recently, it has been reported that propofol may be able to inhibit ketamine-induced adverse effects. METHODS: Intraoperative monitoring of MEPs was performed in 58 patients who underwent elective spinal surgery. Anesthesia was maintained with nitrous oxide-fentanyl-ketamine without or with low-dose (1-3 mg/kg/hr) of propofol (K group; n = 34, KP group; n = 24, respectively). Transcranial stimulation with single or paired pulses or a train of three or five pulses (interstimulus interval, 2 msec) were delivered to the scalp, and compound muscle action potentials were recorded from the left and right tibialis anterior muscles. To investigate the dose effects of propofol on MEPs, propofol was administered at an infusion rate of 6, 4, and 2 mg/kg/hr and then discontinued in 14 patients. RESULTS: Results of MEPs were comparable between the K and KP groups. The incidence of postoperative psychedelic effect was significantly less in the KP group (14%) than in the K group (41%). Although propofol inhibited MEPs dose dependently, the use of a train of pulses for stimulation could overcome such inhibition. CONCLUSIONS: If a train of pulses were used for transcranial stimulation, low-dose propofol can be effectivelyused as a supplement to ketamine-based anesthesia during intraoperative monitoring of myogenic MEPs. Addition of propofol significantly reduced the ketamine-induced psychedelic effects.

Adolescent↗
PubMed2000

Application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to insoluble glucose oligomers in decomposed cellulose.

An analytical approach is described for the molecular weight characterization of glucose oligomers from cellulose which had been decomposed by hot-compressed water (HCW). Microcrystalline cellulose was decomposed to 18% of water insoluble fraction (WI) plus 82% of water soluble fraction (WS) by HCW (295 degrees C, 10 mL/min). The glucose oligomers in the WI were analyzed by pericullar anion exchange chromatography, and oligomers longer than pentamers were detected. These results were also confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Many peaks derived from glucose oligomers with molecular weights less than 4000 Da were detected in the spectra. Mass differences between peaks were 162 Da, as expected for polymers composed of glucose units. This appears to be the first report concerning molecular weight determination of water or organic solvent insoluble compounds like glucose oligomers from cellulose using MALDI-TOFMS.

Cellulose↗
PubMed2000

Miniaturization of capillary electrochromatography using an ultrashort capillary column.

The instrumentation for miniaturization of capillary electrochromatography was devised and an injection method for this apparatus was proposed. By using an ultra short capillary column (15 mm packed length, 36 mm total length, 75 microm inner diameter, packed with cation exchange supports), the separation of five biochemical compounds was performed within 1 min. The high separation efficiency of 9780 plates was achieved by using an ultrashort capillary column. The miniaturized instrumentation for capillary electrochromatography might be utilized as one of the possible methods in microfabricated analysis or in an alternative approach to it.

Biochemistry↗
PubMed2000

Chemical preconditioning with 3-nitropropionic acid in gerbil hippocampal slices: therapeutic window and the participation of adenosine receptor.

Ischemic tolerance induced by a subtoxic dose of neurotoxin, 3-nitropropionic acid (3-NPA), was recently reported as "chemical preconditioning." We electrophysiologically investigated the therapeutic window and the effect via action at the adenosine receptor using a gerbil hippocampal slice model of the tolerance phenomenon. 3-NPA at the dose of 4 mg/kg was administered intraperitoneally at 3, 24, and 72 h prior to slice preparation. Prolonged delay to hypoxic depolarization (HD) and improvement of the field excitatory postsynaptic potential recovery following a fixed period of hypoxia (8 min) were observed in the groups pretreated at 3 and 24 h compared with the control (P < 0.05). Correlation between the delay to HD and the recovery was highly significant (r = 0.37, P < 0.001). These effects were completely reversed by administration of theophylline (20 mg/kg), an adenosine receptor blocker. These findings indicate that chemical preconditioning with 3-NPA induces early onset (3 h) and long-lasting (24 h) tolerance of hypoxic damage to excitatory synaptic mechanisms in the hippocampus by delayed calcium entry, and the activation of adenosine receptor contributes to this neuroprotective effect.

Adaptation, Physiological↗
PubMed2000

Relation between myocardial response to dobutamine stress and sympathetic nerve activation in patients with idiopathic dilated cardiomyopathy: a comparison of 123I-MIBG scintigraphic and echocardiographic data.

