Biomedical subjects

T Kawamata

Publications and source records attributed to T Kawamata.

At least 91 records · Page 5Linked to original sources

PubMed1998

Mechanisms of excitatory amino acid release in contused brain tissue: effects of hypothermia and in situ administration of Co2+ on extracellular levels of glutamate.

In order to elucidate the mechanisms of release of EAAs and their excitotoxicity in cerebral contusion, cortical contusion was produced in the rat parietal cortex, and the changes in extracellular levels of EAAs in the central and peripheral areas of contusion were investigated using microdialysis. The cortical contusion induced a rapid increase in dialysate concentration of glutamate ([Glu]d) from a baseline level of 4.6+/-2.8 microM to a maximum level of 36.3+/-12.8 microM. This elevation of glutamate was significantly attenuated by mild hypothermia (32 degrees C for 90 min, comprising 20 min before and 70 min after the injury induction) in the peripheral area of contusion (p < 0.01) but not in the central area. Histological evaluations revealed that the hypothermia reduced the necrosis volume of contusion to 38.3% of that in the normothermic control (p < 0.01). In situ administration of Co2+, an inhibitor of Co2+-dependent exocytotic release of EAAs from the nerve terminals, via the microdialysis system, also attenuated the [Glu]d elevation following cortical contusion, in the peripheral area of contusion (p < 0.01) but not in the central area. These findings indicate that cerebral contusion involves heterogeneous and complex mechanisms of EAA release into the extracellular space. The release of EAAs in the contusion core was nonsensitive to hypothermia and Co2+ administration, suggesting that such EAA release was related to primary disruption of the cell membrane or vascular wall by the physical force of the head trauma, resulting in leakage of EAAs from the metabolic pool in the cytosole or blood stream. In contrast, in the peripheral area, the effectiveness of hypothermia and Co2+ administration implied a presynaptic mechanism of EAA release, which consisted, at least in part, of Ca2+-dependent exocytotic EAA release from depolarized nerve terminals. The EAAs released in the contusion core may diffuse towards a peripheral direction and act on the postsynaptic receptors, causing neuronal depolarization. Such a diffusion-reaction process appears to induce additional release of EAAs from the depolarized nerve terminals. Hypothermia may block this diffusion-reaction process and eventually reduce the contusion volume.

Animals↗

PubMed1998

Premedication with oral dextromethorphan reduces postoperative pain after tonsillectomy.

UNLABELLED: The aim of the present study was to examine whether premedication with dextromethorphan, a clinically available N-methyl-D-aspartic acid (NMDA) receptor antagonist, could reduce postoperative pain after tonsillectomy. Thirty-six patients scheduled for elective bilateral tonsillectomy were investigated in a double-blinded, randomized study. The patients were randomly assigned to one of three groups: control, dextromethorphan 30 mg (Dex 30), and dextromethorphan 45 mg (Dex 45) groups. In the control group, premedication was with oral placebo and intramuscular (i.m.) midazolam and atropine. In the Dex 30 and Dex 45 groups, patients were premedicated with i.m. midazolam and atropine and oral dextromethorphan 30 mg and 45 mg, respectively. Pain was evaluated repeatedly throughout 7 postoperative days, at rest and on swallowing, using a self-rating visual analog scale (VAS). The total doses of analgesics administered postoperatively were also recorded. The Dex 45 group showed significantly lower VAS scores than the control group both at rest and on swallowing throughout the 7 days. The total doses of postoperative analgesics in the Dex 45 group were significantly less than those in the control group. The Dex 30 group showed significantly lower VAS scores than the control group at rest, but not on swallowing. These results indicate that premedication with Dex 45 reduces postoperative pain after tonsillectomy, not only at rest but on swallowing. IMPLICATIONS: Recently, it has been suggested that central sensitization caused by the activation of N-methyl-D-aspartic acid receptors may contribute to the postoperative pain. We found that premedication with 45 mg of dextromethorphan, a clinically available N-methyl-D-aspartic acid receptor antagonist, reduced postoperative pain after tonsillectomy.

