樋口 佳則

We evaluated the results of stereotactic radiosurgery (SRS) alone using gamma knife (GK) for selected patients with 1-10 brain metastases without prophylactic whole-brain radiation therapy (WBRT) among JLGK0901-eligible cases. Seven hundred seventy-eight consecutive cases meeting the following JLGK0901 study inclusion criteria were analyzed: (1) newly diagnosed brain metastases, (2) 1-10 brain lesions, (3) less than 10 cm 3 volume of the largest tumor, (4) less than 15 cm 3 total tumor volume, (5) no magnetic resonance (MR) findings of cerebrospinal fluid (CSF) dissemination, and (6) no impaired activity of daily living [<70 Karnofsky Performance Score (KPS)] due to extracranial disease. At initial treatment, all lesions were irradiated with SRS without upfront WBRT. Thereafter, enhanced magnetic resonance imaging (MRI) was applied every 2-3 months, and new distant lesions were appropriately retreated with SRS or WBRT. We divided patients according to tumor number: single lesion for group A (280 cases), 2 for group B (135), 3-4 for group C (148), 5-6 for group D (93), and 7-10 for group E (122). Differences among groups were compared in terms of overall, neurological, qualitative, and new-lesion-free survival (NLFS). Median age was 65 years (range 26-92 years). There were 505 men and 273 women. The primary organ was lung in 579 patients, gastrointestinal tract in 79, breast in 48, urinary tract in 34, and others/unknown in 38. Mean survival time was 0.72 years (0.83 years for 1, 0.69 years for 2, 0.69 years for 3-4, 0.59 years for 5-6, and 0.62 years for 7-10 metastases). On multivariate analysis, significant poor prognostic factors for overall survival (OS) were active systemic disease, poor (<70) initial KPS, and male gender. Neurological survival and qualitative survival at 1 year were 92.7% and 88.2%, respectively. NLFS at 6 months and 1 year were 69.8% and 43.8%, respectively. There were statistically significant differences in new lesion emergence between groups A and B and between groups B and C. SRS using GK provides excellent results in selected patients with 1-10 brain lesions, without prophylactic WBRT. This study revealed that brain lesion number has no effect on any of the four types of survivals, which is anticipated to be confirmed by the JLGK0901 study.

Purpose: We examined the effects of manganese (III) meso-tetrakis (dicthyl-2-5-imidazole) porphyrin, a metalloporphyrin antioxidant (MPA), on neural tissue radiation toxicity in vivo and on tumour cell radiosensitivity in vitro. Materials and methods: MPA was administered directly into the right lateral ventricle of young adult, male Sprague-Dawley rats (0 or 3.4 mu g) 3 h before treatment with a single fraction, 100 Gy radiation dose delivered to the left brain hemisphere. The effects of treatment on radiation responses were assessed at different time points following irradiation. Results: MPA treatment prior to brain irradiation protected against acute radiation-induced apoptosis and ameliorated delayed damage to the blood-brain barrier and radiation necrosis, but without producing a discernible increase in tissue superoxide disumtase (SOD) activity. In vitro, MPA pretreatment protected against radiation-induced apoptosis in primary neuronal cultures and increased clonogenic survival of irradiated rat glioma C6 cells, but had no discernible effect on radiation-induced DNA double-strand breaks. MPA, a low molecular weight SOD mimic, significantly increased mitochondrial SOD activity in C6 cells, but not total cellular SOD activity. MPA up-regulated C6 expression of heme-oxygenase I (HO-1), an endogenous radioprotectant, but had no effect on HO-I levels in human astrocytoma U-251 cells, human prostatic carcinoma LNCaP cells, or primary rat brain microvascular endothelial cells in vitro, nor on brain tissue HO-I expression levels in vivo. Conclusions: Metalloporphyrin antioxidants merit further exploration as adjunctive radioprotectants for cranial radiotherapy/radiosurgery applications, although the potential for tumour protection must be carefully considered.

