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T Sakaki

Publications and source records attributed to T Sakaki.

At least 127 records · Page 7Linked to original sources
PubMed1998

Rat CYP24 catalyses 23S-hydroxylation of 26,26,26,27,27,27-hexafluorocalcitriol in vitro.

1. Kidney mitochondrial 24-hydroxylase cytochrome P450 (CYP24) catalyses sequential hydroxylation at both C-24 and C-23 positions of calcidiol and calcitriol. Here, we have investigated the in vitro metabolism of a hexafluorinated derivative of calcitriol, 26,26,26,27,27,27-hexafluorocalcitriol (ST-630), in a reconstituted system by using recombinant Escherichia coli membrane fractions containing rat CYP24. 2. When ST-630 was incubated with CYP24 supplemented with bovine adrenodoxin and NADPH-adrenodoxin reductase, a distinct metabolite could be observed. This metabolite was found to be 26,26,26,27,27,27-hexafluoro-23S-hydroxcalcitriol, a biologically active metabolite of ST-630, based on cochromatography on HPLC and mass spectrometric analysis. 3. These results show the direct evidence that CYP24 plays an essential role in the metabolism of ST-630 to yield its 23S-hydroxylated metabolite, as observed in cultured cells and experimental animal studies.

Adrenodoxin↗
PubMed1998

The effect of lesionectomy and the perilesional GABAergic neuronal changes in alumina cream-induced focal motor epilepsy in cats.

The effect of lesionectomy depends on the reversibility of the epileptogenic changes in the perilesional cortex. We studied how the perilesional GABAergic neuronal changes are related to the effect of lesionectomy in the alumina cream-induced focal epilepsy model in cats. Sequential changes of GABAergic neurons and spike activities were measured after the micro-injections of alumina cream (AC). Alumina granulomas were excised 15 days and 40 days after the injections. At day 20 following the AC injection, GABAergic neurons were decreased 25 to 40% compared with those in the contralateral intact cortex. At day 40, a significant increase of spike activities occurred. GABA positive cells were decreased more than 50% compared with those in the contralateral cortex. At day 80, significant cell loss in perilesional cortex was demonstrated. The effect of lesionectomy was greater in the early excised group than in the late excised group. Decrease of GABAergic neuron was more severe in the late excised group compared to the early excised group. Our results indicate that more than 50% reduction of perilesional GABA neurons may be a critical point in epileptogenesis in this model. Lesionectomy alone prior to a 50% reduction in perilesional GABAergic neurons may be sufficient for seizure control. With these data it is still unclear whether these findings contribute to the choice between lesionectomy alone and lesionectomy with resection of the perilesional cortex. Further study is needed to understand the difference between the AC epilepsy model and human chronic epilepsy.

Aluminum Oxide↗
PubMed1998

Spinal cord blood flow and pathophysiological changes after transient spinal cord ischemia in cats.

OBJECTIVE: The goal was to study the hemodynamics and regional pathophysiological changes in the spinal cord after transient vascular occlusion in cats. METHODS: We measured spinal cord blood flow (SCBF) continuously in the lumbar region with a laser-doppler flowmeter, before, during, and after spinal cord ischemia induced by balloon occlusion of the thoracic aorta, in 24 cats (divided into three groups) and simultaneously recorded the evoked spinal cord potentials (ESPs). In each group (n = 8), 10-, 20-, and 30-minute ischemic loading was performed. All animals were evaluated neurologically 36 hours later, and then their spinal cords were examined histologically. RESULTS: The amplitude of ESPs decreased 10 minutes and disappeared 20 minutes after occlusion. SCBF increased to as much as 2 times the control values after reperfusion and decreased gradually in all groups. Then, in all animals in the 10-minute group and six animals in the 20-minute group, SCBF returned to the control values, which were subsequently maintained throughout the experiment, and ESPs returned to normal patterns within 1 hour. For all animals in the 30-minute group and two in the 20-minute group, hypoperfusion after recirculation, irreversible amplitude changes in ESPs, postischemic paraparesis, and pathological ischemic changes in the lower thoracic and lumbar spinal segments were recognized. CONCLUSION: Our results showed that > 20-minute occlusion of the thoracic aorta in cats resulted in irreversible spinal perfusion disorders and that the monitoring of SCBF and ESPs could be useful for predicting potential neurological deficits. Furthermore, postischemic hypoperfusion may have an important role in the development of secondary spinal cord ischemia, resulting in severe neurological dysfunction. This observation suggested the possibility of therapeutic modification of the secondary processes inducing hypoperfusion after spinal ischemia.