Administration, Oral↗

PubMed1998

Induced hypertension improves regional blood flow and protects against infarction during focal ischemia: time course of changes in blood flow measured by laser Doppler imaging.

OBJECTIVE: To characterize changes in regional blood flow (rCBF) during and after a period of arterial occlusion and determine the effect on rCBF and on the extent of infarction when the mean arterial blood pressure is increased during the period of occlusion. METHODS: rCBF in the middle cerebral artery (MCA) territory of rabbits was monitored using laser Doppler perfusion imaging before, during, and after a 1- or 2-hour period of MCA occlusion, and the size of the infarction was assessed by 2,3,5-triphenyltetrazolamine chloride staining after 2 hours of reperfusion. Test animals, the mean arterial blood pressure of which was increased by 65 mm Hg with intravenous phenylephrine during the ischemia, were compared with control animals that remained normotensive. The laser Doppler perfusion imager (Lisca Developments Co., Linköping, Sweden) scanned a 3-cm2 area of cortex with a resolution of 4 mm2 every 15 minutes. RESULTS: MCA occlusion reduced rCBF to 71 +/- 2% of the control level (n = 24, P < 0.001). Hypertension (HTN) restored rCBF to 84 +/- 3% of the control level (n = 12, P < 0.01), but the HTN-induced improvement diminished with time, so that after 1 hour, there was no longer a significant difference between hypertensive and normotensive animals. HTN during the MCA occlusion caused a 97% reduction in infarct size (P < 0.05) in the animals subjected to 1 hour of occlusion but caused only a 45% reduction (P approximately 0.1) in the animals subjected to 2 hours of occlusion. CONCLUSION: This study supports the use of HTN to minimize ischemic injury from short intervals of major intracranial vessel occlusion but fails to demonstrate protection when HTN is maintained during occlusions of more than 1 hour.

Animals↗

PubMed1998

[Involvement of calcineurin A alpha and A beta in neuronal death in a gerbil model of cerebral ischemia].

Treatment with FK506, an inhibitor of Ca2+/calmodulin dependent phosphatase (calcineurin, CaN), within 1 hr after transient ischemia afforded protection from apoptotic death in CA1 pyramidal neurons. To investigate isoform-specific roles of CaN in the neuronal cell death, we localized CaN A alpha and CaN A beta in the gerbil hippocampus using isoform-specific antibodies. In control gerbils, immunoreactions of both isoforms were highly enriched in hippocampal CA1 pyramidal neurons. Four to seven days after the induced ischemia, immunoreactivities of both isoforms were markedly reduced in the CA1 pyramidal cell and lacunosum-molecular layers. The CaN A alpha immunoreactivity was increased in the CA1 radiatum and oriens layers, whereas that of CaN A beta was enhanced in reactive astrocytes in the CA1 region. These findings suggest that CaN A alpha is involved in sprouting of afferent fibers in CA1 and that CaN A beta is involved in the reaction of astrocytes such as assembly of glial fibril acidic protein.

Animals↗

PubMed1998

Localization and possible functions of presenilins in brain.

Presenilin-1 (PS-1) is localized to chromosome 14 and presenilin-2 (PS-2) to chromosome 1. Mutations in these genes, primarily in PS-1, account for an estimated 60% of early onset familial Alzheimer's disease cases (FAD), while FAD cases account for about 10% of all Alzheimer's disease (AD) cases. The mutations are minor but are 100% penetrant, suggesting that the proteins have acquired a toxic gain in function. The proteins have multiple transmembrane domains and have been reported to be localized to the Golgi apparatus, endoplasmic reticulum, nuclear membranes and cell surface membranes. They are thought to have functions associated with vesicular trafficking, Notch signaling and apoptosis. PS mutants show relative increases in the amount of A beta42/43 compared with A beta40 in plasma, fibroblasts and brain, observations which have been taken as a possible mechanism of their role in AD. In brain, the mRNAs for these two genes are localized primarily in neurons, with the strongest in situ hybridization signals being observed in the hippocampus, cerebellum and cerebral cortex. In AD, signals detected in the hippocampus are weaker than those in normals, while signals in the cerebellum are comparable. Immunohistochemical localization of the proteins is also primarily in neurons, and, at least for PS-1, is reduced in AD affected areas. PS-1 is localized to granular structures which are most abundant in cell bodies and dendrites. The functions of the presenilins are not yet known, but available evidence points to pyramidal neurons as the most logical site for pathological change in AD.

