Biomedical subjects

T Sakaki

Publications and source records attributed to T Sakaki.

At least 37 records · Page 2Linked to original sources

PubMed2001

Effect of carotid endarterectomy on chronic ocular ischemic syndrome due to internal carotid artery stenosis.

OBJECTIVE: We evaluated the effect of carotid endarterectomy on chronic ocular ischemic syndrome due to internal carotid artery stenosis by use of data obtained from ophthalmic artery color Doppler flow imaging. METHODS: We examined 11 patients with ocular ischemic syndrome due to internal carotid artery stenosis (>70% stenosis) who were being treated by carotid endarterectomy. Ophthalmic artery color Doppler flow imaging indicated ophthalmic artery flow direction and peak systolic flow velocity and was performed before and at 1 week, 1 month, and 3 months after surgery. RESULTS: We assessed the ophthalmic arteries of 11 patients via color Doppler flow imaging. Before undergoing carotid endarterectomy, five patients showed reversed ophthalmic artery flow. In the other six patients who experienced antegrade ophthalmic artery flow, the average peak systolic flow velocity was 0.09 +/- 0.05 m/s (mean +/- standard deviation). Preoperative reversed flow resolved in each patient 1 week after undergoing surgery. All patients showed antegrade ophthalmic artery flow. The average peak systolic flow velocity in the patients who had preoperative antegrade flow rose significantly, to 0.21 +/- 0.14 m/s (P < 0.05). There was no significant change as compared with findings at 1 week after surgery. During the follow-up period (mean, 32.4 mo), no patients complained of recurrent visual symptoms. At the end of the study period, visual acuity had improved in five patients and had not worsened in the other six patients. CONCLUSION: Carotid endarterectomy was effective for improving or preventing the progress of chronic ocular ischemia caused by internal carotid artery stenosis.

Angiography↗

PubMed2001

A scanning technique to measure regional cerebral blood flow and oxyhemoglobin level.

OBJECTIVE: The application of a laser scanning technique to measure regional cerebral blood flow (CBF) and tissue hemoglobin oxygenation (HbO2) using the rat closed cranial window preparation is described. METHODS: Twenty-nine male Wistar rats were used to consecutively measure local CBF by laser Doppler flowmetry and tissue HbO2 by a microspectrophotometric method at multiple corresponding cortical locations. The scanning technique used a computer-controlled micromanipulator. Data from three experimental models are presented: the whisker stimulation model, the ischemia-reperfusion model, and the sinus-vein thrombosis model. Sequential changes in local CBF and HbO2 data before, during, and after stimulation, ischemia, and sinus thrombosis were examined. Data from predefined locations within the same region were correlated with the topographical location and then arranged in a three-dimensional image. RESULTS: In the whisker stimulation model, we found a disproportionate increase in CBF (32 +/- 12%) as compared with that of HbO2 (9 +/- 4%) during stimulation. In the ischemia-reperfusion model, the three-dimensional image showed heterogeneous low CBF (depending on the area) and homogeneous HbO2 at a reduced level during ischemia and postischemic hyperperfusion. However, the range of oxygenation was normal after reperfusion. In the sinus-vein thrombosis model, drainage of the unsaturated blood via the collateral pathways was noted. CONCLUSION: The laser scanning technique is useful for visualizing sequential changes in hemodynamic-metabolic interactions of cortical brain tissue. This technique can reveal phenomena not detected by traditional monitoring procedures.

Animals↗

PubMed2001

Comparative study of 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin staining for quantification of early brain ischemic injury in cats.