Objective: We evaluated the effectiveness of stereotactic radiosurgery alone for patients with 1-4 brain metastases without prophylactic whole-brain radiation therapy (WBRT). Materials and Methods: 762 consecutive cases with no more than 4 brain metastases treated under the same local treatment protocol were analyzed. Large tumors (>3 cm in mean diameter) were totally removed or irradiated with hypofractionated stereotatcic radiotherapy using the Gamma Knife (R) (GK), while smaller lesions (<= 3 cm) were all irradiated with GK radiosurgery. No upfront WBRT was applied and new distant lesions were appropriately retreated with GK radiosurgery. Tumor progression-free, overall, neurological, qualitative and new lesion-free survival curves were calculated by the Kaplan-Meier method. Results: In total, I,277 separate GK procedures were required to treat 3,878 lesions. The tumor control rates at I year were 98.0% in tiny (<1 cm in mean diameter), 89.5% in small (<= 1 but <2 cm), 80.1% in medium-sized (<= 2 but <3 cm), and 61.6% in large (>= 3 cm) lesions. The median survival period was 0.77 years. Neurological, qualitative and new lesion-free survival rates at 1 year were 92.0, 85.9 and 63.6%, respectively. New lesions and salvage treatments were more frequent in patients with multiple brain metastases than in those with a single metastasis (p < 0.0001). The number of salvage GK procedures for new distant lesions was zero in 375 (67.0%), one in 91(16.3%), two in 54 (9.6%), and >= 3 in 40 cases (7.1%). Conclusion: In meeting the goal of preventing neurological death and maintaining activities of daily living for patients with 1-4 brain metastases from various cancers, GK alone provides excellent palliation without prophylactic WBRT. New distant lesions were quite well controlled with salvage GK treatment alone. Copyright (C) 2010 S. Karger AG, Basel

To evaluate the effects of bromocriptine on bladder function in Parkinson's disease (PD) patients and compare these effects with those of (L-dopa). We recruited 8 patients with PD. Urodynamic study (UDS) was performed before and I hour after administering 100 mg L-dopa/decarboxylase inhibitor (DCI) and 2.5 hours after administering 7.5 mg bromocriptine. After the bromocriptine administration, urinary urgency aggravated. UDS revealed a decreased bladder volume at which detrusor overactivity (DO) was initiated, a decreased bladder volume at first sensation of bladder filling (FSV) (P < 0.05), an increased maximum Watts Factor value (WFmax) (detrusor contractility), a decreased Abrams-Griffiths (AG) number (urethral obstruction), and a decreased postvoid residual (PVR) (P < 0.01). Similarly, after the L-dopa administration, urinary urgency aggravated. UDS revealed an aggravated DO (P < 0.05), a decreased FSV and bladder capacity (P < 0.01, 0.05), an increased WFmax (P < 0.05), an increased AG number, and a decreased PVR (P < 0.01). A single dose of bromocriptine proved to exacerbate urinary urgency and DO in the storage phase, and improve bladder emptying through increased detrusor contractility and decreased bladder outlet obstruction, within hours. With the exception of bladder outlet obstruction, these effects of bromocriptine are similar to the effects of L-dopa, albeit slightly less pronounced. (C) 2009 Movement Disorder Society

Purpose: To evaluate the efficacy and toxicity of staged stereotactic radiotherapy with a 2-week interfraction interval for unresectable brain metastases more than 10 cm(3) in volume. Patients and Methods: Subjects included 43 patients (24 men and 19 women), ranging in age from 41 to 84 years, who had large brain metastases (&gt; 10 cc in volume). Primary tumors were in the colon in 14 patients, lung in 12, breast in 11, and other in 6. The peripheral dose was 10 Gy in three fractions. The interval between fractions was 2 weeks. The mean tumor volume before treatment was 17.6 +/- 6.3 cm(3) (mean +/- SD). Mean follow-up interval was 7.8 months. The local tumor control rate, as well as overall, neurological, and qualitative survivals, were calculated using the Kaplan-Meier method. Results: At the time of the second and third fractions, mean tumor volumes were 14.3 +/- 6.5 (18.8% reduction) and 10.6 +/- 6.1 cm(3) (39.8% reduction), respectively, showing significant reductions. The median overall survival period was 8.8 months. Neurological and qualitative survivals at 12 months were 81.8% and 76.2%, respectively. Local tumor control rates were 89.8% and 75.9% at 6 and 12 months, respectively. Tumor recurrence-free and symptomatic edema-free rates at 12 months were 80.7% and 84.4%, respectively. Conclusions: The 2-week interval allowed significant reduction of the treatment volume. Our results suggest staged stereotactic radiotherapy using our protocol to be a possible alternative for treating large brain metastases. (C) 2009 Elsevier Inc.