Alzheimer Disease↗

PubMed1998

[Multiple bacterial aneurysms: case report].

A 59-year-old man presented with an internal carotid artery (ICA) bacterial aneurysm which ruptured during surgery for treatment of another bacterial aneurysm. He had been admitted to our hospital because of the recurrence of colon cancer. He had undergone aortic and mitral valve replacement because of closure incompetence due to bacterial endocarditis two months previously. Two months after treatment for colon cancer, he developed fever, and arterial blood culture demonstrated. Staphylococcus epidermidis. A few days later, he suddenly suffered severe headache and vomiting, followed by deterioration of consciousness. CT showed subarachnoid hemorrhage and angiography showed a saccular aneurysm at the opercular portion of the left middle cerebral artery (MCA). Immediate clipping of the aneurysm was attempted. The carotid cistern was opened via a left frontotemporal craniotomy, but an ICA aneurysm, which had not been previously recognized, ruptured suddenly. The ICA aneurysm was wrapped with Vascwrap with some difficulty. The MCA aneurysm was then trapped. Postoperatively, the patient continued to be stuporous for a few days. Two weeks later, he died of complications caused by pneumonia. Bacterial aneurysm is more likely to be located in the distribution of the distal arterial tree, mainly in the distribution of the MCA. The difficulty of preoperative diagnosis and the unpredictable clinical course of bacterial aneurysms are emphasized.

Aneurysm, Infected↗

PubMed1998

[Evaluation of risks for postoperative pulmonary complications using a preoperative consultation system].

We retrospectively investigated the perioperative management and postoperative pulmonary complications of patients who had preoperative respiratory problems and consultations with anesthesiologists. These patients numbered eight hundred, 23.7% of all patients who had preoperative consultations, and 40.9% and 62.0% of the 800 had preoperative and postoperative respiratory management, respectively. Forty eight patients (6.0%) received postoperative artificial respiration. One hundred and twenty four patients (15.5%) had some respiratory complications post-operatively, and 5 patients (0.7%) died mainly because of the complications. In an evaluation of these patients with the modified predicted risk factors of Okutsu including the obesity factor and smoking history, there was no respiratory complication in patients under 14 points. Patients with high points of more than 20 included almost all of the patients (114 patients, 91.9%) who had postoperative respiratory complications. We conclude that our preoperative consultation system works well and that the modified predicted-risk factors for postoperative pulmonary complications is useful for the standardization and objectivity of preoperative patient evaluation.

Humans↗

PubMed1998

[Large distal anterior cerebral artery aneurysm associated with azygos anterior cerebral artery: case report].

A 51-year-old woman presented with a distal anterior cerebral artery aneurysm (DACAA) manifesting as severe headache and monoparesis of the left lower limb. Computed tomography revealed subarachnoid hemorrhage in the interhemispheric fissure, bilateral sylvian fissures, and basal cistern, and a hematoma in the supracallosal region. Angiography showed a large aneurysm (23 x 18 mm) located on the distal end of the azygos anterior cerebral artery (azygos ACA) at the supracallosal portion. T2-weighted magnetic resonance imaging demonstrated the hematoma as a mixed intensity mass, compressing the corpus callosum downward, and the aneurysm as a flow void anterior to the hematoma. Unilateral frontoparietal parasagittal craniotomy was performed with a horse-shoe shaped incision. The aneurysm was clipped via the interhemispheric approach, and the hematoma was aspirated. Postoperative angiography showed disappearance of the aneurysm and intact azygos ACA. The patient was discharged with mild monoparesis, paresthesia of the left lower limb and diagnostic dyspraxia. DACAA almost always arises at or near the genu of the corpus callosum and is often associated with vascular anomaly. In the literature, 22 of 26 cases of large and giant DACAA were located at or near the genu, but only 3 cases, including ours, in the supracallosal area. 11 cases were associated with azygos ACA. Therefore, hemodynamic stress caused by vascular anomaly may be involved in the formation of large or giant DACAA in contrast with cases of normal DACAA.