There are no staining methods that can reliably and unequivocally detect final infarcts in the acute stage of experimental ischemia. In most instances, 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin and eosin (HE) stainings are accepted for this purpose, but neither is perfect. We performed a comparative study of the TTC immersion method and HE staining for quantification of early brain ischemic injury in cats, focussing on the reproducibility associated with planimetry. Focal brain ischemia was produced by middle cerebral artery (MCA) occlusion via the transorbital approach in 14 cats. After 6 h of occlusion, two slices of 3 mm thickness, passing through the optic chiasma and mammillary body, were selected for pathological examination. TTC immersion and HE staining were both used for planimetric study of the surface of the same slice. The area of the injury was traced manually with the aid of computerized digital planimetry and expressed as a percentage of the area of the contralateral hemisphere. The area of hemispheric injury and the area of gray matter injury were separately calculated in the TTC specimens, and each was compared with the area of gray matter injury in the HE-stained specimens. Measurements were repeated twice on each slice to estimate errors associated with manual tracing of the boundary of the area of injury. The mean percentage values of the area of injury in the TTC-immersed gray matter specimens were lower than those detected by HE staining, although there was a very significant correlation between the two. The differences between each two measurements of TTC-determined gray matter injury were significantly less than those between each two measurements of HE-determined gray matter injury. The differences between each two measurements of TTC-determined hemispheric injury were slightly less than those between each two measurements of TTC-determined gray matter injury, although there was no significant difference between them. For quantifying ischemic injury after 6 h of MCA occlusion in cats, the TTC immersion method is more reproducible and simpler in manner than HE staining, but the results of both are significantly correlated.

Animals↗

PubMed2001

Intermittent isometric exposure prevents brain retraction injury under venous circulatory impairment.

It is recognized that surgical obliteration of the cerebral veins by additional brain compression using retractors is dangerous. However, there is a lack of satisfactory management of this problem. We investigated whether intermittent brain compression can reduce brain injury from cerebral venous circulation disturbances (CVCDs). In Wistar rats (n = 25), a solitary cortical vein was occluded photochemically. The brain surface was compressed by a spring balance and constant compression at 30 mmHg was carried out for 60 min. Intermittent procedure compression protocols included four 15 min compressions at 5 min intervals, intermittent isometric exposure (IM), and intermittent isotonic exposure (IT). Local cerebral blood flow (ICBF) in the compressed area was measured together by laser-Doppler (LD) with the degree of brain compression. After 24 h, the brains were examined histologically. The animals were divided into the following five groups (each n = 5): 1, a sham operated control; 2, cortical vein occlusion (VO); 3, VO + continuous brain compression (CC); 4, VO + IM; and 5, VO + IT. The ICBF decreased significantly during the compression; however, recovery after the series of compressions was observed only in the VO + IM group, not in the VO + CC and the VO + IT groups (p < 0.05). The depth of the brain surface increased stepwise in the VO + IT group compared with the VO + IM group (p < 0.01). The resulting tissue damage was significantly larger in the VO + CC and VO + IT groups than in the vein occlusion group (p < 0.05), but not in the VO + IM group. The results of the present study suggest that intermittent isometric exposure under CVCDs could decrease brain retraction injury during neurosurgical operations and be more beneficial than continuous compression, providing that the compression pressure declines as the process advances.

Animals↗

PubMed2001

Cerebral blood flow and tissue oxygen saturation in immediate and progressive ischemia in rat brain.