Object. The authors compared results of Gamma Knife surgery (GKS) for brain metastases obtained at 2 institutions in Japan. Methods. They analyzed a consecutive series of 2390 patients with brain metastases who underwent GKS from 1998 through 2005 in 2 institutes (1181 patients in Chiba: 1209 in Mito). In the 2 facilities, I neurosurgeon each was responsible for diagnosis, patient selection. GKS procedures. and follow-up (T.S. in Chiba, M.Y. in Mito). Even if tumor numbers exceeded 4, all visible lesions were irradiated with a total skull integral dose (TSID) of &lt;= 10-12 J. No prophylactic whole-brain radiotherapy (WBRT) was applied. If new distant lesions were detected, salvage GKS was appropriately performed. Results. The distributions of patient and treatment factors did not differ between institutes. The most common primary tumors were lung cancer (1572 patients), followed by gastrointestinal tract (316). breast (211), kidney (113), and other cancers (159). The median survival periods were 7.7 months in Chiba and 7.0 months in Mito (p = 0.0635). The significant poor prognostic factors for overall survival were active extracranial disease status, male sex, and low initial Karnofsky Performance Scale score on multivariate analysis (all p &lt; 0.0001). The neurological survival rates at 1 year were 86.6% in Chiba and 84.2% in Mito (p = 0.3310). Conclusions. This 2-institute study demonstrated no significant institutional differences in any of the treatment result items. Gamma Knife surgery for brain metastases without prophylactic WBRT prevents neurological death and allows a Patient to maintain good brain condition. However, there is I important patient selection criterion: regardless of how many tumors there are, all lesions can be irradiated with a TSID of &lt;= 12 J. (DOI: 10.3171/JNS/2008/109/12/S18)

Object. The authors prospectively analyzed volume changes in vestibular schwannomas (VSs) after stereotactic radiosurgery. Methods. One hundred Consecutive patients with unilateral VS treated with Gamma Knife Surgery (GKS) at Chiba Cardiovascular Center between 1998 and 2006 were analyzed in this study. For each lesion the Gd-enhanced volume was measured serially every 3 months in the 1st year, then every 6 months thereafter, using volumetric software. The frequency and degree of transient tumor expansion were documented and possible prognostic factors were analyzed. Concurrently, neurological deterioration involving trigeminal, facial, and cochlear nerve functions were also assessed. Results. The mean observation period was 65 months (range 25-100 months). There were 32 men and 68 women whose mean age was 59.1 years (range 29-80 years). Tumor volumes at GKS averaged 2.7 cm(3) (range 0.1-13.2 C 113), and the lesions were irradiated at the mean 52.2% isodose line for the tumor margin (range 50-67%), with a mean dose of 12.2 Gy (range 10.5-13 Gy) at the periphery. The tumor Volume was increased by 23% at 3 months and 27% at 6 months. Tumors shrank to their initial size over a mean period of 12 months. The maximum volume increase was &lt; 10% (no significant increase) in 26 patients, 10-30% in 23, 30-50% in 22, 50-100% in 16, and &gt; 100% in 13. The peak tumor expansion averaged 47% (range 0-613%). A high-dose (&gt;= 3.5 Gy/min) treatment appears to be the greatest risk factor for transient tumor expansion, although the difference did not reach statistical significance. Transient facial palsy and facial dysesthesia correlated strongly with tumor expansion, but only half of the hearing loss was coincident with this phenomenon. Conclusions. Transient expansion of VSs after GKS was found to be much more frequent than previously reported, strongly Suggesting a correlation with deterioration of facial and trigeminal nerve functions.

Objective: There are two hypotheses for the pathogenesis of hemifacial spasm (HFS): abnormal cross-transmission between the facial nerve fibers at a site of vascular compression, and hyperactivity of the facial nucleus. To further elucidate the mechanism of HFS, we established an animal model. We applied chronic electrical stimulation (CES) to the facial nucleus in rats, and clarified functional and morphological changes in the nucleus. Method: Under anesthesia, a novel intracranial electrode was stereotactically implanted in the facial nucleus of six rats. CES of the facial nucleus via the implanted electrode was applied for 5 min daily for three weeks (CES animals). Facial electromyograms (EMGs) were recorded at rest and during electrical stimulation to study the excitability of the facial nucleus at 1, 2, and 4 weeks after initiating CES. As control animals, six rats were implanted with intracranial electrodes, but did not undergo CES. Electrophysiological studies of the control animals were performed using the same protocol as in the CES animals. Result: Spontaneous abnormal movement of the facial muscle mimicking HFS did not occur. Four weeks after starting CES, one of the six CES animals developed an abnormal EMG response with a latency of 10 ms. No control animals developed such a response. Conclusions: CES of the facial nucleus can produce an abnormal EMG response very similar to the abnormal muscle response (AMR) characteristic of HFS patients. Kindling-like hyperactivity of the facial nucleus induced by CES is the cause of the AMR, suggesting a pathogenesis of HFS. (C) 2006 Elsevier Ltd. All rights reserved.