Angiography↗
PubMed1998

The effect of sevoflurane on myogenic motor-evoked potentials induced by single and paired transcranial electrical stimulation of the motor cortex during nitrous oxide/ketamine/fentanyl anesthesia.

To overcome anesthetic-induced depression of myogenic motor-evoked potentials (MEPs), several techniques of stimulation using paired pulses or trains of pulses are used. This study investigated the effect of sevoflurane on myogenic MEPs induced by single and paired transcranial electrical stimulation of the motor cortex. Nine patients undergoing elective spinal surgery were anesthetized with fentanyl-N2O-ketamine. Partial neuromuscular blockade (single-twitch height 15% of baseline) was maintained with vecuronium. Single and paired (interstimulus interval 2 milliseconds) electrical stimuli were delivered to the scalp, and compound muscle action potentials were recorded from the left and right tibialis anterior muscles. In all patients, baseline MEPs were recorded from both the left and right anterior tibialis muscles (in a total of 18 legs). During the administration of 0.25 MAC and 0.5 MAC sevoflurane, MEPs induced by stimulation with a single pulse could be recorded in 12 of 18 and 4 of 18 legs, respectively, and MEP amplitude was significantly reduced to 48% and 4% of the control value, respectively. During the administration of 0.75 MAC sevoflurane, MEPs following single-pulse stimulation could not be recorded in any legs. The success rate of MEP recording during the administration of sevoflurane was greater after paired stimulation than after single stimulation, and percentage MEP amplitude (percentage of the control value after single stimulation but before sevoflurane) after paired stimulation was significantly higher than after single stimulation before and during the administration of 0.25 MAC and 0.5 MAC sevoflurane. The success rate of MEP recording and MEP amplitude after paired stimulation decreased in a dose-dependent manner during the administration of sevoflurane. These results suggest that although facilitation by the second stimulus was considerable, paired stimuli are still not sufficient to overcome the depressant effects of sevoflurane in clinically used concentrations.

Action Potentials↗
PubMed1998

Postlaminectomy cervical spinal cord compression demonstrated by dynamic magnetic resonance imaging. Case report.

This 32-year-old man had undergone C3-7 laminectomy for posttraumatic cervical myelopathy associated with spinal canal stenosis. He developed recurrent myelopathy 5 years after the initial operation. Dynamic magnetic resonance (MR) imaging of the cervical spine demonstrated spinal cord compression with diffuse canal stenosis while the neck was in the extended position, whereas no significant stenosis was visualized in the neutral position. Sagittal and axial MR images of the affected levels demonstrated striking changes in the cervical spinal cord configuration. Because of an associated hard osteophyte formation and protruded disc, as well as a hypertrophied posterior longitudinal ligament, an anterior decompression and fusion with plate fixation were performed from C-4 to C-7. The postoperative course was uneventful, with subsequent neurological improvement. It is concluded that dynamic MR imaging aids the search for the cause of recurrent postlaminectomy cervical myelopathy after initial improvement following decompressive surgery.

Adult↗
PubMed1998

Local cerebral blood flow autoregulation following "asymptomatic" cerebral venous occlusion in the rat.

OBJECT: Maintenance of cerebral blood flow (CBF) autoregulation in the brain is of major importance for patient outcome in various clinical conditions. The authors assessed local autoregulation after "asymptomatic" cortical vein occlusion. METHODS: In Wistar rats, a single cortical vein was occluded photochemically by using rose bengal and fiberoptic illumination. In rats with bilateral carotid artery occlusion, mean arterial blood pressure (MABP) was lowered in 5-mm Hg increments down to 40 mm Hg by using hypobaric hypotension. Local CBF at each pressure level was assessed by performing laser Doppler (LD) scanning at 25 (5 x 5) locations within bilateral cranial windows. In this manner, the lower limit of autoregulation (LLA) was detected. The LLA was 60 mm Hg in both right and left hemispheres in Group A (five rats), in which the animals received illumination without rose bengal and had no venous occlusion. Of the 11 rats that underwent vein occlusion, three developed severe reductions in local CBF and/or a growing venous thrombus and were distinguished as Group C (symptomatic; three rats); from previous work we know that those animals are bound to experience venous infarction. The remaining rats formed Group B (asymptomatic; eight rats). In this group the LLA remained at 60 mm Hg in the left hemisphere without occlusion, whereas, in the right cortex with the occluded vein, the LLA was found to be 65 mm Hg. Below a carotid stump pressure of 25 mm Hg regional CBF in the affected hemisphere dropped more abruptly to a possibly ischemic range than that in the opposite normal hemisphere. CONCLUSIONS: The results of the present study suggest that cerebral venous circulation disorders are manifested via additional pathways, that is, from a partially impaired local autoregulation in the vicinity of the occluded vein, even under conditions in which the vein occlusion itself does not cause brain damage. Care should be taken in the control of blood pressure in patients with this pathological condition.