The aim of the present study was to investigate whether immediate ischemia is more harmful to the brain than progressive ischemia. To do so, we examined the correlation between the degree and the process of ischemia using hypobaric hypotension technique, which was used to reduce systemic blood pressure acutely or progressively below the lower threshold of CBF regulation, in rat brain. In Wistar rats (n = 21), global ischemia using bilateral carotid arteries occlusion coupled with hypobaric hypotension was induced by lowering mean arterial blood pressure (MABP) progressively to 55, 45 and 35 mmHg or immediately to 35 mm Hg. Local cerebral blood flow (ICBF) by laser Doppler (LD) flowmetry and tissue hemoglobin oxygen saturation (HbSO2) by a microspectrophotometric method were measured at 25 corresponding locations using a 'scanning' technique which employs a computer-controlled micromanipulator. Regional CBF (rCBF) and rHbSO2 were determined by calculation of the median value from the 25 ICBF and IHbSO2 data. In the 'progressive' group, rCBF and rHbSO2 decreased gradually and reached 12.2 +/- 15.8 LD-units and 44.9% +/- 13.4% at 35 mm Hg of MABP, respectively. In the 'immediate' group, both parameters dropped suddenly to 7.86 +/- 10.6 LD-units (p < 0.01 vs. CBF of the progressive group) and 22.5% +/- 15.5% (p < 0.001 vs. tissue HbSO2 of the progressive group) from the control at 35 mmHg. These data suggested that cerebral ischemia is better tolerated if it is induced gradually. CBF recorded by LD-scanning technique and HbSO2 value by microspectrophotometric method correlated well in the ischemic condition, indicating that HbSO2 can be preserved if CBF is decreased gradually.

Animals↗

PubMed2001

Implantation of xenografts into the parkinsonian rat brain after portal venous administration of xenogeneic donor spleen cells.

OBJECT: The purpose of the present study was to examine the effect of pretransplantation portal venous immunization with ultraviolet B (UVB)-treated donor spleen cells on neural xenograft transplantation. METHODS: Cells from a murine catecholaminergic cell line derived from the B6/D2 F1 mouse, CATH.a, were used as a xenograft. Thirty hemiparkinsonian rats were divided into three different treatment groups. Group 1 received saline in the dopamine-denervated striatum; Group 2 received xenograft cells; and Group 3 received portal venous administration of UVB-irradiated B6/D2 F1 splenocytes 7 days before receiving xenograft cells. Xenograft function was determined by reviewing apomorphine-induced rotation at 2-week intervals, and xenograft survival was examined at 4 and 12 weeks after transplantation by immunohistochemical staining for murine tyrosine hydroxylase (THase). Rotational behavior was improved in both xenograft-transplanted groups (Groups 2 and 3); however, the animals in Group 3 displayed a significantly reduced rotational behavior compared with Group 2. In Group 2, many inflammatory cells and a few THase-positive cells were found at the graft sites 4 weeks after transplantation. In Group 3, however, a large number of THase-positive cells were found with few inflammatory cells. The THase-positive cells disappeared in the Group 2 rats at 12 weeks, but remained in Group 3 animals. In Group 3 rats proliferation of spleen cells in a mixed lymphocyte reaction was suppressed in a donor-specific fashion. CONCLUSIONS: This work demonstrates improved neural xenograft survival and function by pretransplantation portal venous immunization with UVB-irradiated xenogeneic donor splenocytes. On the basis of these findings, the authors suggest the possibility of creating donor-specific immunological tolerance in the brain by administration of xenogeneic donor lymphocytes via the portal vein.

Animals↗

PubMed2001

Peripheral ophthalmic artery aneurysm. Report of two cases.

The authors report on two patients with peripheral ophthalmic artery (OphA) aneurysms and demonstrate the mechanism by which these lesions are formed by using OphA color Doppler flow velocimetry imaging. During formation of these two aneurysms, the hemodynamic stress on the OphA was quite significant.

Adult↗

PubMed2001

Possible control of intermittent cerebral ischemia by monitoring of direct-current potentials.

