Intramedullary spinal cord germinoma expresses the protooncogene c-kit.

A 33-year-old woman first noticed numbness in the both lower extremities and the numbness gradually extended up to the thorax. Magnetic resonance (MR) imaging demonstrated a mass with moderate and heterogeneous enhancement and peritumoural intramedullary cysts in the spinal cord at the T-1 to T-3 levels. The tumour was explored partially and intra-operative pathological examination demonstrated the so-called "two-cell pattern" typical of germinoma. The margin of the tumour was not clear. Histological examination showed germinoma with strong c-kit protein expression on the tumour cell surface. Chemotherapy and radiation therapy were given following surgery. Her neurological deficits were improved but not resolved.

Anatomical variations of the ten triangles around the cavernous sinus.

The dimensions of the 10 triangles around the cavernous sinus were measured to define the anatomical characteristics of the triangles and to compare their consistency in shape and area. Twelve tissue blocks containing the bilateral cavernous sinuses and medial two-thirds of the middle cranial fossae were obtained from Japanese adults at autopsy, fixed to a stereotactic frame, and examined with an operative microscope. The dimensions of each triangle were measured with calipers and compared, based on the same point and border. The anteromedial triangle and the superolateral (Parkinson's) triangle were more consistent in shape than the paramedial and oculomotor triangles, but the oculomotor triangle was larger in area than these other triangles. The posteromedial (Kawase's) triangle was more consistent in shape and larger than the anterolateral, lateral, and the posterolateral (Glasscock's) triangles. The anteromedial and superolateral (Parkinson's) triangles are important for the combined epi- and subdural approach to cavernous sinus lesions. The posteromedial (Kawase's) triangle is important for gaining access to the posterior cranial fossa from the middle cranial fossa.

Antisense-mediated reduction in thrombospondin-1 expression reduces cell motility in malignant glioma cells.

Thrombospondin-1 (TSP-1) is a multifunctional matrix protein implicated in cancer cell adhesion, migration, invasion, inhibition of angiogenesis and activation of latent transforming growth factor-beta. The involvement of TSP-1 in the motility of malignant glioma cells was investigated by transfection of TSP-1 complementary deoxyribonucleic acid (cDNA) sense and antisense expression vectors into the glioblastoma cell line T98G-G7 that secretes high amounts of TSP-1. TSP-1 production in the 3 antisense cDNA-transfected clones was significantly reduced to 51%, 43% and 47% compared to the host T98G-G7 cells. Motility of the 3 clones was evaluated by invasion assay and compared to the motility of host T98G-G7 cells and 2 sense-transfected clones. Migration of cells was significantly reduced in the 3 antisense-transfected clones with reduced TSP-1 production to 56%, 61% and 43% compared to the host T98G-G7 cells. The host T98G-G7 and another TSP-1-secreting A172 and YMG5 glioblastoma cells were also treated with a synthetic peptide, WSHWSPWSSCSVTCG, which includes 3 consecutive sequences of the adhesion sites in the TSP-1 molecule and with a control peptide. The synthetic peptide significantly inhibited the migration of T98G-G7 and A172 cells in a dose-related manner. Maximum inhibition of migration was achieved by 100 microg/ml of the peptide and the reduction of cell motility compared to untreated cells was 34.6 % and 53.9 %, respectively. On the other hand, the inhibition of migration by the peptide was minimal in YMG5 cells, which secretes a smaller amount of TSP-1 than T98G-G7 and A172 cells. These results suggest that TSP-1 secreted by malignant glioma cells is involved in the motility of glioma cells.

Participation of thrombospondin-1 in the activation of latent transforming growth factor-beta in malignant glioma cells.

Malignant glioma cells secrete transforming growth factor-beta (TGF-beta) and can activate latent TGF-beta. However, the mechanism of the latent TGF-beta activation has not yet been determined. This study examined whether thrombospondin-1 (TSP-1) secreted by malignant glioma cell lines participates in the activation of latent TGF-beta secreted by the glioma cells. Western blot analysis revealed that TSP-1 was present in both the cell lysates and the culture supernatants of all three malignant glioma cell lines (T98G, A172, and U251). A bioassay for TGF-beta activity revealed that all malignant glioma cell lines used in this study could activate latent TGF-beta by themselves. Latent TGF-beta 1 activation, evaluated by enzyme-linked immunosorbent assay, was inhibited by more than 50% by the addition of neutralizing anti-TSP-1 monoclonal antibody or anti-TSP-1 polyclonal antibody. These results indicate that TSP-1 has a predominant role in the activation of latent TGF-beta in malignant glioma cells.

