50 results on '"Kusaka G"'
Search Results
2. Risk of metachronous recurrence after endoscopic submucosal dissection of esophageal squamous cell carcinoma
- Author
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Uno, K., primary, Koike, T., additional, Kusaka, G., additional, Takahashi, Y., additional, Ara, N., additional, and Shimosegawa, T., additional
- Published
- 2017
- Full Text
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3. P490: Electrooculogram and trigeminal nerve evoked potentials during neurosurgical operations
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Ishikawa, M., primary, Kiryu, N., additional, Ikoda, M., additional, Yamaguro, T., additional, Ebihara, A., additional, Kusaka, G., additional, and Tanaka, Y., additional
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- 2014
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4. Arytenoid adduction combined with medialization laryngoplasty under general anesthesia using a laryngeal mask airway.
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Kanazawa T, Watanabe Y, Hara M, Shinnabe A, Kusaka G, Murayama T, and Iino Y
- Published
- 2012
5. One-stage anterior approach for four-vessel occlusion in rat.
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Yamaguchi M, Calvert JW, Kusaka G, Zhang JH, Yamaguchi, Mitsuo, Calvert, John W, Kusaka, Gen, and Zhang, John H
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- 2005
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6. Prospective analysis of risk for bleeding after endoscopic biopsy without cessation of antithrombotics in Japan
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Ara, N., Iijima, K., Maejima, R., Yutaka Kondo, Kusaka, G., Hatta, W., Uno, K., Asano, N., Koike, T., Imatani, A., and Shimosegawa, T.
7. The Early Postoperative Course of Cognitive Function and Preoperative Cerebrovascular Reserve.
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Ikota M, Ishikawa M, and Kusaka G
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- Humans, Middle Cerebral Artery diagnostic imaging, Middle Cerebral Artery surgery, Cognition physiology, Magnetic Resonance Imaging, Risk Factors, Temporal Arteries surgery, Cerebrovascular Circulation physiology, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction etiology, Cerebral Revascularization methods
- Abstract
Background: Patients with severe steno-occlusive disease of a main cerebral artery without causative lesions on magnetic resonance imaging (MRI) often develop cognitive impairment. However, the effects of revascularization surgery and the source of the cognitive impairment remain unclear. Therefore, we investigated the early postoperative course of cognitive function and its association with cerebral blood flow (CBF), cerebrovascular reserve (CVR), white matter disease (WMD), lacunar infarction, and cerebrovascular risk factors., Methods: Cognitive function was examined using neurobehavioral cognitive status examination (COGNISTAT) in 52 patients with steno-occlusive disease of a main cerebral artery before and at 6 months after superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. We examined how cognition changed before and at 1, 3, and 6 months after STA-MCA anastomosis in 27 of 52 patients. CVR and CBF were calculated from
123 I-N-isopropyl-p-iodoamphetamine single photon emission computed tomography, in addition to other cerebrovascular risk factors in 34 of 52 patients. Cerebral infarction and WMD (periventricular hyperintensity [PVH] and deep subcortical white matter hyperintensity) were also evaluated preoperatively by MRI., Results: COGNISTAT scores improved at 1 month after STA-MCA anastomosis in patients with severe steno-occlusive disease of a main cerebral artery. Multiple stepwise regression analysis revealed that CVR (regression coefficient = -2.237, p = 0.0020) and PVH (regression coefficient = 2.364, p = 0.0029) were the best predictors of postoperative improvement in COGNISTAT scores ( R2 = 0.415; p = 0.0017)., Conclusion: Cognitive function improves in relation to preoperative CVR and PVH early after STA-MCA anastomosis in patients with steno-occlusive disease of a main cerebral artery., Competing Interests: None declared., (Thieme. All rights reserved.)- Published
- 2024
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8. Ultrasonography monitoring with Superb Microvascular Imaging during cerebrovascular surgery.
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Ishikawa M, Uchiyama T, Okawa A, Soma N, Ikota M, Aoki K, Naritaka H, and Kusaka G
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- Humans, Contrast Media, Ultrasonography, Cerebral Hemorrhage diagnostic imaging, Cerebral Hemorrhage surgery, Cerebrovascular Circulation, Moyamoya Disease diagnostic imaging, Moyamoya Disease surgery, Carotid Stenosis, Intracranial Aneurysm diagnostic imaging, Intracranial Aneurysm surgery, Hemangioblastoma
- Abstract
Introduction: Ultrasonography (US) is used as a real-time dynamic imaging modality during neurosurgery. A novel Doppler US technique, Superb Microvascular Imaging (SMI), can be used to visualize low-velocity flow of small vessels at high resolution with high frame rates. We visualized vessel flow using this US SMI technique and contrast agent during cerebrovascular surgery., Methods: Forty-three patients with an unruptured cerebral aneurysm (control), ischemic and hemorrhagic moyamoya disease, carotid artery stenosis, hemangioblastoma, severe stenosis of the middle cerebral artery, venous angioma, and intracerebral hemorrhage (ICH) underwent neurosurgery with US SMI monitoring using a contrast agent. The diameter, length, and number of penetrating vessels were analyzed in patients with an unruptured cerebral aneurysm (control), moyamoya disease, and ICH., Results: Diameter and length of cerebral penetrating vessels were significantly increased in patients with moyamoya disease and ICH compared to control patients. The number of penetrating vessels was increased in moyamoya disease patients compared to control and ICH patients. In hemorrhagic moyamoya disease, flow in the penetrating vessels originated from a deep periventricular point and extended to the cerebral surface. Pulsatile cerebral aneurysms during clipping surgery and carotid artery stenosis during carotid endarterectomy were easily identified by SMI. Drastically increased vessel flow in patients with a hemangioblastoma or a venous angioma was observed., Conclusion: Using the US SMI technique and contrast agent, we obtained useful flow information of the vascular disease structure and intracerebral deep small vessels during cerebrovascular surgery. Further quantitative analysis will be informative and helpful for cerebrovascular surgery., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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9. Clinical case of lung spindle cell carcinoma markedly responsive to pembrolizumab.
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Mizushina Y, Ohyanagi F, Shiihara J, Nomura M, Ohta H, Oshiro H, Tsubochi H, Kusaka G, and Yamaguchi Y
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- Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, B7-H1 Antigen metabolism, Brain Neoplasms secondary, Carcinoma secondary, Humans, Lung Neoplasms pathology, Male, Middle Aged, Pneumonectomy methods, Thoracic Neoplasms secondary, Antibodies, Monoclonal, Humanized therapeutic use, Brain Neoplasms therapy, Carcinoma therapy, Lung Neoplasms therapy, Thoracic Neoplasms therapy
- Abstract
A 52-year-old man underwent pneumonectomy of the left lung for previously diagnosed primary spindle cell carcinoma (pT4aN1M0, stage III B) with programmed death-ligand 1 expression (tumor proportion score ≥95%) and without epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase fusion gene. However, brain metastasis and chest wall tumor relapse occurred. Considering insufficient improvement with gamma knife treatment for brain metastasis and combination chemotherapy (paclitaxel, carboplatin, and bevacizumab), pembrolizumab monotherapy and palliative irradiation therapy for chest metastases were started after brain tumor volume reduction using craniotomy. Brain edema and chest wall metastases markedly improved following a pseudoprogression of the brain edema accompanied by a performance status decline; this effect continued until 11 cycles of pembrolizumab administration., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)
- Published
- 2021
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10. Clinical Features of Esophageal Eosinophilia According to Endoscopic Phenotypes.
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Kon T, Abe Y, Sasaki Y, Kikuchi R, Uchiyama S, Kusaka G, Yaoita T, Yagi M, Shoji M, Onozato Y, Mizumoto N, and Ueno Y
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- Adolescent, Adult, Deglutition Disorders epidemiology, Eosinophilic Esophagitis epidemiology, Female, Humans, Japan epidemiology, Male, Middle Aged, Phenotype, Prevalence, Retrospective Studies, Sex Factors, Young Adult, Deglutition Disorders diagnosis, Deglutition Disorders physiopathology, Eosinophilic Esophagitis diagnostic imaging, Eosinophilic Esophagitis physiopathology, Esophagoscopy methods, Symptom Assessment methods
- Abstract
Objective Esophageal eosinophilia (EE), a histological hallmark of eosinophilic esophagitis, is classified into two endoscopic phenotypes: localized and diffuse EE. Our aim was to determine the prevalence of EE localized in the lower esophagus and to describe its clinical features in comparison with diffuse EE. Methods Data from 81 consecutive patients with EE were retrospectively investigated. EE was histologically defined as ≥15 eosinophils per high-power field. Based on the endoscopic appearance with a histological assessment, EE was classified as either diffuse or localized type. We compared the clinical features, including the medical treatment and natural course, between the two types. Results Of the 81 patients, 52 (64.2%) had diffuse EE, and 29 (35.8%) had localized EE. Among men patients, localized EE was significantly more common than diffuse EE. In localized EE, dysphagia and food impaction were less prevalent, and the presence of rings was significantly less common than in diffuse EE. Acid-suppressive therapy was administered to only 3 of the 29 patients with localized EE. In asymptomatic patients, especially those with localized EE, endoscopic abnormalities did not worsen but rather improved in some findings, such as with regard to furrows or exudate, during the natural course of three years without medical treatment. Conclusion Localized EE has a strong predilection for men patients and accounted for more than one third of all cases of EE. This condition appears to be less symptomatic and necessitates milder medical treatment than diffuse EE and might not worsen progressively.
- Published
- 2020
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11. Promoter methylation of galanin receptors as epigenetic biomarkers for head and neck squamous cell carcinomas.
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Kanazawa T, Misawa K, Shinmura K, Misawa Y, Kusaka G, Maruta M, Sasaki T, Watanabe Y, and Carey TE
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- Epigenesis, Genetic, Female, Humans, Male, Promoter Regions, Genetic, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, DNA Methylation, DNA, Neoplasm genetics, DNA, Neoplasm metabolism, Head and Neck Neoplasms genetics, Head and Neck Neoplasms metabolism, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Receptors, Galanin genetics, Receptors, Galanin metabolism, Squamous Cell Carcinoma of Head and Neck genetics, Squamous Cell Carcinoma of Head and Neck metabolism
- Abstract
Introduction: While remarkable progress has been made in standard treatments for head and neck squamous cell carcinomas (HNSCCs), the long-term survival remains at an unsatisfactory 40-50%. To improve the survival rate, biomarkers for optimal treatment selection and prognostic prediction, as well as novel, low-toxicity treatment strategies, are required. Galanin receptor (GALR) 1 and GALR2 are well-studied tumor suppressors in HNSCCs. Compared with other clinicopathological factors, the epigenetic variants of GALRs have been found to be the most powerful markers to predict the prognosis of HNSCC patients. Areas covered: This review outlines the functions and signaling pathways of GALRs and explains the potential of GALR promoter methylation as a biomarker for HNSCC prognosis. We also summarize recent developments in promoter methylation studies in HNSCC and indicate future directions for GALR promoter methylation studies. Expert commentary: GALR studies have highlighted two major aspects with implications in HNSCC - that G-protein coupled receptors (GPCRs) act as tumor suppressor genes and that GALR promoter methylation is significantly related to the carcinogenesis of HNSCC. The findings of GALR studies can be applied to studies on other GPCRs and further in-depth DNA methylation studies. Deeper insights into GPCR epigenetics are expected to markedly improve HNSCC treatment.