OBJECT: Neurosurgically induced temporary occlusion of intracranial arteries carries the risk of cerebral ischemic damage. Because negative shifts in the cortical direct-current (DC) potential indicate tissue depolarization and, thus, critical ischemic stress, the authors hypothesized that recordings of these potentials could help to determine the optimal duration and frequency of induced intermittent focal ischemia to prevent brain injury. The investigators related the results of DC recordings both to simultaneously recorded decreases in extracellular Ca++ concentration ([Ca++]o), which reflect Ca++ entry into cells, and to histological outcome. METHODS: In cats anesthetized with halothane the effects of intermittent brief (10 minutes long, six times [6 x 10-min group]) and prolonged (20 minutes long, three times [3 x 20-min group]) episodes of middle cerebral artery occlusions were compared with those of a single continuous episode (1 x 60-min group). Laser Doppler flow probes and ion-selective microelectrodes were used to measure cerebral blood flow, DC potentials, and [Ca++]o in cortical tissues of ectosylvian gyri. Negative shifts in DC potential were evaluated in the three groups during the entire 60-minute-long period of ischemia and were smallest in the 6 x 10-min group, larger in the 3 x 20-min group, and largest in the 1 x 60-min group. Accordingly, infarct volumes were smallest in the 6 x 10-min group, intermediate in the 3 x 20-min group, and largest in the 1 x 60-min group. Decreases in ischemic [Ca++]o were significantly greater in the 1 x 60-min group than in the two groups in which there were repetitive occlusions, and recovery of [Ca++]o after reperfusion normalized only in the 1 x 60-min group. CONCLUSIONS: The DC potential may provide a reliable measure to optimize intermittent ischemia and to achieve minimal ischemic brain injury during temporary neurosurgical occlusion of cerebral arteries.

Animals↗

PubMed2001

Radiosurgery-induced brain tumor. Case report.

The authors describe a case of glioblastoma multiforme (GBM) associated with previous gamma knife radiosurgery for a cerebral arteriovenous malformation (AVM). A 14-year-old boy had undergone radiosurgery for an AVM, which was performed using a 201-source 60Co gamma knife system at another institution. The maximum and margin radiation doses used in the procedure were 40 and 20 Gy, respectively. One year after radiosurgery, the patient noticed onset of mild left hemiparesis due to radiation necrosis. Six and one-half years after radiosurgery, at the age of 20 years, the patient experienced an attack of generalized tonic-clonic seizure. Magnetic resonance (MR) imaging revealed the existence of a brain tumor in the right parietal lobe. The patient underwent an operation and the histological diagnosis of the lesion was GBM. Ten months following the operation, that is, 99 months postradiosurgery, this patient died. To the best of the authors' knowledge, this is the first reported case of a neoplasm induced by radiosurgery for an AVM and the second case in which it occurred following radiosurgery for intracranial disease.

Brain Neoplasms↗

PubMed2001

[Surgery for intractable epilepsy in children: pre- and perioperative evaluations with special reference to dipole tracing method estimated from interictal spike].

Methods of preoperative and perioperative evaluation methods for surgical treatment of intractable epilepsy in children are described. Among non-invasive diagnostic methods, EEG-video monitoring is the most fundamental. Amygdalohippocampal volume measurement by MR was useful for the differential diagnosis of mesial temporal lobe epilepsy (TLE) from lateral TLE and generalized epilepsy. The dipole tracing method with a realistic head model was useful for identification of epileptic foci from the interictal spikes of scalp EEG, when an abnormal electric source was estimated as an equivalent current dipole (ECD) in the brain of patients with organic lesion and TLE. ECD concentration ratio ranged from 70 to 90% within 20 mm around the lesion. After lesionectomy seizures disappeared in every patient. The mean distance between the centers of the ECD and epileptic focus (identified by subdural electrode recording) was 14 mm (range: 8 to 18 mm). ECDs of mesial TLE were located in the temporal base rather than mesial temporal lobe, whereas those of lateral TLE in the lateral cortex precisely. In unilateral, intermediate and bilateral TLE, 76%, 52% and 36% of ECDs were localized in the ictal onset zone respectively (p = 0.007). Electrical cortical stimulation with chronically placed intracranial electrodes was used to accurately identify eloquent areas to avoid postsurgical complications. Immediately after operation, 10 to 20% of patients showed better or deteriorated results in neuropsychological examinations, which recovered in all patients after one year. Postoperative seizures were absent in three fourths of patients. Further efforts are needed to obtain better seizure control in future.