Effect of a platelet-activating factor receptor antagonist, E5880, on cerebral vasospasm after aneurysmal subarachnoid hemorrhage--open clinical trial to investigate efficacy and safety.

The efficacy and safety of a new platelet-activating factor receptor antagonist, E5880, were investigated for preventing cerebral vasospasm after subarachnoid hemorrhage (SAH) in 71 patients with SAH who underwent surgery for ruptured aneurysms within 3 days. Intravenous E5880 administration (300 micrograms or 1200 micrograms twice daily) was begun within 4 days and continued for 14 days. The incidence of symptomatic vasospasm, low-density area on computed tomography, and angiographic vasospasm was lower than in placebo groups in previous studies. Clinical outcome was favorable compared with previous studies. No clinically important adverse events were observed. These results suggest that E5880 is safe and effective in the treatment of patients with cerebral vasospasm due to SAH.

Molecular cloning and characterization of a cDNA for a novel ethylene receptor, NT-ERS1, of tobacco (Nicotiana tabacum L.).

The cDNA encoding a novel member (NT-ERS1) of ethylene receptor family of tobacco (Nicotiana tabacum L.) was obtained by a combination of RT-PCR and 5'-/3'-RACE cloning. The cDNA was 2,092 nucleotides long and had an open reading frame of 1,911 bp encoding 637 amino acids. The deduced polypeptide lacked a response regulator domain, indicating that the ethylene receptor belongs to an ERS-group. The amino acid sequence was similar to respective members of the tobacco ethylene receptor family: 67.8% to NT-ETR1, 39.1% to NTHK1 and 31.1% to NTHK2. Comparison of amino acid sequence suggested that NT-ERS1 is the counterpart of Nr in the ethylene receptor family of tomato, which belongs to Solanaceae as does tobacco. Northern blot analysis showed that mRNA of NT-ERS1 was present in leaf, shoot and root tissues, and accumulated in leaves treated with exogenous ethylene. A mutated NT-ERS1 cDNA transgene, obtained by introducing one nucleotide substitution into NT-ETR1 cDNA, conferred ethylene insensitivity in tobacco plants, indicating that the translation product of the cDNA actually functioned in the plants.

Long-term follow-up of asymptomatic patients with major artery occlusion: rate of symptomatic change and evaluation of cerebral hemodynamics.

BACKGROUND AND PURPOSE: The natural history of asymptomatic major cerebral artery occlusive disease is unclear. Rate of symptomatic change, appearance of new lesions on MR images, and cerebral hemodynamics were analyzed for patients with asymptomatic major cerebral artery occlusion. METHODS: This prospective study included asymptomatic patients who had occlusive disease between 1992 and 1995. MR imaging and MR angiography were used to detect internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion in 3965 neurologically asymptomatic patients and for follow-up of affected patients for 67 to 105 months (mean, 79 months). Regional cerebral blood flow and cerebrovascular reserve capacity were examined by xenon-enhanced CT at rest and after the administration of acetazolamide, respectively. RESULTS: Eighteen patients had MCA occlusion and 17 had ICA occlusion. During the follow-up period, five patients became symptomatic (four with MCA occlusion and one with ICA occlusion), with no significant difference (P = .332) in the rate of symptomatic change. Among these five patients, new infarction occurred on the ipsilateral side in three patients, contralateral side in one, and bilateral sides in one. New stenotic or occlusive changes occurred in three patients. The patients were divided into groups: group A, without new lesions on MR images (n = 23), and group B, with new lesions (n = 12). There was no significant difference in regional cerebral blood flow value between groups A and B in the whole hemisphere, anterior cerebral artery territory, or MCA territory. There was a significant difference in cerebrovascular reserve capacity between groups A and B between the affected side (P = .00051 and P = .00068, respectively) and the contralateral side (P = .00101 and P = .00115, respectively) for the whole hemisphere and MCA territory, and the difference was more severe on the affected side in both regions. CONCLUSION: These pilot data suggest that asymptomatic MCA occlusion has a worse prognosis than does ICA occlusion. Silent events are common bilaterally. This may be because of hemodynamic factors or perhaps MCA occlusion is a marker for a more progressive type of atherosclerosis. A prospective study involving assessment of hemodynamics and baseline stroke risk factors in patients with MCA occlusion is indicated.

