Biomedical subjects

Kikuo Ohno

Publications and source records attributed to Kikuo Ohno.

28 records · Page 2Linked to original sources

PubMed2003

PET imaging of adenosine A(1) receptors with (11)C-MPDX as an indicator of severe cerebral ischemic insult.

UNLABELLED: We examined whether measurement of the adenosine A(1) receptor (A1-R) with PET can predict the severity of ischemic brain damage using an occlusion and reperfusion model of the cat middle cerebral artery (MCA) and [1-methyl-(11)C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX), a positron-emitting radioligand developed at our institution. METHODS: Eighteen adult cats underwent PET measurement of cerebral blood flow (CBF), A1-R, central benzodiazepine receptor (BDZ-R), and glucose metabolism with (15)O-labeled water, MPDX, (11)C-flumazenil (FMZ), and (18)F-FDG, respectively. The right MCAs of 13 cats were transiently occluded via a transorbital approach with microvascular clips. CBF was measured before occlusion of MCA, during occlusion, and immediately after reperfusion. After CBF measurement, A1-R, BDZ-R, and (18)F-FDG uptake were serially measured in the order listed. Two months later, the degree of ischemic damage was evaluated by T2-weighted MR images obtained with an animal MRI system and by analysis of histologic specimens. Five cats that received no operations were used as controls. RESULTS: The cats that underwent occlusion were divided into 3 groups: cats that did not survive the first day because of severe neurologic and systemic conditions (n = 4), cats that survived and had infarcted lesions in both the cortex and the striatum (n = 3), and cats that survived and had infarcted lesions only in the striatum (n = 6). CBF during occlusion of the MCA was significantly lower in all 3 ischemic groups than in the control group, but there was no significant difference among the ischemic groups. Right-to-left ratios of CBF and (18)F-FDG uptake did not significantly differ among the groups. MPDX binding and FMZ binding were significantly lower in the groups with severe ischemic insult than in the groups with little to no insult. CONCLUSION: The degree of decreased MPDX binding to A1-Rs after reperfusion was a sensitive predictor of severe ischemic insult. MPDX PET has good potential to become a suitable in vivo imaging technique for evaluating the function of adenosine and A1-Rs in relation to cerebral ischemia.

Animals↗

PubMed2002

Role of Ca(v) 2.3 (alpha1E ) Ca2+ channel in ischemic neuronal injury.

We investigated the role of the Ca(v)2.3 (alpha1E) channel in ischemic neuronal injury using Ca(v)2.3 mutant mice. In focal ischemia model with a complete occlusion of the middle cerebral artery in vivo, infarct at 24 h was significantly larger in Ca(v)2.3 mutant mice compared with that in wild-type controls. In vitro Ca2+ imaging studies using hippocampal slices revealed that oxygen-glucose deprivation induced a [Ca2+]i increase in the hippocampal CA1 region more vigorously in Ca(v)2.3 mutant mice than in wild-type controls, and that tetrodotoxin or bicuculline application abolished the difference between the genotypes. These results suggest that the Ca(v)2.3 channel plays a protective role in ischemic neuronal injury by a mechanism in which GABAergic neuronal actions are involved.

Animals↗

PubMed2002

Intraoperative intrinsic optical imaging of neuronal activity from subdivisions of the human primary somatosensory cortex.

We performed intrinsic optical imaging of neuronal activity induced by peripheral stimulation from the human primary somatosensory cortex during brain tumor surgery for 11 patients. After craniotomy and dura reflection, the cortical surface was illuminated with a xenon light through an operating microscope. The reflected light passed through a bandpass filter, and we acquired functional images using an intrinsic optical imaging system. Electrical stimulation of the median nerve, or the first and fifth digits, induced biphasic intrinsic optical signals which consisted of a decrease in light reflectance followed by an increase. The decrease in light reflectance was imaged, and we identified a neural response area within the crown of the postcentral gyrus. In experiments on first and fifth digit stimulation, we identified optical responses in separated areas within the crown of the postcentral gyrus, i.e. near the central sulcus and near the postcentral sulcus. In the former response area, separate representations of the two fingers were observed, whereas in the latter response area, the two fingers were represented in the same region. A similar somatotopic representation was observed with electrical stimulation of the first and third branches of the trigeminal nerve. These results seem to support the hypothesis of hierarchical organization in the human primary somatosensory cortex.

Adult↗

PubMed2002

Inhibitory effect of activated protein C on cerebral vasospasm after subarachnoid hemorrhage in the rabbit.