- Published
- 2019
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12. Epigenetic inactivation of galanin receptors in salivary duct carcinoma of the parotid gland: Potential utility as biomarkers for prognosis.
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Kanazawa T, Misawa K, Fukushima H, Misawa Y, Sato Y, Maruta M, Imayoshi S, Kusaka G, Kawabata K, Mineta H, Carey TE, and Nishino H
- Abstract
Salivary duct carcinoma (SDC) constitutes one of the most aggressive cancers in the salivary gland and is associated with a poor prognosis; however, no established systemic therapy options are available. SDC exhibits biological similarity to prostate and breast cancers, therefore anti-hormone therapy and molecular target therapies are available, however with limited beneficial effects. Galanin and galanin receptors (GALRs) are well established as molecular biomarkers to predict the survival rate and risk of recurrence of head and neck squamous cell carcinoma. The present study investigated the clinicopathological features of patients with SDC and the methylation status of their galanin and GALR genes to demonstrate the prognostic value for this disease. The median overall survival (OS) was 37.2 months. T-stage, N-stage, disease stage, tumor size, and preoperative facial paralysis were significantly associated with OS, whereas human epidermal growth factor receptor 2 (HER2) overexpression was not. GALR1 and GALR2 methylation rates in tumor tissues were significantly increased compared with normal tissues with 9.85- and 4.49-fold increase, respectively. p27
kip1 and p57kip2 expression significantly inversely correlated with the methylation rate of GALR1 and GALR2 . In addition, the observed GALR1 and/or GALR2 methylation rates were significantly correlated with a decrease in OS. These results suggest that GALR1 and GALR2 may serve as potential prognostic factors and therapeutic targets in SDC.- Published
- 2018
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13. Superficial Temporal Artery-middle Cerebral Artery Anastomosis for Ischemic Stroke due to Dissection of the Intracranial Internal Carotid Artery with Middle Cerebral Artery Extension.
- Author
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Ikota M, Kusaka G, and Tanaka Y
- Abstract
A 31-year-old man presented with a sudden-onset headache, right hemiparesis, and dysarthria on day 0 and was diagnosed with acute ischemic stroke due to dissection of the left intracranial internal carotid artery with middle cerebral artery extension. His symptoms progressed despite the institution of treatment, suggesting progression of the dissection. On day 5 after symptom onset, the patient underwent superficial temporal artery-middle cerebral artery anastomosis. No new ischemic stroke event occurred after surgery. Cerebral angiography performed 6 months after surgery showed spontaneous resolution of the dissection. The patient recovered to a modified Rankin Scale score of 2 and was able to return to work. The results of the present case suggest that superficial temporal artery-middle cerebral artery anastomosis is an effective treatment for ischemic stroke due to dissection of the intracranial internal carotid artery with middle cerebral artery extension., Competing Interests: Conflicts of Interest Disclosure The authors declare that they have no conflicts of interest. All authors who are members of The Japan Neurosurgical Society (JNS) have registered online Self-reported COI Disclosure Statement Forms through the website for JNS members.
- Published
- 2018
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14. Design of a Locator for Designing the Shortest Incision for a Polygonal Dural Window.
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Nagai M, Kaneko N, Arai F, Kusaka G, and Ishikawa M
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- Humans, Mathematical Concepts, Suture Techniques, Dura Mater surgery, Neurosurgical Procedures methods
- Abstract
When a wide polygonal dural window is created, a short dural incision length is preferred by surgeons because suturing a wastefully long incision line during closure is troublesome. A locator to facilitate making the shortest dural incision when creating a polygonal dural window would be helpful. We geometrically analyzed the shortest incision design for a pentagonal dural window and produced a simple locator for intraoperatively implementing this design. The design for a pentagonal dural window with the shortest incision is the same as the design for a minimum Steiner tree (MST) problem with five vertices. The MST consists of three interconnected Steiner points (SPs) with three equal, radiating branches. We produced a template of the features of the MST for a polygon (MST template) as a locator. The MST template consists of several uniform Steiner units (SUs), each of which has an SP at the center and three wings that branch off of the SP, and each SU also has three slits through which the wings of another unit can pass. This mechanism allows us to freely adjust the distance between the SPs of separate SUs. In clinical practice, we can create the shortest incision design for a quadrilateral or pentagon by arranging MST templates combining two or three SUs. If we open a wide dural window, the total incision lengths created using our method are 1-5 cm shorter than conventional incisions. The MST template accurately and easily reveals the shortest incision design.
- Published
- 2017
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15. Clinical significance of the coexistence of carotid artery plaque and white matter disease in patients with symptomatic cerebral infarction.
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Ishikawa M, Sugawara H, Tsuji T, Nagai M, Kusaka G, and Naritaka H
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- Aged, Aged, 80 and over, Brain Ischemia complications, Carotid Intima-Media Thickness adverse effects, Carotid Stenosis complications, Carotid Stenosis diagnosis, Cerebral Infarction complications, Cerebral Infarction diagnosis, Female, Humans, Ischemic Attack, Transient complications, Magnetic Resonance Imaging methods, Male, Middle Aged, Plaque, Atherosclerotic complications, Plaque, Atherosclerotic diagnosis, Risk Factors, Brain Ischemia pathology, Carotid Stenosis pathology, Cerebral Infarction pathology, Plaque, Atherosclerotic pathology
- Abstract
Objectives: Symptomatic cerebral infarction (CI) can occur in patients without main cerebral artery stenosis or occlusion. This study investigated the unique features of carotid artery plaque and white matter disease (WMD) in patients with symptomatic CI and transient ischemic attack (TIA) but without stenosis or occlusion of a main cerebral artery., Patients and Methods: We studied 647 patients who underwent both carotid ultrasound examination and brain magnetic resonance images. Plaque score (PS), plaque number, maximal plaque intima-media thickness and grades of WMD were examined. Subjects were divided into four groups, the CI group, TIA group, myocardial infarction (MI) group and risk factor (RF) group. Plaque and WMD were analyzed in cerebral ischemia group (CI and TIA), compared to non-cerebral ischemia groups and to a high PS group and a high WMD grade group from the RF group., Results: Both of each value of plaque and grades of WMD in the cerebral ischemia group were significantly higher than those in other groups. Grades of WMD in the cerebral ischemia group were significantly higher than those in the high PS group, although there was no significant difference of the each value of plaque between the two groups. The each value of plaque in the cerebral ischemia group was also significantly higher than those in the high WMD grade group, although there was no significant difference of grade of WMD between the two groups., Conclusion: Simultaneous increases in carotid artery plaque and WMD are associated with symptomatic CI, which is not caused by stenosis or occlusion of a main cerebral artery., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
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16. Cochlear Nerve Action Potential Monitoring for Preserving Function of an Unseen Cochlear Nerve in Vestibular Schwannoma Surgery.
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Ishikawa M, Kojima A, Terao S, Nagai M, Kusaka G, and Naritaka H
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- Humans, Male, Microvascular Decompression Surgery methods, Middle Aged, Monitoring, Intraoperative methods, Neuroma, Acoustic diagnosis, Neuroma, Acoustic physiopathology, Neurosurgical Procedures methods, Cochlea surgery, Cochlear Nerve surgery, Evoked Potentials, Auditory, Brain Stem physiology, Hearing physiology, Neuroma, Acoustic surgery
- Abstract
Background: Intraoperative monitoring of cochlear nerve action potential (CNAP) has been used in patients with small vestibular schwannoma (<15 mm) to preserve cochlear nerve function. We performed surgery for a larger vestibular schwannoma under CNAP monitoring with the aim of preserving cochlear nerve function, and compared the data with findings from 10 patients with hemifacial spasm who underwent microvascular decompression surgery., Case Description: We report the case of a patient with a 26-mm vestibular schwannoma and normal hearing function who underwent neurosurgery under electrophysiological monitoring of the facial and cochlear nerves. Amplitudes of evoked facial muscle responses were maintained at approximately 70% during the operation. The latency of wave V on brainstem auditory evoked potential (BAEP) increased by 0.5 ms, and amplitude was maintained at approximately 70% of the value at the beginning of the operation. Latencies of P1, N1, and P2 on CNAP did not change intraoperatively. These latencies were comparable to those of 10 normal patients with hemifacial spasm. CNAP monitoring proved very useful in confirming the location of the cochlear nerve in the operative field and preserving cochlear nerve function. Both facial nerve function and hearing acuity were completely preserved after tumor removal, and wave V latency on BAEP returned to normal and was maintained in the normal range for at least 2 years., Conclusions: CNAP monitoring is extremely useful for preserving the function of the unseen cochlear nerve during vestibular schwannoma surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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17. Improvement of neurovascular function and cognitive impairment after STA-MCA anastomosis.
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Ishikawa M, Kusaka G, Terao S, Nagai M, Tanaka Y, and Naritaka H
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- Aged, Anastomosis, Surgical, Carotid Artery, Internal diagnostic imaging, Carotid Artery, Internal physiopathology, Carotid Stenosis complications, Carotid Stenosis physiopathology, Carotid Stenosis psychology, Cerebrovascular Circulation, Cognition physiology, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction etiology, Cognitive Dysfunction physiopathology, Female, Humans, Infarction, Middle Cerebral Artery complications, Infarction, Middle Cerebral Artery physiopathology, Infarction, Middle Cerebral Artery psychology, Linear Models, Male, Middle Cerebral Artery diagnostic imaging, Middle Cerebral Artery physiopathology, Neuropsychological Tests, Recovery of Function, Temporal Arteries diagnostic imaging, Temporal Arteries physiopathology, Tomography, Emission-Computed, Single-Photon, Treatment Outcome, Carotid Stenosis surgery, Cerebral Revascularization, Cognitive Dysfunction surgery, Infarction, Middle Cerebral Artery surgery, Middle Cerebral Artery surgery, Temporal Arteries surgery
- Abstract
Objective: In patients with severe steno-occlusive disease of a main cerebral artery, decreased cerebrovascular reserve (CVR) and cognitive impairment without causative focal lesions on magnetic resonance imaging have been reported. We examined ipsilateral and contralateral CVR and cognition before and after superficial temporal artery-middle cerebral artery (MCA) anastomosis operation in patients with internal carotid artery (ICA) or MCA occlusion., Methods: In 30 patients with ICA or MCA occlusion, cognitive impairment, and decreased CVR, we examined cognition, CVR, leukoaraiosis grades, and blood data. Data from 15 patients who underwent anastomosis were compared to that in 15 patients who did not undergo anastomosis, and to bilateral data already reported on 65 patients with severe steno-occlusive disease., Results: Cerebral blood flow, CVR, and cognition improved after anastomosis compared to before, and compared to patients without anastomosis; improved values were maintained for 5years. CVR recovered after anastomosis, matching the linear relationship between ipsilateral and contralateral CVR seen in the 65 patients., Conclusion: The postoperative improvement in cognition and synchronized recovery on the regression line between CVR of the ipsilateral occlusion and contralateral sides may suggest that the CVR is widespread and nonselectively related to cognitive function., (Copyright © 2017 Elsevier B.V. All rights reserved.)