Adolescent↗

PubMed2001

[Microcirculatory changes in the development of the cerebrovascular adaptation].

Recently, long-term cerebrovascular adaptations after unilateral carotid ligation that increase the tolerance of the brain to subsequent episode of ischemia was reported(J Cereb Blood Flow Metab, 1998). However, the pathophysiological mechanisms underlying the phenomenon was unknown. We examined regional cerebral blood flow(rCBF) before, during and after subsequent ischemia in the development of the adaptation. Male Wistar rats(n = 18) were used. Unilateral(right) carotid artery ligation was performed 3 hours(group A: n = 8), 3 days(group B: n = 10) before forebrain ischemia. With bilateral carotid arteries occlusion, mean arterial blood pressure(MABP) was reduced by hypobaric hypotension down to 50 mmHg and maintained constant for 30 min. After hypotension, the experiment continued for 90 min. Local CBF were registered at 25(5 x 5) identical locations by laser Doppler scanning in the cortex during the experiment in bilateral hemispheres(at control phase, after the left carotid artery ligation, during ischemia and after hypotension). The physiological variable such as blood pressure and gas analysis were within normal range in all groups. There were no differences of rCBF between the right and left hemispheres in group A during the experiment. In group A, rCBF of both hemispheres significantly decreased after the ligation of the left carotid artery, during the induced ischemia (P < 0.05), and recovered to the value of before ischemia. Whereas, in group B rCBF of the left side(non-occluded side) decreased after the ligation of the left carotid artery, during the induced ischemia(P < 0.05), and recovered to the value of before ischemia, but rCBF of the right side(occluded side) decreased only during the induced ischemia(P < 0.05) and rCBF of the right side was significantly higher than the left brain after ligation of the carotid artery, during ischemia and after hypotension(P < 0.05). On the basis of these data, we concluded that cerebrovascular adaptations can be acquired by 3 days after unilateral carotid artery occlusion and the tolerance phenomenon is certainly attributed to microcirculatory improvement.

Animals↗

PubMed2001

[Neuroprotective effect of a neurotoxin, 3-nitropropionic acid, against hypoxic damage to the gerbil hippocampus: neuroprotection after the onset of hypoxic depolarization].

Ischemic/hypoxic tolerance induced by a subtoxic dose of neurotoxin, 3-nitropropionic acid(3-NPA), was recently reported as "chemical preconditioning". We previously showed that the neuroprotective effect by chemical preconditioning with 3-NPA was induced by prolonging the delay to hypoxic depolarization (HD) via activating adenosine receptors. In this study, we electrophysiologically assessed whether the protective effect of chemical preconditioning was potent after the onset of HD. An in vitro hippocampal slice model from adult gerbils was used to study the delay to HD during hypoxia and the recovery of synaptic responses after hypoxia. Hypoxia was sustained until a fixed period(8 min) following HD. These responses were examined in control slices and slices pretreated with subtoxic dose of 3-NPA(4 mg/kg) intraperitoneally at 3 hours prior to slice preparation. The delay to hypoxic depolarization in 3-NPA treated slices was significantly prolonged(p < 0.05). The field excitatory postsynaptic potential recovery after a fixed period of hypoxia under HD was also significantly improved in the 3-NPA treated group(48.6 +/- 23.8%) compared with the control group(29.2 +/- 12.2%) (p < 0.05). This finding indicates that chemical preconditioning with 3-NPA induces the neuroprotective effect against hypoxic damage after as well as before the onset of HD to the hippocampus.

Animals↗

PubMed2001

Quantitative kinetics of [124I]FIAU in cat and man.