It is likely that a close association exists between findings obtained by two methods: dobutamine stress echocardiography and 123I-MIBG scintigraphy. Both of these methods are associated with beta-adrenergic receptor mechanisms. This study was conducted to demonstrate the relation between myocardial response to dobutamine stress and sympathetic nerve release of norepinephrine in the failing heart. In 12 patients with heart failure due to idiopathic dilated cardiomyopathy, the myocardial effects of dobutamine stress were evaluated by low-dose dobutamine stress echocardiography: and sympathetic nerve function was evaluated by scintigraphic imaging with iodine-123 [123I] meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine. Echocardiography provided quantitative assessment of wall motion and left ventricular dilation; radiotracer studies with 123I-MIBG provided quantitative assessment of the heart-to-mediastinum (H/M) uptake ratio and washout rate. Results showed that H/M correlated with baseline wall motion (r = 0.682, p = 0.0146), wall motion after dobutamine stress (r = 0.758, p = 0.0043), the change in wall motion (r = 0.667, p = 0.0178), and with left ventricular diastolic diameter (r = 0.837, p = 0.0007). In addition, the 123I-MIBG washout rate correlated with baseline wall motion (r = 0.608, p = 0.0360), wall motion after dobutamine stress (r = 0.703, p = 0.0107), and with the change in wall motion (r = 0.664, p = 0.0185). Wall motion, especially in the myocardial response to dobutamine stress, is related to sympathetic nerve activity in heart failure.

3-Iodobenzylguanidine↗
PubMed2000

Impact of anatomical difference of the cerebral venous system on microcirculation in a gerbil superior sagittal sinus occlusion model.

Sinus-vein thrombosis (SVT) is known to have a wide spectrum of clinical manifestations, and the formation of venous collateral pathways is considered to be one of the most important factors influencing the individual outcome. Here, we examined the relationship between the anatomical differences in bridging veins and cerebral microcirculation in a gerbil superior sagittal sinus (SSS) occlusion model. In male Mongolian gerbils (n=26), the SSS was ligated close to the confluence sinuum. Four additional animals served as the sham-operated control. Regional cerebral blood flow (rCBF) and haemoglobin oxygen saturation (HbSO2) were assessed by Laser-Doppler flowmetry and a microspectrophotometric method at 36 identical locations in the both hemispheres every 20 minutes for 120 minutes after ligation using a "scanning" technique. Furthermore, we examined change in the diameter of the bridging vein by fluorescence angiography and brain damage by histological investigation after 48 hours. Based on the anatomical findings, the hemispheres were classified into two groups: group A with one bridging vein, n=24/52 sides (46.2%) and group B with more than two bridging veins, n=28/52 sides (53.8%). Significant decreases in rCBF (P<0.05) and rHbSO2 (P<0.05) were seen from 20 minutes after the ligation to the end of the experiment in group A, but not in group B. A detailed analysis of individual cases in changes of local (l) CBF and lHbSO2 revealed three patterns: 1) pattern-1, no change; 2) pattern-2, decrease with following recovery; 3) and pattern-3, decrease without recovery. There were no significant differences in the diameter of the bridging vein and no venous infarction in either groups. The group A frequency, which consisted of pattern-3 (58.3%)>pattern-2 (29. 2%)>pattern-1 (12.5%), was opposite to that of group B, which consisted of pattern-1 (71.4%)>pattern-2 (25.0%)>pattern-3 (3.6%) (P<0.001). Based on the results of this study, the anatomical structure and an opening of the collateral pathways of the venous drainage system are closely related to microcirculatory alterations after venous occlusion. The experimental model is suitable for the study of the pathophysiological mechanism responsible for the high variability of SVT.

Animals↗
PubMed2000

Wall imaging of cerebral aneurysms with a modified surface-rendering technique of spiral CT.

BACKGROUND: There has been no detailed documentation of the advantages of three-dimensional (3D) wall imaging of cerebral aneurysms. The usefulness of such endoscopic images obtained with modified spiral computed tomography angiography (CTA) was therefore examined in comparison with conventional spiral CTA and digital subtraction angiography (DSA). METHODS: Fifteen of 45 patients who underwent conventional spiral CTA in our department in the past 4 years, were further studied with a technical modification of surface-rendering reconstruction in spiral CT. Endoscopic images were obtained by regulating the lower and higher thresholds of spiral CT scans in processing. Digital subtraction angiography was also performed for 14 of the 15 patients. The 3D wall images of the cerebral aneurysms were assessed in comparison with findings from conventional CTA and DSA. FINDINGS: The true orifice of the aneurysms could be visualized with the endoscopic mode in all of the 15 cases. In paraclinoid aneurysms, particularly below the anterior clinoid process, the relationships to associated vessels and bone structures were more clearly disclosed with this mode. The endoscopic images of aneurysms with rigid clots or neighboring distended veins were not as adversely affected as conventional CTA. In 4 of the 15 the wall imaging precisely located the branches arising from the dome of aneurysms which DSA could not. INTERPRETATION: Wall imaging of complex or small cerebral aneurysms provided valuable information on their relationships to associated arteries and surrounding bony structures. The endoscopic mode, a simple modification of surface rendering, is easily available in commercial CT processing packages.