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- 2017
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18. Ultrasonography Monitoring with Superb Microvascular Imaging Technique in Brain Tumor Surgery.
- Author
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Ishikawa M, Ota Y, Nagai M, Kusaka G, Tanaka Y, and Naritaka H
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- Adult, Aged, Female, Humans, Male, Middle Aged, Neuronavigation methods, Neurosurgical Procedures methods, Brain Neoplasms diagnostic imaging, Brain Neoplasms surgery, Microvessels diagnostic imaging, Microvessels surgery, Monitoring, Intraoperative methods, Ultrasonography, Interventional methods
- Abstract
Background: Neuronavigation based on preoperative magnetic resonance imaging has been developed as a useful tool to improve visibility of the surgical site in the operative field. Ultrasonography (US) monitoring has also been used as a reliable imaging technique, providing real-time information during neurosurgical operations. We combined the latest innovative imaging technique for detecting very low-flow components, Superb Microvascular Imaging (SMI), with US monitoring during brain tumor surgery., Case Description: Fifteen patients diagnosed with brain tumor (8 malignant and 7 benign) underwent neurosurgery with US monitoring using an Aplio 400/500 US system with the new SMI technique (imaging frequency, 10-12 MHz; frame rate, 28-31 Hz). Features of the SMI images in the gray scale mode include 1) visualization of low-velocity flow with minimal motion artifact, 2) high resolution of images, and 3) high frame rates. The tumors, tumor vessels, compressed and shifted healthy vessels, and cistern were clearly visualized on the SMI images in the gray scale mode, detailing the characteristics of healthy brain tissue (vertically penetrating, fine, straight vessels), glioblastoma (rounding, dilating, and bending vessels), low-grade glioma (fine and straight vessels), meningioma (many large and branching vessels), and lymphoma (less vascular, low echoic tumor) and demonstrating the tumor-defined border. We also performed biopsies under US monitoring with SMI., Conclusions: We combined SMI technique with US monitoring during brain tumor surgery and observed healthy and tumor vessels. Further research is important for the development of a more precise and reliable neurosurgery., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
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19. Collateral Flow and White Matter Disease in Patients with Internal Carotid Artery Occlusion.
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Ishikawa M, Sugawara H, Nagai M, Kusaka G, Tanaka Y, and Naritaka H
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- Adult, Aged, Carotid Artery, Internal pathology, Cerebrovascular Circulation physiology, Female, Humans, Leukoencephalopathies etiology, Magnetic Resonance Angiography, Magnetic Resonance Imaging, Male, Middle Aged, Carotid Stenosis complications, Cerebral Infarction pathology, Collateral Circulation physiology, Leukoencephalopathies pathology
- Abstract
Background: When an internal carotid artery (ICA) occludes, a patient may develop cerebral infarction (CI). We investigated whether CI caused by ICA occlusion (ICAO) is associated with collateral flow through the anterior and posterior communicating arteries (ACoA and PCoA)., Methods: In 100 patients with ICAO, we investigated CI and white matter disease by performing an MRI and the anatomy of the ACoA and PCoA were investigated by performing magnetic resonance angiography. All patients were divided into the symptomatic CI group or the no-CI group. The collateral flow pathway was estimated by the anterior cerebral artery (ACA)-PCoA score and the collateral flow volume after ICAO was estimated by the middle cerebral artery (MCA) flow score, based on how well the MCA was visualized., Results: Of 100 patients with ICAO, the symptomatic CI group included 36 patients. ACA-PCoA score and white matter disease grades were significantly higher in the CI group (indicating poor collateral flow). More than 80% of patients with an ACA-PCoA score of 4 (poor collateral) experienced symptomatic CI. Thirty-one symptomatic CI patients (86%) had an MCA flow score of 1 or 2 (decreased MCA flow)., Conclusion: The ACA-PCoA score and white matter disease grade may suggest an increased risk of CI following ICAO., (© 2016 S. Karger AG, Basel.)
- Published
- 2017
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20. Cortical microcirculatory disturbance in the super acute phase of subarachnoid hemorrhage - In vivo analysis using two-photon laser scanning microscopy.
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Ishikawa M, Kajimura M, Morikawa T, Tsukada K, Tsuji T, Kusaka G, Tanaka Y, and Suematsu M
- Subjects
- Analysis of Variance, Animals, Astrocytes metabolism, Cerebral Cortex diagnostic imaging, Cerebral Cortex pathology, Disease Models, Animal, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Imaging, Three-Dimensional, Male, Mice, Mice, Transgenic, Microscopy, Confocal, Subarachnoid Hemorrhage diagnostic imaging, Time Factors, Cerebral Cortex blood supply, Cerebrovascular Circulation physiology, Microcirculation, Subarachnoid Hemorrhage pathology
- Abstract
Objective: Subarachnoid hemorrhage (SAH) causes cerebral ischemia and drastically worsens the clinical status at onset. However, the arterial flow is surprisingly well maintained on the cerebral surface. We investigated cortical microcirculatory changes in the super acute phase of SAH using two-photon laser scanning microscopy (TPLSM)., Methods: SAH was induced at the skull base in 10 mice using a prone endovascular perforation model. Before SAH, and 1, 2, 5, 10, 20, 30 and 60min after SAH, the cortical microcirculation was observed with TPLSM through a cranial window. Diameters of penetrating and precapillary arterioles were measured and red blood cell (RBC) velocities in precapillary arterioles were analyzed using a line-scan method after administration of Q-dot 655 nanocrystals., Results: One minute after SAH, RBC velocity and flow in precapillary arterioles drastically decreased to <20% of the pre-SAH values, while penetrating and precapillary arterioles dilated significantly. Subsequently, the arterioles either dilated or constricted inconsistently for 60min with continual decreases in RBC velocity and flow in the arterioles, suggesting neurovascular dysfunction., Conclusion: SAH caused sudden worsening of the cortical arteriolar velocity and flow at onset. The neurovascular unit cannot function sufficiently to maintain cortical microcirculatory flow in the super acute phase of SAH., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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21. Leukocyte plugging and cortical capillary flow after subarachnoid hemorrhage.
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Ishikawa M, Kajimura M, Morikawa T, Tsukada K, Tsuji T, Kusaka G, Tanaka Y, and Suematsu M
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- Animals, Blood Flow Velocity, Male, Mice, Subarachnoid Hemorrhage blood, Cerebrovascular Circulation, Leukocytes pathology, Microcirculation, Subarachnoid Hemorrhage physiopathology
- Abstract
Background: It is believed that increased intracranial pressure immediately after subarachnoid hemorrhage (SAH) causes extensive brain ischemia and results in worsening clinical status. Arterial flow to the cerebral surfaces is clinically well maintained during clipping surgery regardless of the severity of the World Federation of Neurological Societies grade after SAH. To explore what kinds of changes occur in the cortical microcirculation, not at the cerebral surface, we examined cortical microcirculation after SAH using two-photon laser scanning microscopy (TPLSM)., Methods: SAH was induced in mice with an endovascular perforation model. Following continuous injection of rhodamine 6G, velocities of labeled platelets and leukocytes and unlabeled red blood cells (RBCs) were measured in the cortical capillaries 60 min after SAH with a line-scan method using TPLSM, and the data were compared to a sham group and P-selectin monoclonal antibody-treated group., Results: Velocities of leukocytes, platelets, and RBCs in capillaries decreased significantly 60 min after SAH. Rolling and adherent leukocytes suddenly prevented other blood cells from flowing in the capillaries. Flowing blood cells also decreased significantly in each capillary after SAH. This no-reflow phenomenon induced by plugging leukocytes was often observed in the SAH group but not in the sham group. The decreased velocities of blood cells were reversed by pretreatment with the monoclonal antibody of P-selection, an adhesion molecule expressed on the surfaces of both endothelial cells and platelets., Conclusions: SAH caused sudden worsening of cortical microcirculation at the onset. Leukocyte plugging in capillaries is one of the reasons why cortical microcirculation is aggravated after SAH.
- Published
- 2016
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22. Role of nitric oxide in the pathogenesis of Barrett's-associated carcinogenesis.
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Kusaka G, Uno K, Iijima K, and Shimosegawa T
- Abstract
Barrett's esophagus (BE), a premalignant condition to Barrett's adenocarcinoma (BAC), is closely associated with chronic inflammation due to gastro-esophageal reflux. Caudal type homeobox 2 (CDX2), a representative marker of BE, is increased during the metaplastic and neoplastic transformation of BE. Nitric oxide (NO) has been proposed to be a crucial mediator of Barrett's carcinogenesis. We previously demonstrated that CDX2 might be induced directly under stimulation of large amounts of NO generated around the gastro-esophageal junction (GEJ) by activating epithelial growth factor receptor in a ligand-independent manner. Thus, we reviewed recent developments on the role of NO in Barrett's carcinogenesis. Notably, recent studies have reported that microbial communities in the distal esophagus are significantly different among groups with a normal esophagus, reflux esophagitis, BE or BAC, despite there being no difference in the bacterial quantity. Considering that microorganism components can be one of the major sources of large amounts of NO, these studies suggest that the bacterial composition in the distal esophagus might play an important role in regulating NO production during the carcinogenic process. Controlling an inflammatory reaction due to gastro-esophageal reflux or bacterial composition around the GEJ might help prevent the progression of Barrett's carcinogenesis by inhibiting NO production.
- Published
- 2016
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23. Cognitive impairment and neurovascular function in patients with severe steno-occlusive disease of a main cerebral artery.