Evaluation of crossed cerebellar diaschisis in 30 patients with major cerebral artery occlusion by means of quantitative I-123 IMP SPECT.

Quantitative crossed cerebellar diaschisis (CCD) and the correlation with a reduction in supratentorial regional cerebral blood flow (rCBF) and cerebrovascular reserve capacity (CVR) were investigated in clinically stable patients with major cerebral artery occlusion by the iodine-123-N-isopropyl-p-iodoamphetamine (I-123 IMP) single photon emission computed tomography (SPECT) method. Thirty patients with major cerebral artery occlusion underwent SPECT by the I-123 IMP autoradiographic method. Regional CBF was measured in the cerebral hemisphere, frontal and parietal lobes, temporo-parietal lobe, and cerebellum both at rest and after administration of acetazolamide. Eighteen of 30 patients (60%) had CCD. CCD was significantly related to magnetic resonance imaging evidence of infarction. Quantitative CCD was 17% and the CVR in the cerebellum was preserved in patients with CCD. There was a significant difference in CBF and CVR between the affected and normal sides in all regions of interest in the patients without CCD [CBF (ml/100 g/min): hemisphere (H), normal side (N): 31.4 +/- 6.8, affected side (A): 27.5 +/- 7.4; p < 0.05. CVR: H, N: 0.56 +/- 0.38, A: 0.42 +/- 0.18; p < 0.01]. CCD is common in patients with major cerebral artery occlusion, and quantitative I-123 IMP SPECT is helpful in detecting CCD in clinically stable patients with occlusion of major cerebral arteries.

Protective effect of FK506 in the reperfusion model after short-term occlusion of middle cerebral artery in the rat: assessment by autoradiography using [125I]PK-11195.

The protective effect of the immunosuppressant agent FK506 in the reperfusion after short-term occlusion of the middle cerebral artery in the rat model was evaluated using [125I]PK-11195 autoradiography. FK506 0.5 mg kg-1 day-1 was administered intramurally to Wistar rats weighing 260-300 g from one day prior to ischemia to seven days after ischemia. Reperfusion was performed after 30 or 60 min occlusion. Infarct area was evaluated by [125I]PK-11195 autoradiography on the seventh day following occlusion. FK506 significantly reduced the infarct area in the caudate nucleus following 30 and 60 min occlusion, but significantly reduced the infarct area in the cortex only following 60 min occlusion. These results suggest that FK506 has a protective effect against reperfusion after short-term occlusion of the middle cerebral artery.

Simultaneous display of MRA and MPR in detecting vascular compression for trigeminal neuralgia or hemifacial spasm: comparison with oblique sagittal views of MRI.

A new technique, simultaneous display of magnetic resonance angiography (MRA) and multiplanar reconstruction (MPR), was performed by a workstation to identify the involved vessels in patients with trigeminal neuralgia (TN) or hemifacial spasm (HFS), and the results were compared with those of oblique sagittal MRI technique. Twelve patients with either HFS or TN were prospectively assessed by simultaneous display of MRA and MPR, and oblique sagittal techniques, to point out the neurovascular compression and to identify the involved vessels. Three-dimensional (3D) time-of-flight (TOF) spoiled gradient-echo (SPGR) images were acquired to create MRA and MPR. Oblique sagittal views were also created and displayed on films. A total of 15 vessels in 12 patients were identified as compressing vessels during surgery. Simultaneous display of MRA and MPR technique pointed out the presence of vessels at and/or around root entry/exit zone (REZ) in all 12 patients, but proper identification by the name of the individual vessel was correct in 13 of 15 cases. However, oblique sagittal technique indicated the presence of vessels at and/or around REZ in 11 patients, but only 8 of 14 vessels were correctly identified. Our new method, simultaneous display of MRA-MPR, facilitated correct identification of the involved vessels compared with the oblique sagittal view method.

Tumoral calcinosis of the lumbar meninges: case report.

