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Biomedical subjects

I Nagata

Publications and source records attributed to I Nagata.

At least 37 records · Page 2Linked to original sources
PubMed2001

Venous congestion is a major cause of neurological deterioration in spinal arteriovenous malformations.

OBJECTIVE: Although venous congestion is considered to be a major cause of progressive myelopathy in patients with spinal dural arteriovenous fistulae (DAVFs), the neurological deterioration in patients with spinal intradural arteriovenous malformations (AVMs) has been attributed to hemorrhage or to vascular steal. To reexamine this theory, we analyzed our own cases of spinal vascular diseases. METHODS: In 24 patients with spinal vascular diseases, those who demonstrated progressive myelopathy with T2 hyperintensity in the spinal cord on magnetic resonance imaging (MRI) were diagnosed as patients with congestive myelopathy. We further examined the clinical courses, MRI findings, and reversibility of these cases. RESULTS: Venous congestion was judged to be a cause of neurological deterioration in 13 patients (7 DAVFs, 6 intradural AVMs). The T2 signals on these patients' MRI scans were located in the center and extended over several levels not corresponding to distribution of ischemia due to arterial steal. Of the patients who were diagnosed with congestive myelopathy, no differences between those with DAVFs and those with intradural AVMs were apparent in terms of clinical manifestations and reversibility. Eight (four DAVFs, four intradural AVMs) of 13 patients experienced neurological improvement after treatment. All patients with poor outcomes had intervals from onset of more than 3 years and showed contrast enhancement of the spinal cord on MRI studies. CONCLUSION: Spinal intradural AVMs as well as spinal DAVFs can be a cause of venous congestive myelopathy. Regardless of its etiology, congestive myelopathy is potentially reversible if properly diagnosed and treated.

Adult↗
PubMed2001

Carcinoma of the uterine cervix: twice- versus once-weekly high-dose-rate brachytherapy.

PURPOSE: To compare the effectiveness and safety of once- versus twice-weekly high-dose-rate (HDR) brachytherapy for cervical cancer. MATERIALS AND METHODS: From 1980 to 1997, 124 consecutive previously untreated patients with cervical cancer were treated with external-beam irradiation (50 Gy) and HDR brachytherapy. Clinical stages were I, 4 (3%) patients; II, 51 (41%); III, 64 (52%); and IV, 5 (4%). From 1980 to 1992, 74 patients (group A) were treated with HDR brachytherapy once weekly (about three fractions of 7 Gy each to point A [2 cm superior and 2 cm lateral to the inferior end of the intrauterine radioactive source]), while from 1992 to 1997, 50 patients (group B) were treated twice weekly (about six fractions of 4.5 Gy each to point A). RESULTS: Overall survival rate at 5 years was 65.2% in group A and 65.3% in group B (P=.96). Local recurrence-free survival rate at 5 years was 69% (51 of 74 patients) in group A and 90% (45 of 50 patients) in group B (P<.001). The rate of grade 2 (moderate) and grade 3 (severe) complications was significantly lower in group B (6% vs. 32% in group A, P<.001). At multivariate analysis, the variables significantly associated with increased local-regional recurrence rates were having stage III-IV lesions (P=.04) and with fewer than six sessions of HDR brachytherapy (P=.02). CONCLUSION: The twice-weekly HDR regimen may improve the local control rate with fewer complications.

Adenocarcinoma↗
PubMed2001

Prolonged mild hypothermia therapy protects the brain against permanent focal ischemia.