- Author
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Ishikawa M, Saito H, Yamaguro T, Ikoda M, Ebihara A, Kusaka G, and Tanaka Y
- Subjects
- Aged, Arterial Occlusive Diseases physiopathology, Arterial Occlusive Diseases psychology, Carotid Artery, Internal physiopathology, Cerebral Arterial Diseases physiopathology, Cerebral Arterial Diseases psychology, Cerebrovascular Circulation physiology, Cognition Disorders physiopathology, Cognition Disorders psychology, Female, Humans, Male, Middle Aged, Middle Cerebral Artery physiopathology, Neuropsychological Tests, Arterial Occlusive Diseases complications, Cerebral Arterial Diseases complications, Cognition Disorders etiology
- Abstract
Objective: Patients with severe steno-occlusive disease of a main cerebral artery may demonstrate cognitive impairment without identification of causative lesions on magnetic resonance imaging. We investigated whether cognitive impairment in these patients is associated with regional cerebral blood flow (rCBF), leukoaraiosis, risk factors of atherosclerosis and cerebrovascular reserve (CVR), which shows so-called clinical neurovascular function., Methods: In 65 patients with severe steno-occlusive disease of an internal carotid artery or a middle cerebral artery (MCA) and no cerebral infarction (CI), we examined cognitive function with COGNISTAT, grades of leukoaraiosis, and CBF and CVR as calculated by iodine-123-N-isopropyl-p-iodoamphetamine single photon emission computed tomography and blood data. We compared such values of the left and right sided diseases. rCBF and CVR on the affected side were compared to other side., Results: Logistic regression analysis revealed that CVR correlated with cognitive impairment. There was no significant difference in rCBF, CVR, or COGNISTAT score when comparing the left and right sided diseases. There were good correlations between CBF or CVR of the ipsilateral MCA area and ipsilateral and contralateral other areas., Conclusion: Cognitive impairment is associated with CVR in the whole brain. Nonselective widespread neurovascular mild dysfunction can be a reason for cognitive impairment in patients with severe steno-occlusive disease of a main cerebral artery and no CI., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2016
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24. G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer?
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Kanazawa T, Misawa K, Misawa Y, Uehara T, Fukushima H, Kusaka G, Maruta M, and Carey TE
- Subjects
- Galanin metabolism, Head and Neck Neoplasms metabolism, Humans, Somatostatin metabolism, Tachykinins metabolism, Head and Neck Neoplasms drug therapy, Receptors, G-Protein-Coupled metabolism
- Abstract
Therapeutic outcome in head and neck squamous cell carcinoma (HNSCC) is poor in most advanced cases. To improve therapeutic efficiency, novel therapeutic targets and prognostic factors must be discovered. Our studies have identified several G protein-coupled receptors (GPCRs) as promising candidates. Significant epigenetic silencing of GPCR expression occurs in HNSCC compared with normal tissue, and is significantly correlated with clinical behavior. Together with the finding that GPCR activity can suppress tumor cell growth, this indicates that GPCR expression has potential utility as a prognostic factor. In this review, we discuss the roles that galanin receptor type 1 (GALR1) and type 2 (GALR2), tachykinin receptor type 1 (TACR1), and somatostatin receptor type 1 (SST1) play in HNSCC. GALR1 inhibits proliferation of HNSCC cells though ERK1/2-mediated effects on cell cycle control proteins such as p27, p57, and cyclin D1, whereas GALR2 inhibits cell proliferation and induces apoptosis in HNSCC cells. Hypermethylation of GALR1, GALR2, TACR1, and SST1 is associated with significantly reduced disease-free survival and a higher recurrence rate. Although their overall activities varies, each of these GPCRs has value as both a prognostic factor and a therapeutic target. These data indicate that further study of GPCRs is a promising strategy that will enrich pharmacogenomics and prognostic research in HNSCC.
- Published
- 2015
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25. Prospective analysis of risk for bleeding after endoscopic biopsy without cessation of antithrombotics in Japan.
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Ara N, Iijima K, Maejima R, Kondo Y, Kusaka G, Hatta W, Uno K, Asano N, Koike T, Imatani A, and Shimosegawa T
- Subjects
- Aged, Aged, 80 and over, Female, Gastrointestinal Neoplasms complications, Humans, Incidence, Japan, Male, Middle Aged, Prospective Studies, Risk Assessment, Endoscopy, Gastrointestinal adverse effects, Fibrinolytic Agents therapeutic use, Gastrointestinal Hemorrhage epidemiology, Gastrointestinal Neoplasms pathology, Postoperative Hemorrhage epidemiology
- Abstract
Background and Aim: In Japan, after the revision of the gastrointestinal endoscopic guidelines for patients taking antithrombotics, endoscopic biopsies were permitted while continuing antithrombotic treatment. However, the risk of bleeding after the biopsy with or without cessation of antithrombotics has not been fully evaluated because bleeding events are very rare. The aim of this prospective study was to evaluate the risk for bleeding after upper gastrointestinal biopsy without cessation of antithrombotics., Methods: Consecutive patients who underwent upper gastrointestinal endoscopic biopsy from December 2011 to March 2014 were enrolled in this study. Antithrombotic medication and its cessation status was checked at enrollment. To confirm bleeding events associated with biopsy, medical examination at the hospital or direct confirmation by telephone was done within 1 month after the biopsy., Results: Among the 3758 patients who underwent endoscopic biopsies, 394 patients (10.5%) were medicated with antithrombotics, and 286 of them (72.6% of the total antithrombotics users) did not undergo cessation. Bleeding after the biopsy occurred in six cases (0.15%, 95% CI; 0.09%∼0.22%), but there was only one case that had continued taking antithrombotics. The incidence of bleeding after biopsy was not significantly higher in the patients who had continued taking antithrombotics compared with the others (0.35% vs 0.14%, P = 0.38)., Conclusion: This prospective study showed that continuation of antithrombotics did not increase the bleeding risk after upper gastrointestinal endoscopic biopsy., (© 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.)
- Published
- 2015
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26. A case of solitary fibrous tumor arising from the palatine tonsil.
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Kanazawa T, Kodama K, Nokubi M, Gotsu K, Shinnabe A, Hasegawa M, Kusaka G, and Iino Y
- Subjects
- Antigens, CD34 analysis, Female, Humans, Immunohistochemistry, Magnetic Resonance Imaging, Middle Aged, Palatine Tonsil surgery, Proto-Oncogene Proteins c-bcl-2 analysis, Solitary Fibrous Tumors surgery, Tonsillar Neoplasms surgery, Palatine Tonsil pathology, Solitary Fibrous Tumors pathology, Tonsillar Neoplasms pathology
- Abstract
Solitary fibrous tumor (SFT) is a distinctive, relatively uncommon soft-tissue neoplasm that usually arises from the pleura. It occurs at various sites; head and neck lesions are very rare. While most of these tumors have a benign course, a small number have malignant potential. We describe a rare case of SFT arising from the left palatine tonsil in a 66-year-old Japanese woman. The mass was completely resected. Immunohistochemical studies were strongly positive for CD34 and bcl-2, mildly positive for phosphorylated protein kinase B and phosphorylated extracellular signal-regulated kinase 1/2, and negative for platelet-derived growth factor receptor alpha and p53. These findings suggested that this tumor was benign. The patient showed no evidence of recurrence during 2 years of follow-up. We believe that the candidate prognostic marker should be checked to distinguish malignant from benign SFTs.
- Published
- 2015
27. Early diagnosis of cerebral ischemia in cerebral vasospasm by oxygen-pulse near-infrared optical topography.
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Tanaka Y, Ebihara A, Ikota M, Yamaguro T, Kamochi H, Kusaka G, Ishikawa M, Konno T, Mashiko T, and Watanabe E
- Subjects
- Adult, Aged, Early Diagnosis, Female, Humans, Iodine Radioisotopes, Male, Middle Aged, Oxygen blood, Retrospective Studies, Tomography, Emission-Computed, Single-Photon, Young Adult, Brain Ischemia diagnosis, Brain Ischemia etiology, Brain Ischemia metabolism, Oximetry methods, Spectroscopy, Near-Infrared methods, Subarachnoid Hemorrhage complications, Subarachnoid Hemorrhage metabolism, Vasospasm, Intracranial diagnosis, Vasospasm, Intracranial etiology, Vasospasm, Intracranial metabolism
- Abstract
Purpose: Early diagnosis of vasospasm is a key factor in the choice of treatment after subarachnoid hemorrhage (SAH). However, a noninvasive method of diagnosing delayed ischemic neurological deficit (DIND) has not been established. We therefore propose a new method of diagnosing cerebral ischemia using near-infrared optical topography (OT) with oxygen inhalation., Materials and Methods: We used a 44-channel OT system that covers the bilateral front otemporoparietal areas to assess 29 patients who underwent surgery within 72 h of the onset of SAH. The patients inhaled room air followed by oxygen for 2 min, and then peripheral oxygen saturation (SpO₂) was continuously monitored at the index fingertip. The patients were assessed by N-isopropyl-p-[¹²³I]iodoamphetamine (IMP)-SPECT and OT on the same day. Ischemic findings were confirmed using principal component analysis with reference to the systemic SpO₂value., Results: Seven of 29 patients developed DIND. Evidence of ischemia was identified by OT in all seven of these patients before the onset of DIND. The OT and SPECT findings agreed in 27 (93 %) of the 29 patients., Discussion and Conclusions: Our method might detect cerebral ischemia before the onset of DIND and thus be clinically useful for assessing cerebral ischemia with vasospasm.
- Published
- 2015
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28. Late onset cerebrospinal fluid leakage associated with past head injury.
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Kamochi H, Kusaka G, Ishikawa M, Ishikawa S, and Tanaka Y
- Subjects
- Aged, Cerebrospinal Fluid Otorrhea diagnosis, Cerebrospinal Fluid Otorrhea surgery, Cerebrospinal Fluid Rhinorrhea diagnosis, Cerebrospinal Fluid Rhinorrhea surgery, Craniocerebral Trauma diagnosis, Craniotomy, Ethmoid Bone injuries, Ethmoid Bone surgery, Female, Follow-Up Studies, Humans, Male, Meningitis etiology, Meningitis surgery, Middle Aged, Occipital Bone injuries, Occipital Bone surgery, Occupational Injuries diagnosis, Petrous Bone injuries, Petrous Bone surgery, Postoperative Complications diagnosis, Reoperation, Skull Fractures complications, Skull Fractures diagnosis, Skull Fractures surgery, Surgical Flaps surgery, Tomography, X-Ray Computed, Cerebrospinal Fluid Otorrhea etiology, Cerebrospinal Fluid Rhinorrhea etiology, Craniocerebral Trauma complications, Craniocerebral Trauma surgery, Occupational Injuries surgery, Postoperative Complications surgery
- Abstract
Late onset cerebrospinal fluid (CSF) leakage, such as rhinorrhea or otorrhea, is a rare complication of closed head injury. We encountered two cases of delayed CSF leakage more than 10 years after head injury. In both cases, surgical treatments were performed using intradural approaches, and the dural defects were closed with viable pedicled flaps. After surgery, the CSF leakage was completely cured and no remarkable complication was observed in either case. The present two cases of late onset CSF leakage suggest that surgical repair procedures should be performed as soon as the leaks are discovered. A bifrontal intracranial approach is recommended to treat frontal cranial base leakage. Temporal craniotomy is recommended to treat temporal base leakage. All cases should be treated using an intradural approach, and the dural defect is best repaired with viable pedicled flaps.