Cerebral Arteries↗

PubMed1998

[A resolving sign of acute subdural hematoma: from report of two cases].

A 7-year-old-boy (Case 1) and a 60-year-old-man (Case 2) presented with rare spontaneous resolution of acute subdural hematoma (ASDH). They were admitted with consciousness disturbance, drowsy in Case 1 and sleepy in Case 2. Initial CT showed ASDH associated with a low density band between the hematoma and the inner wall of the skull base, combined with right parietal contusion in Case 2. Repeat CT showed that the hematoma had resolved spontaneously after a few hours, and the patients regained clear consciousness next day in Case 1 within a few days in Case 2 without surgical treatment. The mechanism of spontaneous resolution of ASDH was thought to involve pulsatile flow of cerebrospinal fluid (CSF) through the tear in the arachnoid membrane, resulting in redistribution and dispersal of the hematoma, and retrograde flow into the subarachnoid space. The characteristic feature of the CT findings, the low density band between the hematoma and the inner wall of the skull bone, probably shows this process. Spontaneous resolution of ASDH requires that the brain compensatory function maintains the normal outflow of CSF, and controls the intracranial pressure by CSF buffering, blood outflow via the venous system, and brain elasticity. The low density band may be a useful finding to distinguish cases with good and bad prognosis.

Acute Disease↗

PubMed1997

A novel missense mutation in the presenilin-1 gene in a familial Alzheimer's disease pedigree with abundant amyloid angiopathy.

A number of missense mutations associated with early-onset familial Alzheimer's disease have been reported in the presenilin-1 gene. The mutations were demonstrated to cluster in specific regions of the the protein. We report here a novel missense mutation at the C-terminus of the third transmembrane domain in the presenilin-1 protein in a family of Japanese origin with early-onset Alzheimer's disease. This mutation is located at a site that is different from the sites at which mutations are known to cluster. Although the clinical phenotype is similar to those of pedigrees associated with other presenilin-1 mutations, postmortem examination of this pedigree revealed heavy amyloid deposits in the walls of small meningeal arteries as well as around small vessels within the brain parenchyma. These results indicate that a mutation at the C-terminus of the third transmembrane domain in the presenilin-1, which is a novel site for mutations, may play a key role in Alzheimer's pathogenesis.

Adult↗

PubMed1997

Intracisternal basic fibroblast growth factor enhances functional recovery and up-regulates the expression of a molecular marker of neuronal sprouting following focal cerebral infarction.

Focal cerebral infarction (stroke) due to unilateral occlusion of the middle cerebral artery in mature rats produces deficits in sensorimotor function of the contralateral limbs that recover partially over time. We found that biweekly intracisternal injection of basic fibroblast growth factor (bFGF; 0.5 microg/injection), a potent neurotrophic polypeptide, markedly enhanced recovery of sensorimotor function of the contralateral limbs during the first month after stroke without apparent adverse side effects. Immunostaining for growth-associated protein 43 (GAP-43), a molecular marker of axonal sprouting, showed a selective increase in GAP-43 immunoreactivity in the intact sensorimotor cortex contralateral to cerebral infarcts following bFGF treatment. These results show that bFGF treatment can enhance functional recovery after stroke, and that the mechanism may include stimulation of neuronal sprouting in the intact brain.

Animals↗

PubMed1997

Cloning of the cDNA encoding rat Presenilin-1.

We isolated rat presenilin-1 (PS-1; also called S182 previously) cDNA from total brain RNA by using a reverse transcription-polymerase chain reaction (RT-PCR) technique with primers homologous to the conserved sequences of human and mouse PS-1. Rat PS-1 cDNA encoded 468 amino acids (aa) and the deduced aa sequence was highly homologous to those of the human (88.4%) and mouse (92.7%). Northern blot analysis of the rat PS-1 cDNA revealed two mRNA species in rat neurotypic pheochromocytoma and glioma cell lines (PC-12 and C6, respectively) that migrated at rates corresponding to approximately 3.0 and 7.5 kb.