Objective: The effectiveness of gamma knife surgery (GKS) for brain metastases without prophylactic whole brain radiation therapy (WBRT) was analyzed and indications for and limitations of the local treatment protocol are discussed herein. Methods: Among 1,474 cases with newly diagnosed brain metastases, 1,386 patients who satisfied the following 3 criteria were analyzed in this study, 1) newly diagnosed brain metastases, 2) tumor number and size within 10 Joules of total skull internal dose, 3) no symptomatic carcinomatous meningitis. Large tumors were totally removed or irradiated by hypo-fractionated stereotactic radiotherapy using the gamma knife, while all small lesions were irradiated with GKS. Without upfront WBRT, new distant lesions identified on follow-up MRI every 2 to 3 months were appropriately re-treated with GKS. Overall, neurological, qualitative and new lesion-free survival curves were calculated and compared according to tumor number. Results: In total, 2,355 separate GKS sessions were required to treat 13,319 lesions. The median overall survival period was 9.4 months. Neurological, qualitative, and new lesion-free survival rates at one year were 88.5%, 81.5% and 56.3%, respectively. The higher the tumor number, the poorer the prognosis for each type of survival. Conclusion: In meeting the goal of preventing neurological death and maintaining activities of daily living for patients with brain metastases who satisfy the 3 aforementioned inclusion criteria, GKS alone provides excellent palliation without prophylactic WBRT. Close observation and appropriate salvage treatment are essential.

Object. The authors analyzed the effectiveness of Gamma Knife surgery (GKS) for metastatic brain tumors without adjuvant prophylactic whole-brain radiotherapy (WBRT). Salvage GKS was performed as the sole treatment for new distant lesions. Methods. Among 1127 patients in whom new brain metastases had been diagnosed, 97 who met one or more of the following three criteria were excluded from the study: any surgically inaccessible huge (&gt;= 35 mm) lesion; tumor number and size requiring an internal skull dose exceeding 10 J; or symptomatic carcinomatous meningitis. Thus, 1030 consecutive patients formed the basis for this study. Huge tumors were totally removed, whereas smaller lesions were treated with GKS. No adjuvant WBRT was given prior to GKS, and new distant lesions were appropriately retreated with GKS. Overall, neurological and new lesion-free survival curves were calculated and the prognostic values of covariates were obtained. In total, 1853 separate GKS sessions were required to treat 10,163 lesions. The patients' median overall survival period was 8.6 months. Neurological survival and new lesion-free rates at I year were 89.1 and 49.3%, respectively. In a multivariate analysis, the significant factors for poor prognosis were the development of more than four new brain metastases and active extracranial disease. Conclusions. In meeting the goal of preventing neurological death and maintaining activities of daily living for patients with brain metastases, GKS alone provides excellent palliation without prophylactic WBRT. New distant lesions were quite well controlled with GKS salvage treatment alone.