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- 2013
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29. The role of nitric oxide in the induction of caudal-type homeobox 2 through epidermal growth factor receptor in the development of Barrett's esophagus.
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Kusaka G, Uno K, Iijima K, Endo H, Asano N, Koike T, Imatani A, and Shimosegawa T
- Subjects
- CDX2 Transcription Factor, Carcinoma, Squamous Cell metabolism, Cell Line, Tumor, Epithelium metabolism, Epithelium pathology, Humans, Immunohistochemistry, Phosphorylation, Tyrosine analogs & derivatives, Tyrosine metabolism, Barrett Esophagus metabolism, Barrett Esophagus pathology, ErbB Receptors metabolism, Esophagogastric Junction metabolism, Esophagogastric Junction pathology, Homeodomain Proteins metabolism, Metaplasia metabolism, Metaplasia pathology, Nitric Oxide metabolism
- Abstract
Objective: The high concentration of nitric oxide (NO) around the gastro-esophageal junction (GEJ) might play an important role in the development of Barrett's esophagus (BE), a precursor of Barrett's adenocarcimona. Although previous studies revealed that the expression of caudal-type homeobox 2 (CDX2), an important marker of BE, might be induced through Epidermal Growth Factor Receptor (EGFR), the roles of NO in this signal transduction remain unclear., Material and Methods: First, we investigated the expressions of EGFR, CDX2 and nitrotyrosine by immunohistochemical study for BE and squamous epithelium of human specimens. Second, we studied the effect of peroxynitrite, peroxynitrite stimulator, SIN-1, or NO donor, NOC7, on the expression of phosphorylated EGFR and CDX2 in KYSE30, an EGFR-rich human esophageal squamous cell carcinoma cell-line. Specific inhibitors for EGFR, AG1478 and small interfering RNA for EGFR (EGFR-siRNA) were employed to elucidate the role of EGFR in the induction of CDX2., Results: The immunohistochemical study revealed that the expressions of EGFR, CDX2 and nitrotyrosine in BE were stronger than those in squamous epithelium with positive correlations. Exposure to peroxynitrite, SIN-1 or NOC7 induced EGFR phosphorylation and CDX2 expression in dose- and time-dependent manners. Both EGFR phosphorylation and CDX2 induction were significantly diminished by AG 1478 and EGFR-siRNA., Conclusions: We revealed for the first time that extrinsic NO might directly induce CDX2 expression through EGFR phosphorylation. We suggested that NO had an important role in the development of BE from squamous epithelium around GEJ.
- Published
- 2012
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30. Direct measurement of gastroesophageal reflux episodes in patients with squamous cell carcinoma by 24-h pH-impedance monitoring.
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Uno K, Iijima K, Hatta W, Koike T, Abe Y, Asano N, Kusaka G, and Shimosegawa T
- Subjects
- Aged, Aged, 80 and over, Carcinoma, Squamous Cell physiopathology, Electric Impedance, Esophageal Neoplasms physiopathology, Gastric Acid chemistry, Gastric Acidity Determination, Gastritis, Atrophic complications, Gastroesophageal Reflux complications, Humans, Hydrogen-Ion Concentration, Male, Middle Aged, Monitoring, Physiologic, Statistics, Nonparametric, Carcinoma, Squamous Cell etiology, Esophageal Neoplasms etiology, Gastritis, Atrophic physiopathology, Gastroesophageal Reflux physiopathology
- Abstract
Objectives: Recent studies have consistently reported a significant association between gastric atrophy and esophageal squamous cell carcinomas (ESCCs). However, causative factors responsible for the linkage remain to be clarified. Multichannel intraluminal impedance monitoring in conjunction with a pH sensor (MII-pH) is a reliable technique to evaluate gastroesophageal reflux (GER) episodes, independent of the acidity. We investigated the potential roles of GER in the pathogenesis of ESCC with MII-pH., Methods: From August 2008 to May 2010, 14 consecutive inpatients with superficial ESCCs (ESCC group) and 14 age- and sex-matched inpatients without any esophageal dysplastic lesions (non-ESCC group) were enrolled. Twenty-four hour portable MII-pH monitoring was performed under standard hospitalized conditions. The data of MII-pH were used to identify acid reflux (AR: pH drop below 4.0 during a reflux episode) and non-AR (NAR: pH drop above 4.0 during a reflux episode)., Results: The median intragastric pH of the ESCC group was 4.7 (2.3-6.4), implying hypochlorhydria in this patient group. The numbers of total reflux and NAR episodes in the ESCC group were significantly higher than those in the non-ESCC group (56 (43-87) vs. 35.5 (18-47), P=0.016 for total reflux and 46.5 (32-84) vs. 24.5 (8-37), P=0.012 for NAR), whereas the numbers of AR were similar in both groups. In addition, there was significance in the category of percentage time of bolus reflux episodes., Conclusions: Using MII-pH monitoring, we revealed the clinical significance of GER, especially NAR, in ESCCs. NAR may be a key factor in the link between gastric atrophy and ESCCs.
- Published
- 2011
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31. The balance between 4-hydroxynonenal and intrinsic glutathione/glutathione S-transferase A4 system may be critical for the epidermal growth factor receptor phosphorylation of human esophageal squamous cell carcinomas.
- Author
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Uno K, Kato K, Kusaka G, Asano N, Iijima K, and Shimosegawa T
- Subjects
- Acetylcysteine pharmacology, Aged, Aldehydes chemistry, Aldehydes pharmacology, Antimetabolites pharmacology, Blotting, Western, Buthionine Sulfoximine pharmacology, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Cell Line, Tumor, ErbB Receptors antagonists & inhibitors, Esophageal Neoplasms genetics, Esophageal Neoplasms pathology, Female, Gene Expression Regulation, Neoplastic, Glutathione antagonists & inhibitors, Glutathione Transferase genetics, Humans, Immunohistochemistry, Male, Phosphorylation drug effects, Quinazolines, Reverse Transcriptase Polymerase Chain Reaction, Transfection, Tyrphostins pharmacology, Aldehydes metabolism, Carcinoma, Squamous Cell metabolism, ErbB Receptors metabolism, Esophageal Neoplasms metabolism, Glutathione metabolism, Glutathione Transferase metabolism
- Abstract
Oxidative stress might participate in the carcinogenesis of human esophageal squamous cell carcinomas (hESCC). 4-Hydroxynonenal (HNE) is a major product of membrane lipid peroxidation with short life. It might act as an important mediator through the generation of adducts and activate epidermal growth factor receptor (EGFR) signaling. It is mainly trapped with glutathione (GSH) and catalyzed by glutathione S-transferases (GSTs). This study aimed to elucidate the possible participation of HNE, GSH/GST system, and EGFR signaling in hESCC development. Immunohistochemistry of HNE adducts, EGFR, and phosphorylated EGFR (pEGFR) was performed with hESCC specimens. The effect of HNE on the phosphorylation of EGFR and its downstream PhospholipaseCγ1 (PLCγ1) was investigated with KYSE30 cell-line. Pretreatment with GSH inducer N-acetylcysteine (NAC) or GSH inhibitor Buthionine sulfoximine (BSO) and mandatory transfection of hGSTA4 gene in KYSE30 were conducted to investigate the relationship between HNE and GSH/GST system. Immunoreactants of HNE adducts, EGFR, and pEGFR were increased in hESCC compared to non-cancerous epithelium with positive correlations. The treatment of HNE ligand-independently induced the phosphorylation of EGFR and PLCγ1 accompanying the diminishment of intracellular GSH level. NAC increased GSH contents but BSO decreased in dose-dependent manners. Reflecting changes in GSH, HNE-induced EGFR phosphorylation was suppressed by NAC, whereas it was promoted by BSO. Mandatory expression of hGSTA4 suppressed HNE-induced events. We first demonstrated that the ligand-independent activation of EGFR by the balance between the stimulation of HNE and the prevention of intrinsic GSH/GST system might participate in the development of hESCC., (Copyright © 2011 Wiley-Liss, Inc.)
- Published
- 2011
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32. Current reconstructive techniques following head and neck cancer resection using microvascular surgery.
- Author
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Kanazawa T, Sarukawa S, Fukushima H, Takeoda S, Kusaka G, and Ichimura K
- Abstract
Various techniques have been developed to reconstruct head and neck defects following surgery to restore function and cosmetics. Free tissue transfer using microvascular anastomosis has transformed surgical outcomes and the quality of life for head and neck cancer patients because this technique has made it possible for surgeons to perform more aggressive ablative surgery, but there is room for improvement to achieve a satisfactory survival rate. Reconstruction using the free tissue transfer technique is closely related to cardiovascular surgery because the anastomosis techniques used by head and neck surgeons are based on those of cardiovascular surgeons; thus, suggestions from cardiovascular surgeons might lead to further development of this field. The aim of this article is to present the recent general concepts of reconstruction procedures and our experiences of reconstructive surgeries of the oral cavity, mandible, maxilla, oropharynx and hypopharynx to help cardiovascular surgeons understand the reconstructions and share knowledge among themselves and with neck surgeons to develop future directions in head and neck reconstruction.
- Published
- 2011
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33. Intraoperative monitoring during surgery for hypoglossal schwannoma.
- Author
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Ishikawa M, Kusaka G, Takashima K, Kamochi H, and Shinoda S
- Subjects
- Electromyography, Humans, Male, Middle Aged, Cranial Nerve Neoplasms surgery, Hypoglossal Nerve surgery, Hypoglossal Nerve Diseases surgery, Monitoring, Intraoperative methods, Neurilemmoma surgery
- Abstract
A 54-year-old man presented with an intracranial schwannoma of the hypoglossal nerve between the medulla and the left hypoglossal canal. The condylar fossa approach was used with intra-operative electromyography (EMG) monitoring of the lower cranial nerves. The tumor was then removed carefully without decreasing the tongue EMG responses. EMG monitoring enabled us to remove the tumor while maintaining the function of the hypoglossal nerve. Tongue EMG was easily recorded by stimulating the hypoglossal nerve fibers, which was useful in identifying the hypoglossal nerve and evaluating its function. This suggests that tongue EMG is a useful monitoring tool to enhance neurological outcome following removal of tumors in this region., (Copyright 2009 Elsevier Ltd. All rights reserved.)
- Published
- 2010
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34. Treatment with botulinum toxin improves the hyperexcitability of the facial motoneuron in patients with hemifacial spasm.