BACKGROUND AND PURPOSE: The efficacy of hypothermic intervention for permanent focal ischemia has yet to be clarified. This study investigated the effect of a prolonged moderate or mild hypothermia on permanent focal ischemia in rats. METHODS: Two permanent focal ischemia models in male Sprague-Dawley rats were used. Moderate (30 degrees C, in experiment 1) or mild (33 degrees C, in experiment 2) hypothermia was achieved at the time of the induction of focal ischemia and was maintained for 2 hours under general anesthesia. Thereafter, the hypothermic condition was maintained by means of a cold room for a total of 24 hours. The infarct volume and neurological function were analyzed for a maximum of 21 days and compared with that of the normothermia group. Regional cerebral blood flow was monitored for 6 hours in the ischemic core and penumbra region. RESULTS: In experiment 1, the total infarct volume in the normothermic group was 368+/-59 mm(3); in contrast, it was significantly smaller in the hypothermia group: 169+/-33 mm(3) at 48 hours (mean+/-SEM, P:<0.05). In experiment 2, the infarct volume was 211+/-19 mm(3) in the normothermia group and 88+/-15 mm(3) in the hypothermia group at 21 days (P:<0.05). There were significant differences in neurological function from days 2 through 21 between the two groups. Mean regional cerebral blood flow in the penumbra region increased to a level >50% of baseline. CONCLUSIONS: Prolonged mild hypothermia suppressed the development of cerebral infarct and neurological deficit chronically after the induction of permanent focal ischemia.

Animals↗
PubMed2001

Broad-spectrum and selective serine protease inhibitors prevent expression of platelet-derived growth factor-BB and cerebral vasospasm after subarachnoid hemorrhage: vasospasm caused by cisternal injection of recombinant platelet-derived growth factor-BB.

BACKGROUND AND PURPOSE: Plasma serine protease cascade, including the complement system and thrombin, is activated in the subarachnoid space during the acute phase after subarachnoid hemorrhage (SAH). To examine the effect of protease cascade-based inflammation and subsequent vascular repair in the development of cerebral vasospasm, we examined the effect of 2 synthetic serine protease inhibitors-FUT-175, an inhibitor of thrombin and the complement system, and argatroban, a selective inhibitor of thrombin-on the development of cerebral vasospasm in a rabbit SAH model. METHODS: One hundred Japanese White male rabbits were used in the study. The SAH was simulated by a single injection of autologous arterial blood into the cisterna magna. To evaluate the development of cerebral vasospasm, the caliber of the basilar artery was measured on x-ray film before and at 2 days after SAH. Nine groups of rabbits (n=6 each) were treated with continuous intravenous injection of FUT-175 (2.5, 5, 10, or 20 mg/d), argatroban (1.25, 2.5, or 5 mg/d), or the same amount of saline (vehicle) for 48 hours, starting 40 minutes after SAH. Two days after SAH, the expression of homodimer of platelet-derived growth factor-BB (PDGF-BB) in the basilar artery was examined with immunohistochemical techniques. In 20 normal rabbits, 5 microg of recombinant PDGF-BB or vehicle was injected into the cisterna magna, and the basilar arteries were examined on angiograms for 48 hours. RESULTS: Significant differences were observed in the caliber of the basilar arteries between the vehicle group and the groups with the 3 larger doses of FUT-175 (vehicle, 52+/-5.0%; 5 mg, 79+/-5.7%; 10 mg, 80+/-2.5%; 20 mg, 80+/-3.7%) and between the vehicle group and the groups with the 2 larger doses of argatroban (vehicle, 52+/-6.4%; 2.5 mg, 81+/-9.0%; 5 mg, 85+/-4.1%) (P<0.05). In the histological examination, administration of effective doses of FUT-175 or argatroban suppressed the expression of PDGF-BB in the endothelial and medial smooth muscle cell layers. Exogenous PDGF-BB caused delayed and prolonged vasoconstriction on normal basilar arteries. CONCLUSIONS: Activation of the serine protease cascade and/or thrombin after SAH was demonstrated to play an essential role in the development of cerebral vasospasm. The expression of PDGF-BB-like protein in the arterial walls correlated with the development of cerebral vasospasm. Elevated PDGF-BB level in the subarachnoid space was found to induce delayed and chronic vasoconstriction.

Animals↗
PubMed2001

Ebselen reduces cytochrome c release from mitochondria and subsequent DNA fragmentation after transient focal cerebral ischemia in mice.