UNLABELLED: For the assessment of the efficacy of clinical gene therapy trials, different imaging modalities have been developed that enable a noninvasive assessment of location, magnitude, and duration of transduced gene expression in vivo. These imaging methods rely on a combination of an appropriate marker gene and a radiolabeled or paramagnetic marker substrate that can be detected by PET or MRI. Here, we assess whether the nucleoside analog 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyl-5-iodouracil (FIAU), a specific marker substrate for herpes simplex virus type 1 thymidine kinase (HSV-1-tk) gene expression, penetrates the blood-brain barrier (BBB) as an essential prerequisite for a noninvasive assessment of HSV-1-tk gene expression in gliomas. METHODS: No-carrier-added [(124)I]FIAU was synthesized by reacting the precursor 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyluracil (FAU) with carrier-free [(124)I]NaI. The course of biodistribution of [(124)I]FIAU was investigated in anesthetized cats (n = 3; organs) and in one patient with a recurrent glioblastoma (plasma and brain) by PET imaging over several hours (cats, 1-22 h) to several days (patient, 1-68 h). FIAU PET was performed in conjunction with multitracer PET imaging (cerebral blood flow and cerebral metabolic rate of O(2) in cats only; cerebral metabolic rate of glucose and [(11)C]methionine in all subjects). A region-of-interest analysis was performed on the basis of coregistered high-resolution MR images. The average radioactivity concentration was determined, decay corrected, and recalculated as percentage injected dose per gram of tissue (%ID/g) or as standardized uptake values (SUVs). RESULTS: The average chemical yield of [(124)I]FIAU synthesis was 54.6% +/- 6.8%. The chemical and radiochemical purities of [(124)I]FIAU were found to be >98% and >95%, respectively. In cats, the kinetic analysis of [(124)I]FIAU-derived radioactivity showed an early peak (1-2 min after injection) in heart and kidneys (0.20 %ID/g; SUV, 4.0) followed by a second peak (10-20 min after injection) in liver and spleen (0.16 %ID/g; SUV, 3.2) with subsequent clearance from tissues and a late peak in the bladder (10-15 h after injection). In the unlesioned cat brain, no substantial [(124)I]FIAU uptake occurred throughout the measurement (<0.02 %ID/g; SUV, <0.4). In the patient, [(124)I]FIAU uptake in normal brain was also very low (<0.0002 %ID/g; SUV, <0.16). In contrast, the recurrent glioblastoma revealed relatively high levels of [(124)I]FIAU-derived radioactivity (5-10 min after injection; 0.001 %ID/g; SUV, 0.8), which cleared slowly over the 68-h imaging period. CONCLUSION: The PET marker substrate FIAU does not penetrate the intact BBB significantly and, hence, is not the marker substrate of choice for the noninvasive localization of HSV-1-tk gene expression in the central nervous system under conditions in which the BBB is likely to be intact. However, substantial levels of [(124)I]FIAU-derived radioactivity may occur within areas of BBB disruption (e.g., glioblastoma), which is an essential prerequisite for imaging clinically relevant levels of HSV-1-tk gene expression in brain tumors after gene therapy by FIAU PET. For this purpose, washout of nonspecific radioactivity should be allowed for several days.

Animals↗

PubMed2001

[The effect of C 1 esterase inhibitor on ischemia: reperfusion injury in the rat brain].

BACKGROUND: Despite the current interest in thrombolytic therapy for acute stroke, ischemia-reperfusion injury remains a potentially hazardous complication. The complement system is thought to play a major role in initiating some of the inflammatory events occurring in the reperfusion injury. This study was conducted to explore the effect of C 1 esterase inhibitor (C 1 INH) on the reperfusion injury in rat middle cerebral artery (MCA) occlusion-reperfusion model. METHODS: Twenty-nine male Wistar rats were used. Intraluminal MCA occlusion was performed for 60 minutes. Just before the reperfusion, C 1 INH(50 IU/kg, C 1 INH group, n = 15) or saline (control group, n = 14) was administrated. Forty-eight hours after the reperfusion, infarct volume and myeloperoxidase(MPO) activity of the brain were evaluated. RESULT: Infarct volume and MPO activity were significantly smaller in the C 1 INH group(86.5 +/- 76.8 mm3, 0.38 +/- 0.30 U/g) than in control group(179 +/- 92.8 mm3, 1.37 +/- 0.46 U/g) (p < 0.01). CONCLUSION: The results of this study provided the first evidence that C 1 INH reduced polymorphonuclear leukocytes(PMN) accumulation and reperfusion damage in the brain.