Adult↗
PubMed2000

Dual metabolic pathway of 25-hydroxyvitamin D3 catalyzed by human CYP24.

Human 25-hydroxyvitamin D3 (25(OH)D3) 24-hydroxylase (CYP24) cDNA was expressed in Escherichia coli, and its enzymatic and spectral properties were revealed. The reconstituted system containing the membrane fraction prepared from recombinant E. coli cells, adrenodoxin and adrenodoxin reductase was examined for the metabolism of 25(OH)D3, 1alpha,25(OH)2D3 and their related compounds. Human CYP24 demonstrated a remarkable metabolism consisting of both C-23 and C-24 hydroxylation pathways towards both 25(OH)D3 and 1alpha,25(OH)2D3, whereas rat CYP24 showed almost no C-23 hydroxylation pathway [Sakaki, T. Sawada, N. Nonaka, Y. Ohyama, Y. & Inouye, K. (1999) Eur. J. Biochem. 262, 43-48]. HPLC analysis and mass spectrometric analysis revealed that human CYP24 catalyzed all the steps of the C-23 hydroxylation pathway from 25(OH)D3 via 23S, 25(OH)2D3, 23S,25,26(OH)3D3 and 25(OH)D3-26,23-lactol to 25(OH)D3-26, 23-lactone in addition to the C-24 hydroxylation pathway from 25(OH)D3 via 24R,25(OH)2D3, 24-oxo-25(OH)D3, 24-oxo-23S,25(OH)2D3 to 24,25,26,27-tetranor-23(OH)D3. On 1alpha,25(OH)2D3 metabolism, similar results were observed. These results strongly suggest that the single enzyme human CYP24 is greatly responsible for the metabolism of both 25(OH)D3 and 1alpha,25(OH)2D3. We also succeeded in the coexpression of CYP24, adrenodoxin and NADPH-adrenodoxin reductase in E. coli. Addition of 25(OH)D3 to the recombinant E. coli cell culture yielded most of the metabolites in both the C-23 and C-24 hydroxylation pathways. Thus, the E. coli expression system for human CYP24 appears quite useful in predicting the metabolism of vitamin D analogs used as drugs.

Adrenodoxin↗
PubMed2000

Spinal dural arteriovenous fistula with perimesencephalic subarachnoid haemorrhage.

A case is reported of a 66 year old woman presenting with perimesencephalic subarachnoid haemorrhage (SAH) which was caused by a spinal dural arteriovenous fistula at the C1 level. The fistula drained into the venous system of the posterior cranial fossa through a perimedullary vein. The bleeding was thought to result from venous hypertension induced by the fistula. This case may support the hypothesis that perimesencephalic non-aneurysmal SAH can be ascribed to venous bleeding and that venous hypertension is the key to its pathology.

Aged↗
PubMed2000

Extensive cervical laminoplasty for patients with long segment OPLL in the cervical spine: an alternative to the anterior approach.

We investigated treatment of long segment cervical OPLL by posterior decompression using a laminoplasty technique. Our aim was to both decompress the spinal cord and also to preserve neck motion. There were 38 patients treated by this posterior approach. Twenty-eight patients underwent C1-C7 expanding laminoplasty, 4 patients underwent C1-T1 expanding laminoplasty, and 6 patients C2-C7 expanding laminoplasty. The transverse width of the open-door laminoplasty was sufficient to achieve decompression of not only the spinal cord but also the nerve root outlets at each laminoplasty level. There were no complications related to this surgical technique, nor late deterioration in the mean follow up period of 4. 5 years. We propose expanding laminoplasty as an important option for the treatment of long segment cervical OPLL.

Decompression, Surgical↗
PubMed2000

Surgical management of cerebral arteriovenous malformations with intraoperative digital subtraction angiography.

Complete excision of cerebral arteriovenous malformations (AVMs) is requisite to improving the outcome of patients with AVMs. Five patients with a small or medium cerebral AVM underwent surgery with an intraoperative digital subtraction angiography (DSA) unit. There were no residual AVMs and no complications in the examination of intraoperative DSA. The findings of postoperative angiography were consistent with those of intraoperative DSA. Intraoperative DSA provided the benefits of not only identification of a feeding artery, but also recognition of the complete excision during surgery.

Adolescent↗
PubMed2000

Surgery for dural arteriovenous fistula in superior sagittal sinus and transverse sigmoid sinus.