BACKGROUND AND PURPOSE: The seleno-organic compound ebselen has both antioxidant and anti-inflammatory properties. Although ebselen has been shown to protect the brain against stroke, it is unclear how ebselen provides neuroprotection. In the present study the authors examined whether ebselen inhibits neuronal apoptosis resulting from transient focal cerebral ischemia in mice. The cytochrome c release and DNA fragmentation, both of which are biochemical markers of apoptosis, were compared between vehicle- and ebselen-treated mice. METHODS: Cerebral ischemia was induced by transient middle cerebral artery occlusion for 30 minutes in ICR mice under halothane anesthesia. Ebselen (10 mg/kg) was given orally twice, 30 minutes before ischemia and 12 hours after reperfusion. By Western blot analysis, we examined release of mitochondrial cytochrome c. To evaluate brain damage, the brain sections were treated for terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) and Nissl staining. Prolonged neuroprotective efficacy of ebselen was determined by counting neuronal nuclei (NeuN) immunopositive cells at 21 days after ischemia. RESULTS: - Cytochrome c release was detected in the ischemic hemisphere at 3 to 24 hours after ischemia. Ebselen treatment diminished the cytochrome c release at 12 and 24 hours. In addition, ebselen decreased both DNA fragmentation determined by TUNEL and brain damage volume at 3 days after ischemia. Furthermore, ebselen increased the number of NeuN immunopositive cells at 21 days after ischemia. CONCLUSIONS: These results indicate that ebselen attenuates ischemic neuronal apoptosis by inhibiting cytochrome c release. Ebselen may be a potential compound in stroke therapy.

Animals↗
PubMed2001

Expression of SR-PSOX, a novel cell-surface scavenger receptor for phosphatidylserine and oxidized LDL in human atherosclerotic lesions.

Receptor-mediated endocytosis of oxidized low density lipoprotein (Ox-LDL) by macrophages and the subsequent foam cell transformation in the arterial intima are key events in early atherogenesis. Recently, we have identified a novel macrophage cell-surface receptor for Ox-LDL by expression cloning from a cDNA library of phorbol 12-myristate 13-acetate-stimulated THP-1 cells, designated as the scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX). Here, we examined SR-PSOX expression in human atherosclerotic lesions. Total cellular RNA and fresh frozen sections were prepared from human carotid endarterectomy specimens (from 21 patients) and directional coronary atherectomy specimens (from 11 patients). Fragments of human aortas of 2 patients without visible atherosclerotic lesions served as negative controls. Quantitative reverse transcription-polymerase chain reaction demonstrated that SR-PSOX mRNA expression was prominent in atherosclerotic lesions but undetectable in normal aortas. Immunohistochemistry showed that SR-PSOX was predominantly expressed by lipid-laden macrophages in the intima of atherosclerotic plaques in carotid endarterectomy and directional coronary atherectomy specimens, although its expression was not detectable in normal arterial wall. Double-labeled immunohistochemistry confirmed that SR-PSOX is expressed by intimal macrophages. Taken together, SR-PSOX may be involved in Ox-LDL uptake and subsequent foam cell transformation in macrophages in vivo and thus may play important roles in human atherosclerotic lesion formation.

Animals↗
PubMed2001

Cerebral ischemic complications following intracranial bleeding in patients with moyamoya disease--three case reports.

Three patients with bleeding-type moyamoya disease suffered ischemic complications following their first episode of intracranial bleeding. The patients presented with intraventricular hemorrhage and suffered cerebral infarction on the 14th, 16th, and 11th days after the ictus, respectively. The clinical records revealed no obvious hypotension before progression to infarction and suggested that dehydration accelerated by the administration of hyperosmotic drugs was a contributing factor to the infarction. Two patients underwent superficial temporal artery-middle cerebral artery anastomoses in the chronic stages and have never experienced further ischemic complications. The other patient died despite receiving intensive care. Hemodynamic reserve may be severely impaired in patients with bleeding-type moyamoya disease. Adequate control of hydration is important to prevent cerebral infarction after intracranial bleeding in patients with moyamoya disease.

Adolescent↗
PubMed2001

[Bilateral carotid stenting for radiation-induced arterial stenosis].