Analysis of Variance↗
PubMed1998

[Analysis of postoperative shivering following the deliberate mild hypothermia during neurosurgery].

We induced deliberate mild hypothermia in 96 patients who underwent intracranial operations using a water blanket and a convective device blanket. The lowest temperature measured at the tympanic membrane during mild hypothermia was adjusted to 34.5 degrees C. The patients were divided into two groups in respect to the occurrence of postoperative shivering, and the relationship between the perioperative parameters and the occurrence of postoperative shivering was evaluated. Shivering was observed postoperatively in 29 to 96 patients (30.2%). In the group with shivering (SV), age was significantly lower and body weight and body surface area were significantly larger than the group without shivering (NSV). Urinary output was significantly larger in SV than in NSV. Tympanic membrane, nasopharyngeal, and rectal temperatures at the end of surgery and nasopharyngeal, rectal, and peripheral temperatures just after the extubation were significantly lower in SV than in NSV. These results suggest that sufficient rewarming of both the core and peripheral temperatures is important to prevent the postoperative shivering following the mild hypothermic therapy in neurosurgical patients, especially in young patients.

Adult↗
PubMed1997

Retinoblastoma protein expression and MIB-1 correlate with survival of patients with malignant astrocytoma.

BACKGROUND: Regulatory coupling of cell proliferation and apoptosis is suggested by recent findings with regard to certain tumors, such as the finding of tumor resistance to anticancer therapy caused by inhibition of apoptosis. The processes leading to apoptosis appear to be regulated by a variety of oncogenes and tumor suppressor genes. In the current study, the relation between apoptosis and expression of retinoblastoma protein (pRB) was assessed in 50 primary anaplastic astrocytomas (AAs) and 46 recurrent tumors in the same patients as the primary tumors after macroscopic total surgical resection and chemoradiotherapy. METHODS: Apoptotic cells were identified by the in situ 3'-end labeling technique. Proliferative potential, pRB expression, and p53 expression were evaluated immunohistochemically using anti-Ki-67 (MIB-1), anti-pRB, and anti-p53 antibodies, respectively. The prognostic value of these biologic markers in AA patients undergoing treatment was also evaluated. RESULTS: The mean apoptotic index (AI) was 0.91 +/- 0.70% for specimens obtained at the initial surgery and 2.32 +/- 1.71% for those obtained at recurrence. There was no apparent correlation between the AI and the MIB-1 staining index (MI) in primary AAs, whereas significantly higher AI and MI were observed in recurrent pRB negative cases than in their pRB positive counterparts. The survival of patients with AAs showing a high MI and negative pRB immunostaining was significantly shorter than in the other cases. Neither the size of the apoptotic fraction nor the p53 expression in primary tumor correlated with the overall survival. CONCLUSIONS: The clinical outcome of patients with AA may be associated with aberrant pRB function and increased proliferative activity rather than an inability of tumor cells to undergo apoptosis.

Adult↗
PubMed1997

Expression of tPA mRNA in the facial nucleus following facial nerve transection in the rat.

Plasminogen activators (PAs) have been suggested to play a role in neuronal migration and glial cell proliferation in the developing CNS. Less is known, however, about the role of PAs in the mature nervous system. To elucidate the role of tissue type plasminogen activator (tPA) in the nervous system we used in situ hybridization to study the expression of tPA mRNA within the rat facial nucleus after facial nerve transection. We also studied the effect of MK-801 on tPA mRNA expression in order to investigate whether the previously reported N-methyl-D-aspartate (NMDA) receptor activation is involved in this model. tPA mRNA was expressed in the ipsilateral facial motoneurones from 6 h after injury. This expression continued for at least 2 weeks after facial nerve transection. Administration of MK-801 before axonal injury did not affect the expression of tPA mRNA in the facial nucleus. These data suggest that tPA might be involved in the regenerative process without NMDA receptor activation in mature facial neurones.

Animals↗
PubMed1997

Shortened telomere length and increased telomerase activity in hamster pancreatic duct adenocarcinomas and cell lines.