- Author
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Ishikawa M, Takashima K, Kamochi H, Kusaka G, Shinoda S, and Watanabe E
- Subjects
- Aged, Aged, 80 and over, Blinking drug effects, Botulinum Toxins, Type A pharmacology, Electric Stimulation methods, Evoked Potentials drug effects, Facial Nerve drug effects, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neuromuscular Agents pharmacology, Time Factors, Botulinum Toxins, Type A therapeutic use, Facial Nerve pathology, Hemifacial Spasm drug therapy, Hemifacial Spasm pathology, Motor Neurons drug effects, Neuromuscular Agents therapeutic use
- Abstract
Botulinum toxin type A (BTX) injection into the orbicularis oculi muscle is an effective treatment for patients with hemifacial spasm (HFS). The objectives of this study were to investigate the effect of this treatment on HFS, in particular the associated hyperexcitability of the facial motor nucleus, and to discuss the potential mechanism of HFS. F waves in the mentalis muscle were examined before, 2 and 6 weeks after the BTX treatment of only the orbicularis oculi muscle in ten patients with HFS. F/M ratio, duration of F waves and frequency of F waves decreased significantly after the BTX treatment compared with those before the BTX treatment. These findings demonstrate that the excitability of the facial motonucleus decreases after BTX treatment of the orbicularis oculi muscle. From these results, we hypothesize that the trigeminal afferent input and the cortical control contribute to the hyperexcitability of the facial motor nucleus in patients with HFS. This warrants further investigation into the pathophysiology of HFS.
- Published
- 2010
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35. Clipping of a vertebral artery aneurysm behind the hypoglossal nerve under the monitoring of lower cranial nerves.
- Author
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Ishikawa M, Kusaka G, Takashima K, Kamochi H, and Shinoda S
- Subjects
- Female, Humans, Hypoglossal Nerve, Intracranial Aneurysm diagnostic imaging, Middle Aged, Subarachnoid Hemorrhage diagnostic imaging, Subarachnoid Hemorrhage pathology, Subarachnoid Hemorrhage surgery, Tomography, X-Ray Computed, Cranial Nerves physiology, Intracranial Aneurysm pathology, Intracranial Aneurysm surgery, Monitoring, Intraoperative, Neurosurgical Procedures instrumentation, Surgical Instruments, Vertebral Artery pathology, Vertebral Artery surgery
- Abstract
Under an operative view, an aneurysm of the vertebral artery is located behind the lower cranial nerves. To prevent neurological deficits we employed electrophysiological monitoring while clipping an aneurysm of the vertebral artery. A 64-year-old woman had suffered a sudden severe headache in the morning. Computed tomography (CT) revealed a subarachnoid hemorrhage (SAH) and CT angiography revealed an aneurysm at a branching point of the left vertebral artery. The condylar fossa approach was taken while recording electromyography (EMG) of the lower cranial nerves. The aneurysm was located just behind the hypoglossal nerve and could not be clipped without strong traction of the hypoglossal nerve. Therefore, the hypoglossal nerve was divided to separate the lower two bundles of the hypoglossal nerve from the other bundles, and the clip was applied to the aneurysm between the nerve bundles without any change of the tongue EMG. The patient went home 10 days after operation with no neurological deficit. In conclusion, we report a case of a ruptured aneurysm of a vertebral artery, which was clipped while monitoring the lower cranial nerves. Tongue EMG monitoring enabled us to clip the aneurysm without nerve injury and revealed that the hypoglossal nerve near the hypoglossal canal can be divided into several bands without neurological deficit., (Copyright 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
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36. Platelet and leukocyte adhesion in the microvasculature at the cerebral surface immediately after subarachnoid hemorrhage.
- Author
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Ishikawa M, Kusaka G, Yamaguchi N, Sekizuka E, Nakadate H, Minamitani H, Shinoda S, and Watanabe E
- Subjects
- Animals, Brain pathology, Male, Mice, Mice, Inbred C57BL, Subarachnoid Hemorrhage pathology, Brain immunology, Cell Adhesion immunology, Cerebrovascular Circulation immunology, Leukocytes immunology, Microcirculation immunology, Microvessels immunology, Platelet Adhesiveness immunology, Subarachnoid Hemorrhage immunology
- Abstract
Objective: Pathophysiology after subarachnoid hemorrhage (SAH) caused by aneurysmal rupture has not been well examined. The purpose of this study was to observe platelet-leukocyte-endothelial cell interactions as indexes of inflammatory and prothrombogenic responses in the acute phase of SAH, using an in vivo cranial window method., Methods: Subarachnoid hemorrhage was induced in C57Bl/6J mice by using the endovascular perforation method. Intravital microscopy was used to monitor the rolling and adhesion of platelets and leukocytes that were labeled with different fluorochromes. Regional cerebral blood flow was measured with laser Doppler flowmetry. The platelet-leukocyte-endothelial cell interactions were observed 30 minutes, 2 hours, and 8 hours after SAH. The effect of P-selectin antibody and apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, on these responses was examined at 2 hours after SAH, and compared with a different SAH model in which autologous blood was injected into the foramen magna., Results: SAH was accompanied by a 60% decrease in regional cerebral blood flow, whereas no changes in regional cerebral blood flow were observed on the contralateral side. SAH elicited time- and size-dependent increases in rolling and adherent platelets and leukocytes in cerebral venules. All of these interactions were attenuated by treatment with a P-selectin antibody or apocynin. There was no significant blood cell recruitment observed in the blood-injected SAH model., Conclusion: SAH at the skull base induced P-selectin- and oxygen radical-mediated platelet-leukocyte-endothelial cell interactions in venules at the cerebral surface. These early inflammatory and prothrombogenic responses may cause a whole-brain injury immediately after SAH.
- Published
- 2009
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37. [Evoked potential monitoring in an operation of neurosurgery].
- Author
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Takashima K, Takahashi M, Yubune N, Inaba N, Omoto K, Kawano M, Sakurabayashi I, Ishikawa M, Kusaka G, and Shinoda S
- Subjects
- Humans, Evoked Potentials, Monitoring, Intraoperative methods, Neurosurgical Procedures
- Abstract
In the neurosurgical field, the evoked potential is employed for the monitoring of intraoperative nerve function. During evoked potential monitoring, surgical manipulation-related nerve dysfunction is detected, and functional localization/nerves in the cerebral cortex are identified to prevent postoperative neurological complications. It is important to reduce the contact resistance to 2 kOmega or less on the application of plate electrodes used for recording and prevent noise by bundling electrode leads, to ensure a stable evoked potential during surgery. In our laboratory, intraoperative monitoring, such as ABR to prevent auditory disturbance, SEP to detect cerebral ischemia, cortical SEP and MEP to prevent motor paralysis, and evoked electromyography to identify/maintain the cranial nerves including the facial, trigeminal, oculomotor, and abducens nerves, is performed based on requests from the Department of Neurosurgery.
- Published
- 2008
38. SIADH is only an atypical clinical feature in a patient with prolactinoma.
- Author
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Saito T, Watanabe Y, Yuzawa M, Saito T, Tamemoto H, Suzuki H, Kusaka G, Omori Y, Shinoda S, Kawakami M, and Ishikawa SE
- Subjects
- Humans, Hyponatremia etiology, Magnetic Resonance Imaging, Male, Middle Aged, Pituitary Neoplasms pathology, Pituitary Neoplasms surgery, Pituitary-Adrenal System physiology, Prolactinoma pathology, Prolactinoma surgery, Inappropriate ADH Syndrome etiology, Pituitary Neoplasms complications, Prolactinoma complications
- Abstract
A 50-year-old man was admitted to determine the pathogenesis of hyponatremia. He had a poor appetite and was easily fatigued. Physical findings showed that he was conscious and alert. He had neither dry skin or tongue, nor pretibial edema. Laboratory data revealed that the serum sodium level was 110 mmol/l; plasma osmolality, 238 mmol/kg; and urinary osmolality, 417 mmol/kg. Plasma arginine vasopressin was 0.5 pg/ml despite plasma osmolality of 242 mmol/kg. An acute water load showed impaired water excretion, as percent excretion of water load was 30% and minimal urinary osmolality was 642 mmol/kg. Serum prolactin was 254 ng/ml, and anterior pituitary hormones of ACTH, TSH and GH were in the normal ranges. Brain magnetic resonance imaging (MRI) showed a pituitary tumor with a size of 20 x 22 x 21 mm and it pushed a pituitary stalk upward. Immunohistochemistry revealed prolactinoma. After the adenomectomy, serum sodium level has been kept normal with free access to water intake. The present study indicates that syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is manifested in association with pituitary macroadenoma of prolactinoma.
- Published
- 2007
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39. Electroconvulsive therapy for seizure control: preliminary data in a new seizure generation and control model.
- Author
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Patwardhan RV, Besio W, Calvert JW, Kusaka G, Kusaka I, Zhang J, and Nanda A
- Subjects
- Age of Onset, Animals, Male, Penicillins, Rats, Rats, Wistar, Seizures chemically induced, Disease Models, Animal, Electroconvulsive Therapy, Seizures therapy
- Abstract
Electroconvulsive therapy (ECT) effect upon seizure cessation was studied in five male Wistar rats using a penicillin intracisternal injection model (which did not damage the cranial vault). Animals were observed both clinically and electrographically for seizure development. ECT was applied at varying times following onset of seizure, at varying parameters (frequency, pulsewidth, and duration). ECT affected EEG seizure pattern in several different stimulation parameter-dependent ways: (1) modulation to different pattern; (2) increased interictal time; and (3) seizure cessation. Stimulation with higher, sustained current (50 mA) led to changes in seizure amplitude; stimulation at pulses of current led to seizure frequency dimunition, and at certain characteristic pulses "capture" was seen as the EEG activity mimicked the ECT-inducing stimulation pattern. Interictal time was usually increased by sustained, continuous (rather than pulsatile) stimulation. Seizure activity was completely stopped in several instances using parameters of 800 pulses at a frequency of 200 Hz, with 2.56 ms pulsewidth and 50 mA of current (in consecutive iterations for one specimen). No ECT-related adverse effects were noted. Analogous to the heart, pacing or defibrillating the brain using external scalp electrodes may have a role in the control of otherwise intractable seizures.