Objective: We retrospectively analyzed the effectiveness of Gamma Knife surgery (GKS) for metastatic brain tumors from lung cancer without prophylactic whole brain radiation therapy. Methods: Six hundred eight consecutive patients who satisfied the following 5 criteria were analyzed: (1) lung cancer primary; (2) no surgically inaccessible lesions; (3) tumor number and size limited to 10 J of total skull internal dose; (4) no symptomatic carcinomatous meningitis; (5) Karnofsky performance status score no lower than 70 due to systemic disease. Large tumors were totally removed, while smaller lesions were all irradiated with GKS. New lesions detected with follow-up magnetic resonance imaging were appropriately re-treated with GKS. Overall survival (OS), neurological survival (NS), qualitative survival (QS) and new lesion-free survival curves were calculated and the prognostic values of covariates were obtained. Results: In total, 1,101 separate sessions were required to treat 6,427 lesions. This series includes 68 small cell cancers and 80 craniotomies. The median OS period was 10.4 months. In multi-variate analysis, significant prognostic factors for OS were extracranial disease (risk factor: active), Karnofsky performance status score (&lt; 70) and gender (male). NS and QS at I year were 88.0 and 81.3%, respectively. The only significant poor prognostic factor for NS was carcinomatous meningitis. Male gender, active extracranial disease, low Karnofsky performance status score, magnetic resonance imaging evidence of carcinomatous meningitis and a large total tumor volume were significant factors influencing QS. New lesion-free survival at 6 months was 71.5%. The treatment cost of this protocol was estimated USD 9,000 per patient, which is nearly the same as that of GKS with upfront whole brain radiation therapy. Conclusion: In terms of NS and QS, GKS alone for metastatic brain tumors from lung cancer provides excellent palliation without prophylactic whole brain radiation therapy. Close observation and appropriate salvage treatment are essential for prevention of neurological death and maintaining of activities of daily living. Copyright (c) 2006 S. Karger AG, Basel.

Objective. The purpose of this retrospective study was to evaluate results of a local treatment protocol using gamma knife surgery (GKS) for brain metastases without upfront whole brain radiation therapy (WBRT). Methods. Results for 521 consecutive patients satisfying the following 3 criteria were analysed: 1) a maximum of 3 tumours with a diameter of 25mm or more; 2) no prior WBRT; 3) no surgically inaccessible large (&gt; 30mm) tumours. Large tumours were surgically removed and all smaller lesions were treated by GKS without upfront WBRT. New lesions, detected with follow-up MRI, were appropriately treated with repeat GKS. Overall survival ( OS), neurological survival (NS), qualitative survival (QS) and new lesion-free survival (NLFS) curves were calculated and the prognostic values of covariates were obtained. OS and NS were compared according to tumour number. Results. In total, 1023 separate sessions were required to treat 4562 lesions. The primary organs were lung in 369 patients, gastrointestinal tract in 70, breast in 33, urinary tract in 24, and others/unknown in 25. The median OS period was 9.0 months. On multivariate analysis, the significant prognostic factors for OS were found to be extracranial disease ( risk factor: active), Karnofsky performance status (KPS) score (&lt; 70) and gender ( male). NS and QS at one year were 85.6% and 73.0%, respectively. The only significantly poor prognostic factor for NS was carcinomatous meningitis. NLFS at 6 months was 68.9%. For both OS and NS, the differences between a few (&lt;= 3) and many (4-10) brain lesions were not significant (OS: p = 0.3128, NS: p = 0.5509). Patients with numerous (&gt; 10) tumours had a significantly poorer prognosis than those with &lt;= 10. Conclusion. Our protocol, aggressively applying GKS, provides excellent results in selected patients with &lt;= 10 brain lesions and no carcinomatous meningitis.

Object. The authors assessed the diagnostic value of Tl-201 Cl single-photon emission computerized tomography (SPECT), performed after gamma knife surgery (GKS) for metastatic brain tumors in differentiating tumor recurrence from radiation injury. Methods. Of 6503 metastatic brain tumors treated with GKS, Tl-201 SPECT was required in 72 to differentiate between tumor recurrence and radiation injury. When the Tl index was greater than 5, the lesion was diagnosed as a tumor recurrence. When the index was &lt; 3.0 it was called radiation injury. In cases with a Tl index between 3 and 5, Tl-201 SPECT was repeated once per month until the Tl index was greater than 5 or less than 3. If the Tl index fluctuated between 3 and 5 for 2 months, the lesion was diagnosed as radiation injury. The final diagnosis was based on histological examination or clinical course. The sensitivity of the method was 91%; thus Tl-201 SPECT is effective for differentiating between tumor recurrence and radiation injury in metastatic brain tumors treated with GKS. Caution is necessary, however, for the following reasons: 1) simple interinstitutional comparisons of Tl indices are not possible because measurement methods are institute specific; 2) steroid administration decreases the Tl index to a variable degree; and 3) a severe radiation injury lesion, as is often seen after repeated GKS or very high dose GKS, may have a Tl index greater than 5. Conclusions. Used with critical insight Tl-201 Cl SPECT can be useful in distinguishing between tumor regrowth and radiation necrosis in patients with cerebral metastases.