OBJECTIVE AND IMPORTANCE: Tumoral calcinosis is a rare disorder of unknown origin. Tumoral calcinosis involving the spine is extremely rare. This is the first case of tumoral calcinosis localized in the dura mater of the lumbar spine. CLINICAL PRESENTATION: This 55-year-old male patient presented with tumoral calcinosis of the lumbar meninges. T1-weighted, sagittal magnetic resonance imaging scans of the lumbar spine revealed a round mass of slightly increased intensity with high-intensity margins, located posterior to the cauda equina at the L4-L5 level. The cauda equina was severely compressed anteriorly. T2-weighted scans revealed that the mass was composed of a high-intensity area with low-intensity margins. T1-weighted magnetic resonance imaging scans obtained after intravenous gadolinium administration revealed some enhancement at the margins. INTERVENTION: The mass lesion was totally resected. Three years after surgery, no recurrence was observed in follow-up magnetic resonance imaging scans. CONCLUSION: Although tumoral calcinosis is a rare cause of mass lesions of the lumbar spine, it should be considered in differential diagnoses. If the lesion can be totally resected, the prognosis should be good, similar to that for general tumoral calcinosis.

Usefulness and pitfalls of intraoperative spinal motor evoked potential recording by direct cortical electrical stimulation.

OBJECTIVE: The aim of this study is to investigate the usefulness and problems with spinal motor evoked potential (MEP) recording, especially the reasons for failed recording. We report our personal experience over the last 8 years in patients with lesions adjacent to the primary motor cortex. METHODS: MEP records of 50 consecutive patients were retrospectively reviewed. MEP was recorded by a catheter electrode inserted in the cervical epidural space. Stimulation electrodes were placed on the cortical surface during surgery. SEP recording was also performed in 29 of 50 patients. RESULTS: MEP was obtained in 40 cases, and SEP was recorded in all 29 cases. The central sulcus was identified in 93% of patients in whom both MEP and SEP were performed, whereas in only 86% of patients who underwent only MEP. The main reason for MEP failure were inadequate exposure of the motor cortex, pre-existing hemiparesis and technical errors. Postoperative deterioration of motor function was closely related to intra-operative MEP changes. CONCLUSION: MEP is a useful tool to determine the motor cortex and to predict postoperative motor function. However, precise pre-operative craniotomy planning and combination with intra-operative SEP is essential to reduce the MEP failure.

Enhancing effect of electric stimulation on cytotoxicity of anticancer agents against rat and human glioma cells.

Electropermeabilization, or electroporation, has been used to deliver genes or drugs into the cytoplasm through micropores in the cell membrane caused by electric stimulation. The cytotoxic effect of a combination of anticancer agents with electric stimulation on rat C6 and human T98G glioma cells was examined in vitro. Electric pulses of 100 microsec square waves (eight cycles at 1 Hz) at various electric fields were delivered to C6 or T98G glioma cell suspensions in combination with several anticancer agents. Cell growth was evaluated 48-72 h after treatment. Measurement of cell lysis by electric stimulation was used to assess the optimum field strength for electroporation. Electric stimulation enhanced significantly the cytotoxicity of bleomycin to both C6 and T98G cells by more than 1000-fold using an electric field of 1750 V/cm for C6 cells and 1000 V/cm for T98G cells. The enhancement disappeared when bleomycin concentration was reduced to 100 pg/ml. The cytotoxicity of carboplatin was weakly but significantly enhanced by electric stimulation when a high dose of carboplatin was used. However, there was no enhancement of the cytotoxicity of nimustine hydrochloride (ACNU), etoposide, and vincristine. These results indicate that the combination of bleomycin and electroporation is the most potent candidate for electrochemotherapy in vivo.

Impairment and restoration of the endothelial blood-brain barrier in the rat cerebral infarction model assessed by expression of endothelial barrier antigen immunoreactivity.