Alzheimer Disease↗

PubMed1997

Hemodynamic depression and microthrombosis in the peripheral areas of cortical contusion in the rat: role of platelet activating factor.

Cerebrovascular damages leading to subsequent reductions in regional cerebral blood flow (rCBF) may play an important role in secondary cell damages following traumatic brain injury (TBI). Recent studies have demonstrated that rCBF markedly decrease in experimental model of TBI (e.g. fluid percussion injury, acute subdural hematoma, contusion). However, precise mechanisms underlying post-traumatic CBF reduction remain unclear. In the present study, the rCBF changes and microthrombosis formation were investigated in a cortical contusional model in rats, and the effects of etizolam (platelet activating factor antagonist) on microthrombosis were tested. The rCBF in the peripheral areas increased transiently, and decreased to ischemic level 3 hours post- injury. The histological examinations revealed microthrombosis formation in the contused area, extending from the center to the peripheral areas within 6 hours post-injury. The rCBF decrease and the contusion necrosis volume were significantly attenuated by etizolam administration. These results indicate that platelet activating factor is involved in microthrombosis formation and hemodynamic depression, and resultant ischemic damages within areas surrounding the contusion.

Animals↗

PubMed1997

Antioxidant, OPC-14117, attenuates edema formation and behavioral deficits following cortical contusion in rats.

Oxygen free radicals may contribute to tissue injury processes in the central nervous system following ischemia or trauma. Recent studies have suggested that inhibition of free radicals improves the outcome in experimental models involving such conditions, and antioxidant therapy appears promising. In the present study, behavioral changes and edema formation in rat cortical contusion model were investigated, and the effects of a superoxide radical scavenger, OPC-14117, were tested. Wistar rats were anesthetized with halothane inhalation. Cortical contusion was induced in the parietal cortex employing a controlled cortical impact device. Immediately following injury induction, OPC-14117 was administered (300 mg/kg, p.o.). Edema formation was assessed in the center and peripheral areas of the contusion by the specific gravity method. Behavioral changes were evaluated by the Morris water maze test and the habituation of exploratory activity. The results revealed that the vehicle-administered control showed progressive edema formation and behavioral deficits following the injury. These changes were significantly attenuated by the OPC-14117 treatment (p < 0.05). Further, OPC-14117 reduced the size of contusional necrosis (p < 0.05). These findings suggest that superoxide free radicals are involved in contusion-induced edema formation, necrosis formation, and behavioral deficits, and that OPC-14117 has a therapeutic potential to prevent secondary cell damage following traumatic brain injury.

Animals↗

PubMed1997

Antinociceptive interaction of intrathecal alpha2-adrenergic agonists, tizanidine and clonidine, with lidocaine in rats.

BACKGROUND: The intrathecal alpha2-adrenergic agonist, clonidine, has been shown to have considerable antinociceptive effect, although clonidine causes hypotension and bradycardia. The combination of intrathecal clonidine and local anesthetics enhances analgesic effects, whereas the combination may cause marked hypotension and motor blockade, which may limit the clinical application of the combination. Tizanidine, another alpha2-adrenergic agonist, has also provided antinociception without producing pronounced hemodynamic changes. This study was designed to evaluate the antinociceptive and hemodynamic interactions of tizanidine and clonidine with lidocaine. METHODS: Male Sprague Dawley rats were chronically implanted with lumbar intrathecal catheters. The tail-flick test was used to assess the thermal nociceptive threshold. The ability of intrathecal tizanidine, clonidine, lidocaine, or the combinations of alpha2-adrenergic agonist and lidocaine to alter the tail-flick latency was examined. To characterize the antinociceptive interaction, the isobolographic analysis was applied. Additionally, the motor function, blood pressure and heart rate after intrathecal administration of drugs and combinations were also monitored. RESULTS: Intrathecal tizanidine, clonidine, or the combinations increased the tail-flick latency in dose- and time-dependent fashion without affecting motor function. The order potencies (dose producing a 50% of peak effect, in microg) of tizanidine and clonidine were 1.8 and 0.75, respectively. With isobolographic analysis, tizanidine with lidocaine and clonidine with lidocaine showed significantly synergistic antinociceptive interaction. Potency ratio analysis and fractional analysis also confirmed the synergistic interaction. At the doses in the combinations showing comparable antinociception, tizanidine with lidocaine, unlike clonidine with lidocaine, did not affect motor function or blood pressure. CONCLUSION: The authors' results show that intrathecal tizanidine and clonidine synergistically interact with lidocaine so that the degree of antinociception to somatic noxious stimuli are enhanced. The antinociceptive synergistic interaction between tizanidine and lidocaine may be useful in clinical practice without affecting blood pressure, heart rate, or motor function.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1997