- Published
- 2005
- Full Text
- View/download PDF
40. Technical note: preliminary results in development of a novel intracisternal penicillin seizure model in the rat.
- Author
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Patwardhan RV, Calvert JW, Besio W, Kusaka G, Kusaka I, Zhang J, and Nanda A
- Subjects
- Animals, Injections, Intraperitoneal, Male, Rats, Rats, Wistar, Disease Models, Animal, Epilepsy chemically induced, Penicillins
- Abstract
In order to develop an intracisternal penicillin rat model of epilepsy, eleven anesthetized male Wistar rats were studied. 5 underwent intracisternal injection of penicillin (doses 150,000-300,000 units) in the prone position, and another 5 underwent intraperitoneal penicillin injection; one died following intracisternal injection, prior to further study. Time between penicillin injection and seizure induction (determined by electroencephalography) was recorded. Each animal had a tracheostomy, and was mechanically ventilated and carefully monitored for adverse effects. Seizures were noted in an average of 13:42 minutes following penicillin injection (range 4:30-23:20) for the intracisternally (IC) injected group. Both episodic and continuous seizure activity was seen, and a dose-dependent effect was seen (quicker-onset, more continuous seizures with higher doses, in the IC group). Onset was significantly faster in the IC than for the intraperitoneally injected group (all >1 hour for the latter group in our study). 96 total separate seizure episodes were seen, ranging from 3 to 540 seconds. Epileptic activity could be seen in all IC-injected rats lasting over 1 hour into the study. The intracisternal penicillin injection rat model appears to provide a quick-onset, reliable method of inducing seizure activity in the rat model while leaving the cranial vault intact.
- Published
- 2005
- Full Text
- View/download PDF
41. Signaling pathways for early brain injury after subarachnoid hemorrhage.
- Author
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Kusaka G, Ishikawa M, Nanda A, Granger DN, and Zhang JH
- Subjects
- Animals, Blood-Brain Barrier drug effects, Blood-Brain Barrier pathology, Blotting, Western, Brain Edema etiology, Brain Edema pathology, Brain Injuries complications, Capillary Permeability drug effects, Capillary Permeability physiology, Enzyme Activation drug effects, Enzyme Activation physiology, Enzyme Inhibitors pharmacology, Intracranial Pressure drug effects, Intracranial Pressure physiology, Male, Microscopy, Fluorescence, Mitogen-Activated Protein Kinases biosynthesis, Pyrazoles pharmacology, Pyrimidines pharmacology, Rats, Rats, Sprague-Dawley, Subarachnoid Hemorrhage complications, Vascular Endothelial Growth Factor A biosynthesis, src-Family Kinases biosynthesis, src-Family Kinases drug effects, Brain Injuries physiopathology, Signal Transduction physiology, Subarachnoid Hemorrhage physiopathology
- Abstract
Few studies have examined the signaling pathways that contribute to early brain injury after subarachnoid hemorrhage (SAH). Using a rat SAH model, the authors explored the role of vascular endothelial growth factor (VEGF) and mitogen-activation protein kinase (MAPK) in early brain injury. Male Sprague-Dawley rats (n = 172) weighing 300 to 350 g were used for the experimental SAH model, which was induced by puncturing the bifurcation of the left anterior cerebral and middle cerebral arteries. The blood-brain barrier (BBB), brain edema, intracranial pressure, and mortality were evaluated at 24 hours after SAH. The phosphorylation of VEGF and different MAPK subgroups (ERK1/2, p38, and JNK) were examined in both the cortex and the major cerebral arteries. Experimental SAH increased intracranial pressure, BBB permeability, and brain edema and produced high mortality. SAH induced phosphorylation of VEGF and MAPKs in the cerebral arteries and, to a lesser degree, in the cortex. PP1, an Src-family kinase inhibitor, reduced BBB permeability, brain edema, and mortality and decreased the phosphorylation of VEGF and MAPKs. The authors conclude that VEGF contributes to early brain injury after SAH by enhancing the activation of the MAPK pathways, and that the inhibition of these pathways might offer new treatment strategies for SAH.
- Published
- 2004
- Full Text
- View/download PDF
42. Role of AT1 receptors and NAD(P)H oxidase in diabetes-aggravated ischemic brain injury.
- Author
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Kusaka I, Kusaka G, Zhou C, Ishikawa M, Nanda A, Granger DN, Zhang JH, and Tang J
- Subjects
- Animals, Antihypertensive Agents pharmacology, Benzimidazoles pharmacology, Biphenyl Compounds, Blood Glucose, Blood Pressure, Body Weight, Brain Edema drug therapy, Brain Edema metabolism, Brain Infarction drug therapy, Brain Infarction metabolism, Brain Ischemia drug therapy, Carbon Dioxide blood, Diabetic Angiopathies drug therapy, Disease Models, Animal, Immunohistochemistry, Lipid Peroxidation, Male, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Membrane Transport Proteins genetics, NADPH Dehydrogenase genetics, NADPH Oxidase 2, NADPH Oxidases genetics, NADPH Oxidases metabolism, Oxygen blood, Phosphoproteins genetics, RNA, Messenger analysis, Rats, Rats, Sprague-Dawley, Tetrazoles pharmacology, Brain Ischemia metabolism, Diabetic Angiopathies metabolism, Membrane Transport Proteins metabolism, NADPH Dehydrogenase metabolism, Phosphoproteins metabolism, Receptor, Angiotensin, Type 1 metabolism
- Abstract
The objective of the present study was to examine the role of the angiotensin II type 1 receptor (AT(1)-R) in the diabetes-aggravated oxidative stress and brain injury observed in a rat model of combined diabetes and focal cerebral ischemia. Diabetes was induced by an injection of streptozotoxin (STZ; 55 mg/kg iv) at 8 wk of age. Two weeks after the induction of diabetes, some animals received continuous subcutaneous infusion of the AT(1)-R antagonist candesartan (0.5 mg.kg(-1).day(-1)) for 14 days. Focal cerebral ischemia, induced by middle cerebral artery occlusion/reperfusion (MCAO), was conducted at 4 wk after STZ injection. Male Sprague-Dawley rats (n = 189) were divided into five groups: normal control, diabetes, MCAO, diabetes + MCAO, and diabetes + MCAO + candesartan. The major observations were that 1) MCAO produced typical cerebral infarction and neurological deficits at 24 h that were accompanied by elevation of NAD(P)H oxidase gp91(phox) and p22(phox) mRNAs, and lipid hydroperoxide production in the ipsilateral hemisphere; 2) diabetes enhanced NAD(P)H oxidase gp91(phox) and p22(phox) mRNA expression, potentiated lipid peroxidation, aggravated neurological deficits, and enlarged cerebral infarction; and 3) candesartan reduced the expression of gp91(phox) and p22(phox), decreased lipid peroxidation, lessened cerebral infarction, and improved the neurological outcome. We conclude that diabetes exaggerates the oxidative stress, NAD(P)H oxidase induction, and brain injury induced by focal cerebral ischemia. The diabetes-aggravated brain injury involves AT(1)-Rs. We have shown for the first time that candesartan reduces brain injury in a combined model of diabetes and cerebral ischemia.
- Published
- 2004
- Full Text
- View/download PDF
43. New lumbar method for monitoring cerebrospinal fluid pressure in rats.
- Author
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Kusaka G, Calvert JW, Smelley C, Nanda A, and Zhang JH
- Subjects
- Animals, Catheters, Indwelling supply & distribution, Cerebral Hemorrhage cerebrospinal fluid, Cerebral Hemorrhage physiopathology, Cisterna Magna physiology, Disease Models, Animal, Laminectomy methods, Male, Rats, Rats, Sprague-Dawley, Subarachnoid Hemorrhage cerebrospinal fluid, Subarachnoid Hemorrhage physiopathology, Time Factors, Transducers, Pressure supply & distribution, Cerebrospinal Fluid Pressure physiology, Intracranial Pressure physiology, Monitoring, Physiologic methods
- Abstract
Objective: Monitoring cerebrospinal fluid pressure or intracranial pressure (ICP) is crucial in the study of neurosurgical disorders. In the present study, we report a new lumbar method for monitoring ICP in rats., Methods: A PE10 catheter connected to a pressure transducer was placed into the subarachnoid space of L5 through the duramater after laminectomy to record lumbar cerebrospinal fluid pressure (lumbar-ICP). ICP at the cisterna magna (cisterna-ICP) was recorded simultaneously via a catheter in the subarachnoid space at the cisterna magna. Eighteen anesthetized adult male S-D rats were subjected to baseline recording followed by either experimental subarachnoid hemorrhage (SAH) induced by intravascular puncture method or experimental intracerebral hemorrhage (ICH) induced by blood injection with a stereotaxic system., Results: Baseline lumbar-ICP and cisterna-ICP varied between 6 and 8 mmHg, and respiratory variation could be detected. A similar acute response to SAH was recorded in both the lumbar-ICP and cisterna-ICP in all rats. In rats subjected to SAH, the lumbar catheter continuously and accurately monitored lumbar-ICP, and reliable pressure tracings were obtained for up to 24 h after SAH. However, continued cisterna-ICP monitoring was abandoned in two rats in the cisterna magna method due to obstruction of the catheter by blood clots (hematoma)., Conclusion: This new lumbar-ICP method is simple, safe, easy, and reliable in rats. Continued lumbar-ICP measurements provided monitoring for up to 24 h after experimental manipulation.
- Published
- 2004
- Full Text
- View/download PDF
44. Caspase inhibitors prevent endothelial apoptosis and cerebral vasospasm in dog model of experimental subarachnoid hemorrhage.
- Author
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Zhou C, Yamaguchi M, Kusaka G, Schonholz C, Nanda A, and Zhang JH
- Subjects
- Animals, Basilar Artery drug effects, Basilar Artery enzymology, Basilar Artery pathology, Caspase 3, Caspase 8, Cerebral Angiography, Disease Models, Animal, Dogs, Endothelium, Vascular drug effects, Endothelium, Vascular enzymology, Endothelium, Vascular pathology, Female, Immunohistochemistry, In Situ Nick-End Labeling, Male, Receptors, Tumor Necrosis Factor biosynthesis, Subarachnoid Hemorrhage complications, Subarachnoid Hemorrhage enzymology, Subarachnoid Hemorrhage pathology, Vasospasm, Intracranial enzymology, Vasospasm, Intracranial etiology, Vasospasm, Intracranial pathology, Apoptosis drug effects, Caspase Inhibitors, Enzyme Inhibitors therapeutic use, Subarachnoid Hemorrhage drug therapy, Vasodilator Agents therapeutic use, Vasospasm, Intracranial prevention & control
- Abstract
Apoptosis in the endothelium of major cerebral arteries may play a role in the initiation and maintenance of cerebral vasospasm after subarachnoid hemorrhage (SAH). We tested the therapeutic effect of caspase inhibitors on endothelial apoptosis and on cerebral vasospasm in an established dog double-hemorrhage model. Thirty-one mongrel dogs were divided into five groups: control; SAH; SAH treated with vehicle [DMSO]; SAH treated with Ac-DEVD-CHO [a specific caspase-3 inhibitor]; and SAH treated with Z-VAD-FMK [a broad caspase inhibitor]. The inhibitors (100 microM) were injected into the cisterna magna daily from Day 0 through Day 3. Angiography was performed on Day 0 and Day 7. Histology, TUNEL staining, and immunohistochemistry were conducted on basilar arteries collected on Day 7 after SAH. Positive staining of TUNEL, poly(ADP)-ribose polymerase (PARP), caspase-3, and caspase-8 was observed in the endothelial cells of the spastic arteries. Double fluorescence labeling demonstrated co-localization of TUNEL with caspase-3 and TNFalpha receptor-1 (TNFR1). Ac-DEVD-CHO and Z-VAD-FMK prevented endothelial apoptosis and reduced angiographic vasospasm. The mechanism of apoptosis in endothelial cells involves TNFR1 and the caspase-8 and caspase-3 pathways. Caspase inhibitors may have potential in the treatment of cerebral vasospasm.