This study investigated whether activated protein C (APC) improves the cerebral vasospasm in an experimental subarachnoid hemorrhage that was produced by the intracisternal injection of autologous blood. Male rabbits were divided into the following four groups: APC 0.1-and 0.5-mg groups, in which 0.1 and 0.5 mg APC were injected into the cisterna magna, respectively; a placebo group, in which saline was injected instead of APC; and a sham operation group that did not get injections of autologous blood, APC, and saline. On day 2, amount of clot in the basal cistern was significantly (p < 0.01) decreased in the APC 0.5-mg group. Percent diameter of the basilar artery on day 2 to that before injecting the blood was angiographically determined as 97.1 +/- 3.8% in the APC 0.5-mg group, which was significantly (p < 0.001) greater than the corresponding value in the placebo group (74.8 +/- 3.4%). The impaired endothelium-dependent relaxation following subarachnoid hemorrhage was normalized in the APC 0.5-mg group (p < 0.0001). These results suggest that APC would improve cerebral vasospasm following subarachnoid hemorrhage, possibly by decreasing the amount of subarachnoid clot and normalizing the impaired nitric oxide production/release.

Animals↗

PubMed2002

Preoperative evaluation of neurovascular compression in patients with trigeminal neuralgia by use of three-dimensional reconstruction from two types of high-resolution magnetic resonance imaging.

OBJECTIVE: To assess the value of three-dimensional (3-D) images reconstructed from 3-D constructive interference in steady state (3-D-CISS) and 3-D fast inflow with steady-state precession (3-D-FISP) images for the visualization of neurovascular compression in patients with trigeminal neuralgia. METHODS: Twenty-four consecutive patients with trigeminal neuralgia underwent preoperative 3-D-FISP and 3-D-CISS imaging. 3-D reconstruction of nerves and vessels was performed with the use of a volume-rendering method. We compared the 3-D reconstructed images with intraoperative findings. RESULTS: 3-D-CISS and 3-D-FISP images scanned from the same position clearly delineated the trigeminal nerve and vessels. 3-D reconstructed images showed the spatial relationship between the trigeminal nerve and causative vessels. The responsible arteries were identified from the 3-D reconstructed images, which closely simulated the microscopic operative view. CONCLUSION: 3-D reconstructions from two types of high-resolution magnetic resonance images (3-D-CISS and 3-D-FISP) are very useful for creating preoperative simulations and in deciding whether to perform surgery in patients with trigeminal neuralgia.

Adult↗

PubMed2002

Spontaneous intracerebral hematomas expanding during the early stages of hemorrhage without rebleeding. Report of three cases.

Expansion of intracerebral hematoma usually occurs in the chronic phase because of repeated bleeding from pre-existing vascular anomalies or exudation of blood from capillaries of the capsule. In contrast, spontaneous intracerebral hematoma expanding during the acute phase of hemorrhage without rebleeding is seldom seen. Three such cases are reported, along with magnetic resonance (MR) and computerized tomography (CT) follow-up studies. The follow-up MR images and CT scans demonstrated no evidence of rebleeding, but revealed gradual expansion of a fluid component of the hematoma, beginning in the acute phase. Volume alterations posthemorrhage are carefully documented. There was a characteristic phenomenon of layering, with the red blood cell component of the clot settling by gravity and the serum separating as well as seen in a test tube, depending on whether a preservative was used. Examination of blood samples indicated a possible correlation between expansion of the hematoma and the activities of both the fibrinolytic system and coagulation factors.

Acute Disease↗

PubMed2002

[Benign intracranial hypertension resulting from corticosteroid withdrawal: case report].

We report a case of benign intracranial hypertension (BIH) resulting from corticosteroid withdrawal. A 36-year-old woman was admitted to hospital because of an intractable headache. A neurological examination on admission showed no abnormalities other than a headache and nausea. CT, MRI, and angiogram examinations showed no abnormalities. Hematological and laboratory data were also normal. Continuous monitoring of her cerebrospinal fluid (CSF) pressure showed a value of over 25 mmHg during sleep, but papilledema was not observed. A diagnosis of BIH was made, with corticosteroid withdrawal considered to be the most probable cause. The patient was given isosorbide solution for 3 months. However, her clinical condition continued to deteriorate; she eventually began to develop visual loss, photopsia, and memory disturbances. She underwent lumboperitoneal shunt surgery, which immediately eliminated the headache, photopsia, and memory disturbances. She regained her vision over a five-month period. BIH should be considered as a differential diagnosis when an intractable headache develops after corticosteroid withdrawal, especially in young women.

Adult↗

PubMed2002

Reduced transduction efficiency of adenoviral vectors expressing human p53 gene by repeated transduction into glioma cells in vitro.