Establishment of a murine model for metastasis of cytokine-producing tumor to the brain.

The A375 cell line, derived from human malignant melanoma, has characteristics of interleukin-6 (IL-6) production. By using this cell line, we have investigated a murine metastasis model of IL-6-producing tumors to the brain by injecting A375 cells directly into the left cardiac ventricle. Nude mice were anesthetized with intraperitoneal injection of pentobarbital sodium. Next, A375 cells suspended in phosphate-buffered saline (PBS) were injected into the left cardiac ventricle of mice. An intracardiac injection of 10(5) cells developed tumor colonies in the brain after 4 to 6 weeks. Metastatic cells were found in every lobe of the brain. An immunocytochemical study revealed IL-6 production by A375 cells at the metastatic sites in the brain. By the transfection of genes encoding proteins into A375 cells, a novel model of protein expression in the brain in vivo could be constructed. Our system does not require great skill. Our experimental model will facilitate future studies of the local effects of proteins in the brain.

Animals↗

PubMed1997

Possible different mechanism between amyloid-beta (25-35)-and substance P-induced chemotaxis of murine microglia.

The mechanism of murine microglial chemotaxis induced by amyloid-beta protein (A beta (25-35)) was investigated. A beta (25-35) dose-dependently stimulated microglial chemotaxis at concentrations between 100 pM and 10 nM. Substance P, a NK-1 agonist, stimulated chemotaxis at concentrations of 10 nM or more. GR-64349, a NK-2 agonist, and senktide, a NK-3 agonist, did not stimulate microglial chemotaxis. We examined whether homologous desensitization of chemotaxis would occur by A beta (25-35). The chemotactic effect of microglia was homologously desensitized by 10 nM A beta (25-35). On the other hand, substance P at 10 nM did not desensitize the A beta (25-35)-induced chemotaxis. These data show that A beta (25-35) induces the chemotaxis of microglia probably through a receptor other than the NK-1 receptor.

Amyloid beta-Peptides↗

PubMed1997

Augmentation of both hemolysate-induced contraction and activation of protein kinase C by submaximum activation in canine cerebral arteries in vitro.

Although phorbol esters, synthetic activators of protein kinase C (PKC), can stimulate large increases in the binding of cytosolic PKC to form membrane-bound PKC (PKCm, an indicator of PKC activation), the authors report that even small increases in PKCm induced by phorbol esters (8-12% of total PKC content) can be associated with significant PKC-mediated contractions in vitro (50-85% of maximum) in normal canine cerebral arteries. Increases in PKCm of similarly small magnitude were found in vitro when control artery segments were exposed to hemolysate, but only if the arterial smooth-muscle cells were first slightly depolarized by increased extracellular potassium to values of membrane potential similar to those observed in canine cerebral arteries during chronic cerebral vasospasm. These increases in PKCm (6-8% of total PKC content) coincided with a greatly augmented contractile response to hemolysate. These results show that the previous observation of only a small increase in PKCm (approximately 7% of total PKC content) after experimental subarachnoid hemorrhage in the canine model does not preclude a potentially important role for PKC-mediated contraction in the pathogenesis of cerebral vasospasm.

Animals↗