The aim of this study was to evaluate the outcome of surgically treated dural arteriovenous fistula (DAVF). The authors performed surgical removal of DAVF in 12 patients. The locations of DAVF were the transverse sigmoid sinus in seven patients and superior sagittal sinus in five patients. These 12 patients had undergone endovascular embolisation prior to removal. Among them, six patients were completely cured, according to angiography immediately after embolisation, but these six patients showed the recurrence of DAVF within 1 year. The other six patients showed a decrease of feeding vessels. Therefore, all 12 patients underwent surgical removal of DAVF. The surgical strategies were as follows. The feeding vessels and the cortical veins with retrograde filling were occluded and cut. The affected sinus was skeletonised, and if it was occluded or almost occluded, the sinus was removed. Postoperatively, transient aphasia was seen in one patient. There was no surgical morbidity or mortality. During the follow-up period (mean 2.9 years), no recurrence of DAVF was seen. Surgical treatment is a safe and effective treatment manoeuvre for DAVF around the transverse sigmoid sinus and superior sagittal sinus.

Adult↗
PubMed2000

Effect of stimulation of the dorsal aspect of the cervical spinal cord on local cerebral blood flow and EEG in the cat.

Currently there is considerable interest in electrical stimulation of the dorsal aspect of the cervical spinal cord as a potentially effective therapy for persistent vegetative patients. The authors assessed change in the local cerebral blood flow (LCBF) and electroencephalogram (EEG) in the cat following spinal cord stimulation (SCS). In 31 adult cats under isoflurane anesthesia, an electrode for SCS was introduced epidurally to the midline of the C2-C3 segment. Stimulation was performed at 25 Hz and 0.1 msec for 30 min. These animals were divided into five groups by the voltage: (1) 2V (n = 7), (2) 4V (n = 7), (3) 6V (n = 7), (4) 4V with intravenous injection of muscarinic cholinergic agents--atropine sulfate (n = 5), and (5) sham-operated control (n = 5) without stimulation. LCBF was measured by laser Doppler flowmetry through bilateral small burr holes at the parietal area during and 60 min after stimulation. At 2V, LCBF increased only during SCS, then returned to the pre-stimulated level, while the increase continued until the end of the experiment at 4V and 6V. The increase in LCBF was not affected by atropine sulfate. EEG showed spike and wave or polyspikes after SCS in two animals of the 6V group, but not in the 2V and 4V groups, and moreover a moderate increase of the background activity at only 4V. The present data suggested that SCS at 4V can provide the appropriate microcirculatory enhancement with less harmful influence which continues to increase 30 min after SCS, although the exact mechanism should be elucidated continuously. Within the limitation of animal experiments, this study could provide the logical basis for determining the condition of SCS.

Acetylcholine↗
PubMed2000

The effect of brain compression under venous circulatory impairment.

It is well known that surgical obliteration of the cerebral veins with additional brain compression by retractors is dangerous. To evaluate the mechanism, we studied the change in cerebral microcirculation and parenchymal damage following brain compression with venous circulatory impairment using a rat model. The animals were divided into the following four groups (each n = 5) (1) a sham-operated control; (2) group A, one cortical vein occlusion; (3) group B, a 30 mmHg compression pressure; and (4) group C, one cortical vein occlusion with 30 mmHg compression. The cortical vein was occluded photochemically. Local cerebral blood flow (l-CBF) in the compressed area was measured by stationary laser-Doppler (LD) flowmetry and regional CBF (r-CBF) in the surrounding area was also measured by LD scanning technique for 120 min. l-CBF in the compressed area decreased significantly in groups B and C. A gradual and significant increase in group B and decrease in group C in r-CBF of the surrounding area were observed. Histologically, more extensive damage was observed in group C than in group A and B. The degree of hypoperfusion of the affected brain correlated well with the subsequent brain damage in the experiments. We demonstrated that, compared with vein occlusion or brain compression alone, the accumulated episode caused severe ischemia, then increased the vulnerability of the rat brain to tissue damage.

Animals↗
PubMed2000

Analysis of prognostic and survival factors related to treatment of low-grade astrocytomas in adults.

Prognostic factors for low-grade astrocytomas have been proposed, but optimal treatment remains controversial. Eighty-eight consecutive adult patients with supratentorial low-grade astrocytomas were retrospectively reviewed to determine specific factors influencing outcome. All underwent craniotomy (43 radical resections, 45 nonradical resections). Sex, age at diagnosis, preoperative Karnofsky performance status (KPS), tumor location, estimated extent of resection, radiation, chemotherapy, histological type, p53 status, MIB-1 staining and the apoptotic index were assessed as parameters for prognostic significance. KPS (p = 0.03), tumor location (p < 0.001), extent of surgical resection (p < 0.001) and radiotherapy (p = 0.01) were significantly associated with longer survival rates by univariate analysis. Multivariate analysis also showed a significant correlation between radiation therapy after surgical removal and survival time (p < 0.001). p53 status was not of importance in determining the necessity for radiotherapy. Radical surgical removal is the most important factor in the management of low-grade astrocytomas. Radiation therapy appears to be effective in improving the prognosis regardless of the extent of surgical resection or the p53 status.

Adult↗