PURPOSE: Recombinant adenoviral vectors are widely used in clinical and experimental studies to treat malignant tumors. Recently, host immune responses have been proposed as a major limitation in using adenoviral vectors for repeated gene delivery. We demonstrate another limitation unrelated to host immunity. EXPERIMENTAL DESIGN: We repeatedly transduced an adenoviral vector expressing the human p53 gene (AxCIhp53) into U373MG, a p53-susceptible cell line, and established the AxCIhp53-resistant cell line U373R. Most U373R cells survived even after AxCIhp53 treatment due to reduced transduction efficiency. Expression levels of adenovirus receptors were estimated to investigate the cause of reduced transduction efficiency. The mutant vector was used to overcome the resistance. RESULTS: The transduction efficiency of an adenoviral vector possessing the reporter LacZ gene (AxCAZ2-F/wt) for U373R cells was 25.4-fold less than that for parent cells. The expression levels of integrins alpha(v)beta(3) and alpha(v)beta(5) were found to be decreased in U373R cells without affecting the expression levels of Coxsackievirus and adenovirus receptor. The mutant vector AxCAZ2-F/K20, with a linker and a stretch of 20 lysine residues at the COOH-terminal of the fiber protein, improved the transduction efficiency of U373R cells to 12.6-fold of that of AxCAZ2-F/wt. A mutant vector carrying the p53 gene, AxCAhp53-F/K20, dramatically induced apoptosis in U373R cells. CONCLUSIONS: Glioma cells expressing low levels of adenovirus receptors might survive and proliferate to recur after repeated adenoviral transduction, even if the adenoviral transduction is effective at first. Changing the tropism of vectors is a potent method to overcome resistance.

Adenoviridae↗

PubMed2002

Increased levels of tissue endostatin in human malignant gliomas.

PURPOSE: Malignant gliomas are typically angiogenic and express greater amounts of angiogenic factors. We examined glioma tissues for their expression of an endogenous inhibitor of angiogenesis, endostatin, a COOH-terminal fragment of collagen XVIII. EXPERIMENTAL DESIGN: We examined frozen tissues from 51 patients with astrocytic tumors (grade 2, 13; grade 3, 9; and grade 4, 29). Frozen tissues were subjected to immunoblot analysis and immunohistochemistry for endostatin. Tumor vascular density was determined by calculating the percentage of tumor capillary vessel areas/tissue section area. Tissue concentrations of vascular endothelial growth factor and basic fibroblast growth factor were examined by enzyme immunoassay. RESULTS: The levels of endostatin protein estimated by immunoblotting were significantly higher in grade 4 than lower-grade glioma tissues. The immunoreactive bands for endostatin were identified as the fragment derived from noncollagenous domain 1 of collagen XVIII, a peptide 15 residues longer than endostatin toward the NH(2)-terminal end, by NH(2)-terminal amino acid sequencing. In addition to an intense immunoreactivity for endostatin in tumor blood vessels, sections from malignant gliomas showed widely distributed immunoreactivity around tumor cells near the hyperplastic microvessels. The tumor vascular density and the levels of vascular endothelial growth factor in grade 4 glioma tissues were significantly higher than grade 2 and grade 3 gliomas, whereas the levels of basic fibroblast growth factor were the same. CONCLUSIONS: The results indicate a positive correlation between the levels of tissue endostatin and malignancy grades in gliomas. The endostatin may be released near the tumor blood vessels with hyperplasia to counteract angiogenic stimuli in malignant gliomas.

Adult↗

PubMed2001

Calcific deposits on degraded shunt catheters: long-term follow-up of V-P shunts and late complications in three cases.

OBJECT: Three cases with late complications and nine cases without late complications are presented to demonstrate the long-term results of ventriculoperitoneal (V-P) shunting, particularly those concerning degradation and mineral deposits of shunt catheters. METHODS: Plain X-rays were taken in every case to detect any calcification. The catheters removed following late complications were examined in a scanning electron microscope (SEM). Spectroscopy and conventional histology were also performed. CONCLUSION: Routine histology, spectroscopy, and SEM revealed that the mineral deposits consisted of hydroxyapatite. Plain X-ray and operative findings showed that the most extensive calcification was present in the neck, where the catheters were subject to heavy mechanical stress. No calcification was detected on catheters that did not contain barium particles. Our findings indicate that mechanical stress contributes to the process of degradation, and that barium sulfate admixed with silicone during the manufacturing process might accelerate late complications owing to the formation of cracks in the catheters and by enhancing the nucleation rate.

Adolescent↗