Recently, shortened telomere length and increased telomerase activity have been demonstrated in various human cancers. In the study reported here, we ascertained whether gene changes are characteristic of pancreatic cancers. Hamster duct carcinomas and cell lines were investigated by Southern blot analysis for telomere restriction fragment (TRF) length and by the telomeric repeat amplification protocol (TRAP) assay for telomerase activity. Comparison with normal pancreas and spleen revealed shortened TRF length and markedly increased telomerase activity in primary pancreatic duct carcinomas induced by the rapid-production model as well as in a transplantable carcinoma and the cell lines. The enzyme level was 86.0-215.7 times the low levels found in control pancreas and spleen tissues. Late-passage Syrian hamster embryo cells, known to be immortalized and tumorigenic, had shorter TRFs than the original cells in primary culture did. These results indicate that hamster pancreatic duct carcinoma cells are immortalized, with the potential for proliferation ad infinitum, and provide a model for basic therapeutic research into the substances targeting telomerase.

Adenocarcinoma↗
PubMed1997

Microvascular changes associated with postischaemic hypoperfusion in rats.

The present study was undertaken to explore the cause of postischaemic hypoperfusion through morphological observations of the microstructure of brain cortex capillaries in rats with postischaemic hypoperfusion. Sixteen rats were used. The left middle cerebral artery of each animal was occluded for one hour (n = 8) or 2 hours (n = 8) and was followed by reperfusion for 2 hours. The regional cerebral blood flow (rCBF) of the ischaemia induced brain cortex was monitored continuously during the experiment and the microstructure of the brain cortex capillaries was then observed under electron microscope. Postischaemic hypoperfusion was observed in both ischaemia groups. The rCBF after (1.5 hours of reperfusion was significantly lower in the 2-hour ischaemia group than in the one-hour ischaemia group. The number of endothelial microvilli (MV) per capillary in the one-hour ischaemia group did not differ significantly from the control (the right cortex capillaries), whereas it was significantly higher in the 2-hour ischaemia group (p < 0.05). The ratio of the inner diameter to the outer diameter of capillaries decreased significantly in both ischaemia groups, and the ratio in the 2-hour ischaemia group was significantly lower than that in the one-hour ischaemia group (p < 0.05). Thus the present study statistically revealed that as postischaemic perfusion of the brains decreases, the number of MV increases, and endothelial cells swell more markedly. These microvascular changes seem to represent morphological factors associated with postischaemic hypoperfusion.

Animals↗
PubMed1997

Loss and apoptosis of smooth muscle cells in intracranial aneurysms. Studies with in situ DNA end labeling and antibody against single-stranded DNA.

Pathological specimens were collected from 14 unruptured and 13 ruptured aneurysms at the time of clipping and studied in order to assess the underlying mechanism of rupture by investigating degeneration of the aneurysmal wall and possible involvement of apoptosis. Immunohistochemistry with anti-actin antibody showed few smooth muscle cells in the ruptured aneurysms and replacement of the muscularis layer by a fibro-hyalin tissue. However, at least one layer of smooth muscle cells was clearly observed in the unruptured aneurysms. Thus, smooth muscle cells in the wall of the ruptured aneurysms were much more degenerated than those in the wall of unruptured aneurysms. In addition, unruptured aneurysms with an angiographically smooth wall showed well-layered positive staining for anti-smooth muscle actin antibody while those with irregular shapes rarely reacted. We found, for the first time, evidence of DNA fragmentation in the aneurysmal wall. Apoptotic bodies were detected by means of a terminal transferase (TdT)-mediated dUTP biotin nick end labelling technique (TUNEL) and an anti-single-stranded DNA antibody in 54% (7/13) of the ruptured aneurysms. In contrast, apoptotic bodies were found in only 7% (1/14) of the unruptured cases. These results suggest that apoptotic cell death might be involved in the rupture of aneurysms.

Actins↗
PubMed1997

Genomic alterations of human gliomas detected by restriction landmark genomic scanning.

Alterations of genomic DNA in eight primary astrocytic tumors and two glioma cell lines were examined using a recently developed two-dimensional gel electrophoresis method called restriction landmark genomic scanning (RLGS). RLGS allows us to detect amplifications, deletions, and methylation in genomic DNA in one procedure without requiring any polymorphic markers. Approximately 2000 spots (landmark sites) in tumor specimens were compared with those in normal brain tissue. The 10 spots with intensified signal were reproducibly detected in at least 50% of primary tumors, implying amplification of corresponding DNA sequences. Conversely, 12 spots with reduced signal were observed in more than 50% of all tumors, suggesting inactivation by allelic loss, homozygous deletion, or CpG island methylation. These results suggest that common genetic alterations are closely correlated with the genesis or progression of human gliomas.