We report a case of bilateral radiation-induced internal carotid artery (ICA) stenosis treated with stenting. A 67-year-old man experienced transient left hemiparesis several times, and it was diagnosed as a bilateral ICA stenosis by magnetic resonance angiogram (MRA) and cervical ultrasound sonogram (US). Ten years before, the patient had received radiation therapy (66 Gy) and radical resection for a squamous cell carcinoma (SCC) in the right infrapharyngeal space. A cerebral angiogram showed bilateral severe ICA stenosis (right; 90%, left; 99%). We diagnosed this as radiation-induced ICA stenosis, and performed carotid angioplasty with a self-expanding stent. The post-operative course was uneventful and the patient was discharged without neurological deficits. Carotid endarterectomy (CEA) is difficult in the case of carotid artery stenosis due to radiation-induced arterial injury. Carotid stenting may be an alternative treatment for such a patient.

Aged↗
PubMed2001

[Stenting for proximal subclavian and brachiocephalic artery occlusion--preliminary results].

The authors report the initial results, between January 1998 and February 2001, of stenting utilizing the brachial approach in seven patients for total occlusions at the following locations: two right subclavian, one brachiocephalic, and five left subclavian arteries. All lesions were associated with subclavian steal syndrome. Indications for the treatment included ischemic symptoms in the affected arm (seven patients), and vertebrobasilar insufficiency (five patients). A total of eight stents were implanted in six occluded arteries, resulting in a 75% procedural success rate. Procedural complications encountered were two subintimal dissections by a 0.035-inch guide wire during recanalization, and one stent dislodgement with migration. There was no stroke, presumably because of the previously reported preventive effect of delayed reversal of a stealing vertebral artery. Follow-up over a mean duration of 11 months revealed no sign or symptom of recurrence in cases with initial technical success. The results of the current study, with a literature survey, indicated that percutaneous transluminal angioplasty with primary stent deployment in an occluded prevertebral segment of the subclavian or the brachiocephalic artery should be considered as an available choice for treatment. Further points, such as some remaining technical and clinical problems, will require more experience and consideration.

Adult↗
PubMed2001

Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.

We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian cancer in Japan appear to be similar to those in Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common founder mutations unique to the Japanese population.

Adolescent↗
PubMed2001

[Problems involved in endovascular embolization of intracranial aneurysms with three-dimensional Guglielmi detachable coils].

We experienced nine cases of intracranial aneurysms which were treated with three-dimensional Guglielmi detachable coils (3D-GDC). 3D-GDC is useful in the construction of the initial frame for the embolization of aneurysms, but it also has certain disadvantages for achieving successful treatment. Nine patients with nine intracranial aneurysms were treated with 3D-GDC for initial framing from October, 1999 to September, 2000 at the National Cardio-Vascular Center, Japan. Angiographically complete and successful occlusion was performed in only three patients. Four patients developed parent artery stenosis due to small loops of the 3D-GDC protruding from the aneurysm. Two patients experienced incomplete occlusion because small loops of the 3D-GDC caused cells to form in the framing, and additional coils could not be inserted into some cells. 3D-GDC is useful as an initial framing coil, but we should be careful when placing additional coils into an aneurysm because we cannot predict the effect of the small loops of 3D-GDC on the embolization of aneurysms.

Aged↗
PubMed2001

[Stenting for the occlusive carotid and subclavian arteries in Takayasu arteritis].

The authors report the initial results of stenting in four patients of Takayasu arteritis for 11 occlusive carotid and subclavian arteries between January 1999 and December 2000. The lesions included stenoses of two right subclavian, three right common carotid, two left common carotid, and two left subclavian arteries, and total occlusion of two subclavian arteries. A total of 14 stents were implanted in 10 arterial lesions, resulting in a 91% procedural success rate. One failure was due to inability to cross the total occlusion of the subclavian artery. Procedural complications and problems were pain during balloon angioplasty in three patients, vaso-vagal reflex in two, carotid artery perforation associated with transient horseness in one, and stent migration in one. There was no permanent morbidity. Follow-up over a mean duration of 12 months revealed one symptomatic recurrence of left subclavian stenosis, followed by a successful re-dilatation. The results of the current study indicated that primary stenting is an excellent therapeutic option for the occlusive carotid and subclavian arteries in Takayasu arteritis. A long-term follow-up is required to determine the response or behavior of stented segments of the affected arteries.