Endothelial barrier antigen (EBA) can be used to detect the blood-brain barrier in the central nervous system of rats. This study investigated the temporal profile of antigen expression in cerebral vessels after infarction and assessed the relationship between re-establishment of this antigen in newly formed vessels and astrocytes around these vessels. Rats were subjected to cerebral ischemia for 2 h by the intraluminal thread method, then killed after 1, 3, 7, 14 and 28 days. Perfusion-fixed paraffin-embedded brains were immunostained for detection of EBA and glial fibrillary acidic protein (GFAP) by the streptavidin-biotin-peroxidase complex method. EBA immunostaining in vessels in the infarcted lesion was reduced at day 1 and had almost disappeared by day 3. Newly formed vessels were found from day 3, but were not stained at day 7. However, these new vessels were weakly stained at day 14 and definitely stained at day 28. GFAP immunostaining was completely negative around these proliferating vessels. The temporal profile of disappearance and re-expression of EBA in cerebral infarcted lesion may be associated with aggravation and improvement of brain edema, although barrier permeability was not explored in this study. The expression of this antigen has no relationship to the formation of astrocyte/endothelial contacts.

Statistical analysis of factors affecting the outcome of patients with ruptured distal anterior cerebral artery aneurysms.

The clinical factors affecting the outcome of patients with ruptured distal anterior cerebral artery (ACA) aneurysms were analyzed using multiple logistic regression analysis. The medical records were reviewed of 52 patients (57 aneurysms) with ruptured distal ACA aneurysms operated on by the same neurosurgeon over 25 years. The standard policy was early surgery for patients in Hunt and Kosnik grades I to IV. Age, sex, Hunt and Kosnik grade, timing of operation, size of aneurysms, number of aneurysms, association of intracerebral haemorrhage (ICH), intraventricular haemorrhage, and azygos ACA, use of temporary clipping, occurrence of premature rupture, and presence of psychiatric change were investigated. Univariant analysis disclosed that clinical grade (P = 0.0006), size of aneurysm (P = 0.005), and size of ICH (P = 0.012) affected the outcome of patients. Multiple logistic regression analysis found that Hunt and Kosnik grade (P = 0.010) and timing of operation (P = 0.033) affected the outcome. There was no significant relationship between long-term outcome and clinical factors, although a close relationship was found with Hunt and Kosnik grade (P = 0.071). Clinical grade and timing of the operation affected the outcome of patients with ruptured distal ACA aneurysms. Patients harboring ICH of over 3 cm diameter in poor grades should also be carefully treated.

Correlation of thrombospondin-1 and transforming growth factor-beta expression with malignancy of glioma.

The expression of thrombospondin-1 (TSP-1) and its role in gliomas have not been well examined. In the present study TSP-1 expression in a panel of malignant glioma cell lines and the expression of TSP-1 and transforming growth factor (TGF-beta) proteins in low-grade and malignant glioma tissues were investigated. Reverse transcription-polymerase chain reaction analysis showed that nine of nine malignant glioma cell lines expressed TSP-1 mRNA, and seven of nine glioma lines expressed TSP-2 mRNA. Production and secretion of TSP-1 were examined in the T98G glioblastoma cell line by western blot analysis. Total TSP-1 protein content in the supernatant was 10 times higher than that in the cell lysate. Secretion of TSP-1 was examined in these glioma cell lines by western blot analysis. All glioma lines secreted significant levels of TSP-1. Bioassay showed that all tumor lines had the capacity to activate latent TGF-beta. Localization of TSP-1, TGF-beta1, -beta2, and -beta3 was examined immunohistochemically in surgically resected glioma tissues, including 11 glioblastomas, six anaplastic astrocytomas, and eight astrocytomas. Most glioblastomas expressed high levels of both TSP-1 and TGF-beta. Anaplastic astrocytomas expressed moderate levels of TSP-1 and TGF-beta. Most malignant gliomas expressed various levels of TGF-beta1, -beta2, and -beta3. The expression of both proteins, however, was weak in low-grade gliomas. Normal brain tissues around the tumors were negatively or very weakly positively stained for TSP-1 and TGF-beta. These results indicate that most malignant glioma cells express TSP-1 in vitro and in vivo, and the expression of TSP-1 and TGF-beta in vivo correlates with the histologic malignancy of glioma. Overexpression of both TSP-1 and TGF-beta may increase the biologic malignancy of malignant gliomas, through generating the active form of TGF-beta in tumor tissues.

Treatment of intradural paraclinoidal aneurysms.