- Published
- 2004
- Full Text
- View/download PDF
45. Contribution of Src tyrosine kinase to cerebral vasospasm after subarachnoid hemorrhage.
- Author
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Kusaka G, Kimura H, Kusaka I, Perkins E, Nanda A, and Zhang JH
- Subjects
- Animals, Anthraquinones pharmacology, Anthraquinones therapeutic use, Blotting, Western, Cerebral Angiography, Disease Models, Animal, Dogs, Female, Male, Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors, Mitogen-Activated Protein Kinase Kinases metabolism, Muscle Contraction drug effects, Muscle, Smooth drug effects, Pyrimidines pharmacology, Pyrimidines therapeutic use, Subarachnoid Hemorrhage diagnostic imaging, Time Factors, Vasospasm, Intracranial drug therapy, src-Family Kinases antagonists & inhibitors, Subarachnoid Hemorrhage complications, Vasospasm, Intracranial enzymology, Vasospasm, Intracranial etiology, src-Family Kinases metabolism
- Abstract
Object: Mitogen-activated protein kinase (MAPK) has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was conducted to investigate whether Src tyrosine kinase, an upstream regulator of MAPK, is involved in cerebral vasospasm., Methods: An established canine double-hemorrhage model was used. Twenty-four dogs were divided into four groups: control, vehicle-treated, Src inhibitor PP2-treated, and Src inhibitor damnacanthal-treated groups. Vehicle (dimethyl sulfoxide), PP2, or damnacanthal was injected daily into the cisterna magna of 18 dogs at 3 to 6 days after induction of SAH. Angiography was performed on Day 0 (the day on which the first blood injection was administered to induce SAH) and on Day 7. Western blot analysis of Src and MAPK activation in basilar arteries (BAs) collected on Day 7 post-SAH was performed. Severe vasospasm was observed in the BAs of vehicle-treated dogs. Mild vasospasm was observed in all dogs treated with Src inhibitors. Phosphorylated Src and MAPK were increased after SAH and activation of these kinases in the BAs was abolished by PP2 and damnacanthal., Conclusions: The tyrosine kinase Src is an important upstream regulator of MAPK, and inhibition of Src might offer a new therapy in the management of cerebral vasospasm.
- Published
- 2003
- Full Text
- View/download PDF
46. Neurogenic pulmonary edema and large negative T waves associated with subarachnoid hemorrhage.
- Author
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Takahashi M, Mitsuhashi T, Katsuki T, Ikeda U, Tanaka H, Kusaka G, Aoki T, and Shimada K
- Subjects
- Aged, Diagnosis, Differential, Electrocardiography, Female, Humans, Pulmonary Edema physiopathology, Subarachnoid Hemorrhage physiopathology, Tomography, X-Ray Computed, Pulmonary Edema etiology, Subarachnoid Hemorrhage complications, Subarachnoid Hemorrhage diagnosis
- Abstract
We describe a 72-year-old woman with hypertension who developed acute neurogenic pulmonary edema and giant negative T waves on electrocardiography (ECG) due to subarachnoid hemorrhage. The patient was alert and complained of precordial chest discomfort, dyspnea and shoulder stiffness. Echocardiography demonstrated normal left ventricle contraction with hypertrophy. Computed tomography (CT) and subsequent cerebral angiography revealed subarachnoid hemorrhage and saccular aneurysm at the anterior communicating artery. It is important to consider the possibility of subarachnoid hemorrhage when a patient shows pulmonary edema and ECG abnormalities even without typical clinical signs of subarachnoid hemorrhage.
- Published
- 2001
- Full Text
- View/download PDF
47. Chronic hypernatremia derived from hypothalamic dysfunction: impaired secretion of arginine vasopressin and enhanced renal water handling.
- Author
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Fukagawa A, Ishikawa SE, Saito T, Kusaka I, Nakamura T, Higashiyama M, Nagasaka S, Kusaka G, Masuzawa T, and Saito T
- Subjects
- Adult, Aquaporin 2, Aquaporin 6, Aquaporins urine, Blood, Chronic Disease, Diabetes Insipidus diagnosis, Diabetes Insipidus physiopathology, Diuresis, Female, Humans, Hydrocephalus, Normal Pressure complications, Hydrocephalus, Normal Pressure surgery, Magnetic Resonance Imaging, Meningitis complications, Osmolar Concentration, Saline Solution, Hypertonic administration & dosage, Thirst, Urine, Ventriculoperitoneal Shunt, Water, Arginine Vasopressin metabolism, Body Water metabolism, Diabetes Insipidus complications, Hypernatremia etiology, Hypothalamus physiopathology, Kidney metabolism
- Abstract
We analyzed the disorder of water metabolism in a 32 year-old female with chronic hypernatremia. She had meningitis at 4 years, and ventriculo-peritoneal shunt operation at 13 years because of normal pressure hydrocephalus. At 14 years hypernatremia of 166 mmol/l was initially found and thereafter hypernatremia ranging from 150 to 166 mmol/l has been persisted for the last 18 years. Physical and laboratory findings did not show dehydration. Urine volume was 750-1700 ml per day and urinary osmolality (Uosm) 446-984 mmol/kg, suggesting no urinary concentrating defect. Plasma arginine vasopressin (AVP) levels ranged from 0.4 to 1.2 pmol/l despite hyperosmolality of 298 through 343 mmol/kg under ad libitum water drinking. There was no correlation between plasma osmolality (Posm) and plasma AVP levels, but Uosm had a positive correlation with Posm (r=0.545, P < 0.05). Hypertonic saline (500 NaCl) infusion after a water load increased Uosm from 377 to 679 mmol/kg, and plasma AVP from 0.2 to 1.3 pmol/l. There was a positive correlation between Posm and plasma AVP levels in the hypertonic saline test (r=0.612, P<0.05). In contrast, an acute water load (20 ml/kg BW) verified the presence of impaired water excretion, as the percent excretion of the water load was only 8.5% and the minimal Uosm was as high as 710 mmol/kg. Urinary excretion of aquaporin-2 remained low in concert with plasma AVP levels. No abnormality in pituitary-adrenocortical function was found. These results indicate that marked hypernatremia is derived from partial central diabetes insipidus and elevated threshold of thirst, and that enhanced renal water handling may contribute to maintenance of body water in the present subject.
- Published
- 2001
- Full Text
- View/download PDF
48. [A case of alveolar soft-part sarcoma with cerebral metastases].
- Author
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Haga Y, Kusaka G, Mori S, Shinoda S, and Masuzawa T
- Subjects
- Adult, Bone Neoplasms metabolism, Brain Neoplasms diagnosis, Brain Neoplasms therapy, Combined Modality Therapy, Humans, Lung Neoplasms secondary, Magnetic Resonance Imaging, Male, Radiotherapy, Adjuvant, Sarcoma, Alveolar Soft Part diagnosis, Sarcoma, Alveolar Soft Part therapy, Tomography, X-Ray Computed, Brain Neoplasms secondary, Sarcoma, Alveolar Soft Part secondary
- Abstract
A case of alveolar soft-part sarcoma with multiple cerebral metastases in addition to multiple lung and bone metastases is reported. This is a rare tumor which thus far has only been recognized as a malignant soft tissue tumor with great uncertainty. A 24-year-old man with a chief complaint of left frontal headache was admitted to our unit on September 26, 1994. A tumor of the right forearm had been surgically removed 9 years previously, and surgery had been followed by two courses of chemotherapy with vincristine, cyclophosphamide and actinomycin-D and subsequent irradiation for bone metastasis. The chemotherapy, however, did not have any clear effect. Neurological examination at the time revealed only bilateral papilledema, but CT and MRI scan of the brain showed a round mass in the left occipital lobe with homogeneous enhancement and another small mass was detected in the right occipital lobe. A cerebral angiogram showed a vascular tumor. The preoperative diagnosis was multiple cerebral metastases of alveolar soft part sarcoma. Left occipital craniotomy was performed on October 12, 1994, and the tumor was completely removed by lobectomy. Specimens of the tumor showed typical histological features of alveolar soft-part sarcoma. Whole-brain radiotherapy was administered postoperatively, and the patient is well neurologically without right homonymous hemianopsia. The clinical features of alveolar soft-part sarcoma are discussed. Only a few cases have been reported in the literature, but the most frequent site of the primary lesion has been the lower extremities, and cerebral metastasis has not been rare. All efforts should be focused on discovering this tumor in the early stage because surgical removal can yield good results, and radiotherapy is thought to be effective in terms of patient "quality of life".
- Published
- 1996
49. [Rhinogenous retrobulbar optic neuritis: a case report].
- Author
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Kusaka G, Yamada T, Shinoda S, and Masuzawa T
- Subjects
- Adult, Humans, Magnetic Resonance Imaging, Male, Optic Neuritis diagnosis, Optic Neuritis surgery, Tomography, X-Ray Computed, Optic Neuritis etiology, Sinusitis complications
- Abstract
Rhinogenous retrobulbar optic neuritis is characterized by neuritis secondary to paranasal sinusitis. A case of rhinogenous retrobulbar optic neuritis that was successfully treated by surgery is reported. A 40-year-old man complained of progressive right visual disturbance. The clinical course and neurological examination suggested right retrobulbar optic neuritis. CT and MRI scans demonstrated a massive tumor-like lesion near the right optic canal. Fifteen days after the onset, decompression of the right optic nerve was performed using a right pterional approach. After surgery, visual disturbance improved, and after about 1 month, the symptom had disappeared. Operative findings, histological examination and the postoperative course were consistent with the characteristics of rhinogenous retrobulbar optic neuritis. We consider decompression of the optic nerve to be effective for the treatment of rhinogenous retrobulbar optic neuritis.
- Published
- 1994
50. [A cured case of Bochdalek's diaphragmatic hernia].
- Author
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MIYAMOTO S, SEZAI Y, SATO T, ABE S, NEMOTO K, HARADA H, and KUSAKA G
- Subjects
- Humans, Diaphragm, Heart Septal Defects, Heart Septum abnormalities, Hernia, Diaphragmatic, Hernias, Diaphragmatic, Congenital
- Published
- 1961
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