Animals↗

PubMed2001

[A case of glioblastoma associated with dissemination, secondary to intratumoral hemorrhage].

The occasional occurrence of dissemination and tumor-associated hemorrhage from glioblastoma is well known and widely reported in the literature. The authors present a case of cerebral glioblastoma with dissemination possibly caused by intratumoral hemorrhage. Computed tomographic (CT) scan revealed a small hemorrhagic lesion in the right frontal lobe and a sylvian fissure in a 62-year-old man who complained of sudden headache. Four months later, he again presented with neck pain followed by weakness and numbness in the extremities. Magnetic resonance images (MRI) of the cervical spine demonstrated multiple enhanced tumors. After transfer to our institution, a large cystic tumor with ring-like enhancement was found in the right frontal lobe. Progressive neurological deficits prompted an operation on the cervical tumors and a pathological diagnosis of anaplastic astrocytoma with a negative reaction for glial fibrillary acidic protein (GFAP) was made. Intraoperative findings of the second operation for the cerebral tumor disclosed that the tumor extended outside the frontal lobe, growing substantially within the sylvian subarachnoid space and involving middle cerebral artery branches. The results of a pathological study were those consistent with glioblastoma having tumor cells with little positive reaction to GFAP staining. Craniospinal radiation was undertaken as a palliative treatment of the residual tumor. On MRI, multiple nodular dissemination in the lumbo-sacral region was diagnosed. Two months later, the patient suddenly lost consciousness and suffered eye deviation. A CT scan found a large tumor-associated hemorrhage in the right frontal lobe. Emergency evacuation of the hematoma with gross total removal of the residual tumor was performed. He temporarily returned to his preoperative neurological condition but died later due to the recurrent cervical tumor. Dissemination secondary to intratumoral hemorrhage in patients with glioblastoma has not been reported. This rare case shows that hemorrhagic glioblastoma is at risk for dissemination, especially when the hemorrhage occurs in or near the subarachnoid space and tumor cells have a less positive reaction for GFAP staining.

Brain Neoplasms↗

PubMed2001

[A case of spontaneous subarachnoid hematoma of the high cervical spine presenting as Brown-Séquard's syndrome].

Spinal subarachnoid hematoma is a very rare event, occurring exclusively in the thoracic or lumbar region. We report the first recorded case of spontaneous subarachnoid hematoma in the high cervical spine presenting as Brown-Séquard's syndrome. A 57-year-old woman with no prior problems suddenly presented with Brown-Séquard's syndrome at the C1-2 disc space level following occiput neck pain. Her consciousness was clear and urinary retention was not observed. Lumbar puncture revealed no evidence of hemorrhage. Neuroradiological evaluation, including myelography, CT myelography, and MRI, demonstrated a defined hematoma in the cervical subarachnoid space at the C1-2 level. Angiographical study yielded negative findings. The patient's neurological state remained unchanged for the following 6 days. On the 7th day from the onset, a C1 and C2 laminectomy was performed. A defined clot was found after incising the intact dura matter and arachnoid membrane. This clot was easily aspirated except for a small part which was found attached to a pial vessel on the dorsal surface of the spinal cord. No underlying pathology other than coagulated blood was confirmed. Three months postoperatively, she had no neurological deficits. The clinical course of spontaneous spinal subarachnoid hematoma varies according to the rapidity and severity of hematoma formation. An immediate and precise diagnosis using multimodal neuroimagings is vital because decompressive surgery can dramatically ameliorate the neurological sequelae.