Intradural paraclinoidal aneurysm still presents conceptual confusion and technical surgical problems. The clinical features of 68 consecutive patients with paraclinoidal aneurysms were analyzed. The pterional approach was used in all patients. Subarachnoid hemorrhage (SAH) occurred in 37 patients from the paraclinoidal aneurysm and in 10 patients from another associated aneurysm. Thirty-four of the 37 ruptured paraclinoidal aneurysms were clipped, two blister-like aneurysms required trapping, and one blister-like aneurysm was coated. Thirteen of the 31 unruptured paraclinoidal aneurysms, consisting of 10 with ruptured associated aneurysm, four symptomatic, and 17 incidental, were clipped and 18 were coated. Favorable outcomes were obtained in 38 of 47 patients with SAH and 17 of 21 patients without SAH. Nine unfavorable outcomes in SAH patients were caused by primary brain damage (5), vasospasm (2), cerebral infarction after trapping (1), and pneumonia (1). All four unfavorable outcomes in non-SAH patients were due to surgical procedures for giant aneurysms or associated basilar artery aneurysm. Removal of the anterior clinoid process was performed to secure the proximal neck in 15 patients with large or giant aneurysms. Multiple clips with or without fenestrated clips were required in all giant aneurysms, and exposure of the cervical internal carotid artery (ICA) in 17 giant or large aneurysms. Fenestrated clips were also useful for one small aneurysm projecting posteriorly. A favorable outcome was achieved in 17 of 19 patients undergoing coating. Coating without clipping might be better for some blister-like ICA aneurysms, even if ruptured. Paraclinoidal aneurysms can be clipped with favorable results using these techniques except for giant aneurysms and associated basilar artery aneurysm.

Xenon contrast-enhanced CT imaging of supratentorial hypoperfusion in patients with brain stem infarction.

BACKGROUND AND PURPOSE: The characteristics of hypoperfusion in the supratentorial region of patients with brain stem infarction are unclear. We investigated the relationships between the presence of hypoperfusion and the location, number, and size of the infarcts with xenon contrast-enhanced CT. METHODS: One hundred five patients with brain stem infarction detected by MR imaging underwent xenon contrast-enhanced CT to measure the regional CBF (rCBF) in the frontal, temporal, parietal, and occipital regions and in the putamen and thalamus. A decrease of more than 10% from the mean rCBF value for normal individuals was considered to indicate hypoperfusion. RESULTS: Thirty-six patients had supratentorial hypoperfusion. The mean rCBF values (measured in mL/100 g/minute) were as follows: frontal region, 36.2 +/- 5.1 (-14.8%, n = 28); parietal region, 42.3 +/- 4.7 (-19.1%, n = 29); temporal region, 41.5 +/- 2.8 (-12.6%, n = 12); and thalamus, 50.1 +/- 3.2 (-19.6%, n = 7). Supratentorial hypoperfusion was associated with pontine infarction in 33 patients (upper pons in 15, middle pons in 18, and lower pons in seven), midbrain infarction in two, and medulla infarction in one. Twenty-three patients had infarcts that were larger than 5 mm, and 11 had infarcts that were 2 to 5 mm. Only two had infarcts that were smaller than 2 mm. Seven patients each had one infarct, 13 each had two, and 16 each had three. CONCLUSION: Supratentorial hypoperfusion was associated with larger infarcts, with more infarcts, and with pontine infarction.

Serial angiography and endovascular treatment of dissecting aneurysms of the anterior cerebral and vertebral arteries. Case report.

This 47-year-old man was admitted to the hospital with disturbance of consciousness due to subarachnoid hemorrhage caused by a ruptured dissecting aneurysm of the left anterior cerebral artery (ACA). Conservative treatment resulted in improvement in the patient's consciousness; however, repeated rupture occurred during the chronic stage. Endovascular coil embolization of the parent artery was successful. Serial angiography demonstrated all stages in the development of the aneurysm. Follow-up angiography demonstrated an incidental dissecting aneurysm of the right vertebral artery. This aneurysm was also treated by endovascular embolization. No new neurological deficit appeared during or after the treatment. Multiple dissecting aneurysms are rare, especially those involving both supra- and infratentorial regions. A ruptured dissecting aneurysm of the ACA is also an uncommon vascular disorder. This case shows that rebleeding may occur, even during the chronic stage, and thus appropriate treatment for the prevention of subsequent bleeding is essential. Incidental dissecting aneurysms can be treated using the endovascular technique, but further study is necessary.