Brain Neoplasms↗
PubMed1997

Acute subdural hematomas due to rupture of cortical arteries: a study of the points of rupture in 19 cases.

BACKGROUND: Several cases of acute subdural hematomas (ASDHs) due to rupture of cortical arteries are reported. They have several characteristic features: (1) their outcome is relatively good; (2) the cause is a trivial head injury; (3) patients are elderly; (4) a lucid interval is recognized; (5) hypertension is associated in many cases; and (6) cerebral contusion is absent. However, there has been no report about the points of rupture in the cortical arteries. METHODS: In 19 of the 125 patients with ASDHs admitted to our department, the cause of ASDH was bleeding from cortical arteries. The bleeding points were detected at surgery. Cases associated with cerebral contusion during or after the operation were excluded. In this article, we describe the clinical findings and the sites of bleeding from arteries in 19 cases of ASDH due to rupture of cortical arteries. RESULTS: The sites of ruptured arteries were as follows: prefrontal artery in one of 23 identified arteries (4.3%); precentral artery in five (21.7%); central artery in four (17.3%); anterior parietal artery in four (17.3%); angular artery in three (13.0%); middle temporal artery in four (17.3%); and posterior temporal artery in two arteries (8.7%). Two ruptured arteries in the same craniotomy were observed in four patients (17.3%). All points of rupture were located near the sylvian fissure (within 3 cm length around the sylvian fissure) and none in the base or vertex of the brain. CONCLUSION: If an ASDH occurs following a trivial head injury, rupture of cortical arteries should be considered as a possible cause. Wide craniotomy sufficiently covering the region surrounding the sylvian fissure should be performed to obtain hemostasis of bleeding points.

Acute Disease↗
PubMed1997

Rapid resolution of symptomatic acute subdural hematoma: case report.

BACKGROUND: Only a few cases showing spontaneous resolution of acute subdural hematoma (ASDH) have been reported. Several possible mechanisms of spontaneous resolution of ASDH have been reported. Two possible hypotheses have been suggested: (1) the hematoma is diluted by cerebrospinal fluid (CSF) due to tearing of the arachnoid membrane and is washed out, (2) the hematoma is compressed by the pressure produced by acute brain swelling and redistributed. In this article, we report a patient with a rapid spontaneous resolution of an ASDH and discuss the mechanisms. METHODS: We experienced a case of a spontaneous resolution of symptomatic ASDH within only 3 hours. Characteristic serial changes on computed tomography (CT) corresponding to neurologic changes were obtained. RESULTS: Serial CT findings showing changes corresponding to neurologic fluctuation were obtained. The characteristic features of the CT findings are as follows: (1) participation of CSF at the lateral portion of the hematoma was recognized during the early period after injury, (2) no cerebral contusion was identified, (3) acute cerebral swelling was not identified, (4) when the neurologic state deteriorated, the hematoma had not enlarged, but there was an increase in the low-density area corresponding to participation of the CSF and midline shift was recognized. CONCLUSION: Spontaneous resolution of ASDH depends on both dilution due to CSF participation and redistribution of the blood; but acute cerebral swelling is not a necessary condition. Elasticity of the brain and absence of cerebral contusion obstructing the outflow of the cerebrospinal fluid is optimal.

Acute Disease↗
PubMed1997

Analyses of human gliomas by restriction landmark genomic scanning.

The 16 primary gliomas were examined for changes in genomic DNA using a recently developed 2-dimensional gel electrophoresis method called restriction landmark genomic scanning (RLGS). This approach allows detection of DNA amplification, deletion, methylation and potentially other genetic rearrangements represented as decreases and increases in spot/fragment intensity on an autoradiogram. Approximately 2,000 landmark sites in tumor DNA were compared with those of DNA isolated from normal brain tissues. Seven spots showing intensified signal were consistently detected in at least 50% of tumors, implying activation of corresponding DNA sequences, and 8 additional spots having reduced signal were observed, again in more than 50% of all tumors, suggesting inactivation by the loss of 1 allele or homozygous deletion. Decreased signal may also infer relative CpG island methylation state. Of those spots consistently identified in tumors, 2 amplified and 4 reduced spots were found to be characteristic of low- and high-grade tumors, while the remaining 5 amplified and 4 reduced spots were associated with high-grade gliomas only, suggesting a link of specific mutations to degree of malignancy. A separate subset of glioblastomas evaluated, however, showed no alterations in these 'hot spots' which were detected in even low grade astrocytomas. The results demonstrate the genetic heterogeneity of glioblastoma and implicate the progression of neoplasia via differing genetic pathways.

Astrocytoma↗