Brown-Sequard Syndrome↗

PubMed2001

[Experimental study of pharmacological hypothermia: enhanced neuroprotective effect of a novel 5-HT 1 A agonist SUN N4057 by the pharmacological hypothermia].

PURPOSE: 5-hydroxytryptamine(5-HT) 1 A receptor agonists have a potentially marked neuroprotective reaction by both neuroprotective and hypothermic effects. We previously reported (1) the neuroprotective effect against the cerebral ischemia under normothermic condition, and (2) the hypothermic effect of the novel compound of 5-HT 1 A agonist, SUN N4057. The present investigation was designed to examine the enhancement of the neuroprotective effect by its pharmacological hypothermia. METHODS: In 24 anesthetized cats(body weight 1.9-4.6 kg), the left middle cerebral artery(MCA) occlusion was performed via the transorbital approach. Just after MCA occlusion, SUN N4057(6 micrograms/kg/min) was infused. Physiological parameters were measured continuously, and arterial blood gas was analyzed hourly for 6 hours and maintained within the normal ranges. Animals were randomly allocated to the following three groups: (1) ischemic controls infused with sterile saline(Group A, n = 8), (2) SUN N4057 under normothermic condition(Group B, n = 8), (3) SUN N4057 (Group C, n = 8). Then, brain coronal sections of 3 mm in thickness were stained with 1% triphenyltetrazolium chloride(TTC) solution, and hemispheric infarct volumes were calculated by using a computerized image analysis system. RESULTS: There were no significant differences in any physiological parameters among 3 groups. In Group C, brain temperature decreased significantly starting 1 hour after MCA occlusion and dropped by 2.1 +/- 0.7 degrees C 5 hours. Infarct volumes were 35.6 +/- 6.9% (Group A), 23.3 +/- 5.8% (Group B) and 12.3 +/- 11.3% (Group C), respectively. There were significant differences among three groups(p < 0.05). CONCLUSION: On the basis of these data, we conclude that SUN N4057 provides more effective neuroprotection by the combination of hypothermic and neuroprotective effects. Chemical hypothermia may lead to a new therapeutic approaches for treatment of brain ischemia.

Animals↗

PubMed2000

Coexpression of genetically engineered fused enzyme between yeast NADPH-P450 reductase and human cytochrome P450 3A4 and human cytochrome b5 in yeast.

Human hepatic cytochrome P450 3A4 (CYP3A4) was expressed in yeast Saccharomyces cerevisiae. While the expression level was high as compared with other human hepatic cytochrome P450s, CYP3A4 showed almost no catalytic activity toward testosterone. Coexpression of CYP3A4 with yeast NADPH-P450 reductase did not give a full activity. Low monooxygenase activity of CYP3A4 was attributed to the insufficient reduction of heme iron of CYP3A4 by NADPH-P450 reductase. To enhance the efficiency of electron transfer from NADPH-P450 reductase to CYP3A4, a fused enzyme was constructed between CYP3A4 and yeast NADPH-P450 reductase. The rapid reduction of the heme iron of the fused enzyme by NADPH was observed. The fused enzyme showed a high testosterone 6beta-hydroxylation activity with a sigmoidal velocity saturation curve. However, the coupling efficiency between NADPH utilization and testosterone 6beta-hydroxylation was only 10%. Finally, coexpression of the fused enzyme and human cytochrome b5 was examined. A significant decrease in the Km value and a remarkable increase in the coupling efficiency were observed. Substrate-induced spectra revealed that the dissociation constant of the fused enzyme for testosterone significantly decreased with coexpression of human cytochrome b5. These results strongly suggest that human cytochrome b5 directly interacts with the CYP3A4 domain of the fused enzyme and modifies the tertiary structure of substrate binding pocket, resulting in tight binding of the substrate and high coupling efficiency.

Base Sequence↗