The authors prospectively treated 18 consecutive patients with low-grade oligodendroglial tumors without postoperative radiotherapy. The treatment strategy was as follows: follow-up after total resection and chemotherapy after subtotal resection or biopsy. All patients were alive and 17 patients (94%) were progression-free after a median follow-up of 4.7 years. The results suggested that radiotherapy could be postponed until clinical progression in the treatment of low-grade oligodendroglial tumors.

We studied the bleeding risk during latency period after gamma knife surgery (GKS) for small (3 cm or less) cerebral arteriovenous malformations (AVMs). We analyzed 720 cases with a natural history and 100 cases with GKS. The incidence of bleeding was calculated from the data of the former cases according to the history of bleeding and their age and was compared with the actual number obtained from the latter. The estimated incidence of bleeding was 1.6 for unruptured AVMs and 5.5 for ruptured AVMs, whereas the actual incidence of bleeding was 2 for unruptured and 0 for ruptured. The difference was statistically significant in the ruptured but was not significant in the unruptured.<br> These results lead us to conclude that the bleeding risk during latency period after GKS for small AVMs is almost the same in the unruptured, but is decreased in the ruptured.<br>

OBJECTIVE: To investigate the potential operative morbidity in posteroventral pallidotomy (PVP) for patients with Parkinson's disease. METHODS: We designed a retrospective study that included 796 consecutive patients (mean age, 64.9 yr; male, 559; female, 237) with Parkinson's disease. All PVPs (simultaneous bilateral PVP, n = 272; sequential bilateral PVP, n = 88; unilateral PVP, n = 436) were performed during a 7-year period. The total number of operations was 884, and the number of PVP procedures was 1156. In 108 patients, ventral diate nucleus thalamotomy was performed simultaneously. RESULTS: The overall complication rate, including temporary problems, was 15.3% of 884 operations. Permanent complications occurred in 3.6% of total operations. Intracranial hemorrhage occurred in 24 operations (2.7%). In seven of them, the patients required craniotomy and hematoma evacuation and sustained a disabling motor deficit (0.8%). Intracranial hemorrhage occurred more often in patients who underwent microelectrode recording and had a history of chronic hypertension. Hemiparesis without intracranial hematoma occurred in 12 operations (1.4%). Microelectrode-recording was a risk factor for postoperative hemiparesis without hemorrhage.)n 19 operations (2.1%), patients developed a partial visual field deficit. Speech disturbance after surgery was observed in 23 operations (2.6%) but resolved in 17 by 1 week after 1 surgery. In 55 operations (6.2%), patients developed postoperative confusion. This occurred more often in elderly patients and those with advanced disease. In 17 operations (1.9%), patients required observation in the intensive care unit because of postoperative hypotension. CONCLUSION: Complications from stereotactic pallidotomy were not frequent. ever, the residual symptoms from complications can be serious in many cases.

Apolipoprotein E (apoE) is a lipid binding protein that plays an important role in tissue repair following brain injury. In the present studies, we have investigated whether apoE affects the behavioral toxicity of high charge, high energy (HZE) particle radiation. METHODS: Sixteen male apoE knockout (KO) mice and sixteen genetically matched wild-type (WT) C57BL mice were used in this experiment. Half of the KO and half of the WT animals were irradiated with 600 MeV/amu iron particles (2Gy whole body). The effect of irradiation on motor coordination and stamina (Rotarod test), exploratory behavior (open field test), and spatial working and reference memory (Morris water maze) was assessed. ROTAROD TEST: Performance was adversely affected by radiation exposure in both KO and WT groups at 30 d after irradiation. By 60 d after radiation, the radiation effect was lost in WT, but still apparent in irradiated KO mice. OPEN FIELD TEST: Radiation reduced open field exploratory activity 14, 28, 56, 84, and 168 d after irradiation of KO mice, but had no effect on WT mice. MORRIS WATER MAZE: Radiation adversely affected spatial working memory in the KO mice, but had no discernible effect in the WT mice as assessed 180 d after irradiation. In contrast, irradiated WT mice showed marked impairment of spatial reference memory in comparison to non-irradiated mice, while no effect of radiation was observed in KO mice. CONCLUSIONS: These studies show that apoE expression influences the behavioral toxicity of HZE particle radiation and suggest that apoE plays a role in the repair/recovery from radiation injury of the CNS. ApoE deficiency may exacerbate the previously reported effects of HZE particle radiation in accelerating the brain aging process.