Adult↗
PubMed2000

Prospective reevaluation of risk factors in mother-to-child transmission of hepatitis C virus: high virus load, vaginal delivery, and negative anti-NS4 antibody.

Of 21,791 pregnant women screened in Tottori Prefecture, Japan, 127 (0.58%) were positive for anti-hepatitis C virus (HCV) antibody and 84 (0.39%) were positive for HCV RNA. Of 84 children followed up for at least 6 months, 7 (8%) were infected. All of them were born to 26 mothers with a high virus load (HVL; >/=2.5x106 RNA copies/mL [27%]), compared with 0 of 58 children born to non-HVL mothers (P<.001). Because all the infected children were vaginally delivered, the infection rate among 16 vaginally delivered children born to the HVL mothers was as high as 44%. The prevalence of anti-NS4 antibody in the mothers with an infectious HVL was significantly lower than that in the mothers with a noninfectious HVL (P=.048). Analysis of our results suggests that maternal HVL, vaginal delivery, and negative anti-NS4 antibody are significant risk factors for the mother-to-child transmission of HCV.

Delivery, Obstetric↗
PubMed2000

Infarct tolerance accompanied enhanced BDNF-like immunoreactivity in neuronal nuclei.

A prolonged period (48 h) of cortical spreading depression (CSD) induced resistance against severe focal cerebral ischemia (infarct tolerance), however, the mechanism behind this is unknown. The infarct tolerance was a transient phenomenon; the resistance increased linearly for the initial 12 days, peaking from 12 to 15 days after a preconditioning of CSD, and was decreased thereafter. This study examined the time course of brain-derived neurotrophic factor (BDNF), heat shock protein (hsp)27 and 70, and glial fibrillary acidic protein (GFAP) expressions after CSD in the brain. Immunohistochemical expression of BDNF, hsp27, hsp70, or GFAP following a prolonged period of CSD induced by KCl-infusion, or following NaCl-infusion was analyzed by regional densitometry for 24 days in the rat neocortex. In addition, BDNF protein was measured quantitatively by two-site ELISA assay in the neocortex (n=6 at each time point). The GFAP expression was elevated in astrocytes (compared to the normal level of immunodensity) during the period peaking on day 3-6 following the CSD. The hsp27 immunoreactivity was also elevated in astrocytes from day 1 to 12 peaking on day 1 and 6, but there was no expression of hsp70 during the period following CSD. The immunoreactivity for BDNF was elevated in neurons from day 0 to 18 peaking on day 1 and 6. The protein levels of BDNF in the neocortex were significantly elevated from day 0 to 12 peaking on days 0 and 6 (compared to the normal level) (P<0.05). Using a laser-scanning confocal imaging system, the BDNF-like immunoreactivity in neuronal nuclei was found to increase linearly peaking on day 12, which correlated well with the development of infarct tolerance. The intranuclear increase in BDNF-like protein might contribute to the induction of infarct tolerance in the brain.

Animals↗
PubMed2000

Neuroprotection by MAPK/ERK kinase inhibition with U0126 against oxidative stress in a mouse neuronal cell line and rat primary cultured cortical neurons.

Oxidative stress is implicated in the pathogenesis of neuronal degenerative diseases. Oxidative stress has been shown to activate extracellular signal-regulated kinases (ERK)1/2. We investigated the role of these mitogen-activated protein kinases (MAPKs) in oxidative neuronal injury by using a mouse hippocampal cell line (HT22) and rat primary cortical cultures. Here, we show that a novel MAPK/ERK kinase (MEK) specific inhibitor U0126 profoundly protected HT22 cells against oxidative stress induced by glutamate, which was accompanied by an inhibition of phosphorylation of ERK1/2. U0126 also protected rat primary cultured cortical neurons against glutamate or hypoxia. However, U0126 was not protective against death caused by tumor necrosis factor alpha (TNFalpha), A23187, or staurosporine. These results indicate that MEK plays a central role in the neuronal death caused by oxidative stress.

Animals↗