Background and Purpose-Subarachnoid hemorrhage (SAH) increases production of vascular extracellular superoxide anion (O-2(-)) We examined whether overexpression of murine extracellular superoxide dismutase (EC SOD) alters SAH induced cerebral vasospasm oxidative stress and neurological outcome Methods-Mice exhibiting a 2 fold increase in vascular EC SOD and wild type (WT) littermates were subjected to sham surgery or SAH by perforation of the right anterior cerebral artery Neurological deficits were scored 72 hours later Middle cerebral artery (MCA) diameter was measured or immunohistochemically stained for nitrotyrosine Results-MCA diameter (mean+/-SD) was greater in EC SOD versus WT mice after SAH but not sham surgery (EC SOD SAH=56+/-10 mum WT SAH=38+/-13 mum [P&lt;0 01] EC SOD sham=99+/-16 &mu;m WT sham=100+/-15 &mu;m) SAH decreased median (range) neurological score (scoring scale 9 to 39 no deficit=39) versus shams but there was no difference between EC SOD and WT groups (EC SOD SAH=26 [23 to 30] WT SAH=23 [19 to 29] [P=0 27] EC SOD sham=39 [39] WT sham=39 [39]) Sensory motor deficits correlated with MCA diameter (P&lt;0 001) but worsened primarily between 60 and 50 mum plateauing below this threshold The percentage of mice with MCA nitrotyrosine staining increased after SAH in WT (sham=29% SAH=100% [P&lt;0 05]) but not EC SOD (sham=33% SAH=44% [P=0 80]) mice Conclusions-Endogenous overexpression of EC SOD attenuated vasospasm and oxidative stress but failed to reduce neurological deficits after SAH Extracellular O-2(-) likely plays a direct role in the etiology of vasospasm.

Short-inversion time inversion-recovery (STIR) imaging using a 3 tesla system was assessed to reveal the postcommissural fibres (PF) of the fornix, which have rarely been highlighted neuroradiologically in the clinical setting. We studied 27 normal subjects. Sequence parameters were TR/TE/TI 8000/52/ 150 ms. STIR was expected to take advantage of the high signal-to-noise ratio of a high-field system, due to the long repetition time. PF were identifiable in axial and coronal slices in all cases. They were bordered anteriorly and superiorly by the anterior commissure and posteriorly and inferiorly by the mamillary body. Behind the anterior commissure, they ran in an archshaped posterior and inferior course in the hypothalamic nuclei and joined the mamillary body anterolaterally. They usually extended through three 3-mm slices (with 1 mm interslice gap) in anteroposterior and vertical dimensions. Little variation was observed in their course or size. Demonstration of the PF would provide a more detailed correlation of human neuroanatomy to hypothalamic function and individualised understanding of hypothalamic pathology and influence therapy.

Nucleophosmin (NPM) is a major nuclear matrix protein associated with neoplastic: growth in various cell types. We recently suggested that expression of the NPM gene is involved in an increased resistance to UV irradiation in human cells against the cell-killing effects of UV (mainly 254nm wavelength far-ultraviolet ray) [Y. Higuchi, K. Kita, H. Nakanishi, X-L. Wang, S. Sugaya, H. Tanzawa, H. Yamamori, K. Sugita, A. Yamaura, N. Suzuki, Biochem. Biophys. Res. Commun. 248 (1998) 597-602]. In the present study, expression levels of the NPM gene were examined in human cell lines with a high sensitivity to UV cell-killing. Cockayne syndrome patient-derived cell lines, CSAI and CSBI, and the Xeroderma pigmentosum patient-derived cell line, XP20S(SV), XP13KY, XP3KA, XP6BE(SV), XP101OS and XP3BR(SV), have been investigated for their NPM mRNA expression with Northern blotting analysis. All of these UV-sensitive cells demonstrated lower expression levels compared with those of normal fibroblast cells. FF, or an UV-resistant cell line, UHr-10; quite a lower level of expression in XP205(SV) cells after UV irradiation in contrast to a distinguishable increase in the expression in UVr- cells. These results confirmed an intimate correlation between degree of UV sensitivity and expression levels of the NPM gene in human cells. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.