Microsomal prostaglandin E synthase-1 is a critical factor in dopaminergic neurodegeneration in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder of uncertain pathogenesis characterized by the loss of nigrostriatal dopaminergic neurons. Although increased production of prostaglandin E2 (PGE2) has been implicated in tissue damage in several pathological settings, the role of microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal enzyme for PGE2 synthesis, in dopaminergic neurodegeneration remains unclear. Here we show that mPGES-1 is up-regulated in the dopaminergic neurons of the substantia nigra of postmortem brain tissue from PD patients and in neurotoxin 6-hydroxydopamine (6-OHDA)-induced PD mice. The expression of mPGES-1 was also up-regulated in cultured dopaminergic neurons stimulated with 6-OHDA. The genetic deletion of mPGES-1 not only abolished 6-OHDA-induced PGE2 production but also inhibited 6-OHDA-induced dopaminergic neurodegeneration both in vitro and in vivo. Nigrostriatal projections, striatal dopamine content, and neurological functions were significantly impaired by 6-OHDA administration in wild-type (WT) mice, but not in mPGES-1 knockout (KO) mice. Furthermore, in cultured primary mesencephalic neurons, addition of PGE2 to compensate for the deficiency of 6-OHDA-induced PGE2 production in mPGES-1 KO neurons recovered 6-OHDA toxicity to almost the same extent as that seen in WT neurons. These results suggest that induction of mPGES-1 enhances 6-OHDA-induced dopaminergic neuronal death through excessive PGE2 production. Thus, mPGES-1 may be a valuable therapeutic target for treatment of PD.

Pyramidal tract abnormalities in the human fetus and infant with trisomy 18 syndrome.

Trisomy 18 or Edwards syndrome is known to exhibit various developmental abnormalities in the central nervous system. We report dominant uncrossed pyramidal tract in trisomy 18 syndrome, based on the postmortem neuropathologic study of eight consecutive autopsied fetuses and infants with trisomy 18 ranging in age from 16 to 39 weeks of gestation, including six males and two females, along with autopsy cases of a stillborn triploid infant with 69XXX and two stillborn infants without chromosomal or neurodevelopmental abnormalities. Five out of eight cases with trisomy 18 showed a larger proportion of uncrossed than crossed pyramidal tract. All of these cases were male, and the anterior corticospinal tract on one side was constantly larger than the contralateral lateral corticospinal tract in the spinal cord on both sides, while the pyramidal tract was hypoplastic in female cases with trisomy 18 and a case with 69XXX. Abnormal pyramidal decussation has been found in cases with posterior fossa malformations such as occipital encephaloceles, Dandy-Walker malformation, Joubert syndrome and Möbius syndrome, but has not been described in cases with trisomy 18. Our data, together with the previous reports describing uncrossed aberrant ipsilateral pyramidal tract in patients with congenital mirror movements caused by DCC gene mutation in chromosome 18, and hypolasia and hyperplasia of the pyramidal tract in X-linked recessive disorders caused by L1CAM and Kal1 gene mutations, respectively, suggest a role of trisomy 18 in association with X-chromosome in the abnormal development of the pyramidal tract.

[Neuropathology of Idiopathic Normal Pressure Hydrocephalus: A Study of Three Autopsy Cases and a Literature Review].

We present neuropathological findings in three autopsy brains from patients diagnosed clinically with idiopathic normal pressure hydrocephalus (iNPH) in Japan; still, specific findings of iNPH remain unclear. Comorbid atherosclerosis and hypertensive microvascular diseases, including arterio- and arteriolosclerosis and ischemic changes in the brain parenchyma, are frequently (65%) observed in autopsy brain tissue from patients with iNPH, which has drawn attention to the clinicopathological similarities and differences between iNPH and Binswanger's disease. Additionally, Aß protein deposition and phosphorylated tau-positive neurofibrillary tangles and neuropil threads are observed in cerebral cortical biopsy specimens obtained during intracranial pressure monitoring or shunt surgery among a subset of patients with iNPH. These findings are as frequent as those reported in autopsy data of the age-matched general population. Alterations in aquaporin-4 expression in the cerebral cortex have also been reported, suggestive of a possible association with altered volume or composition of the interstitial fluid in the microenvironment, particularly in the vicinity of capillaries, or glymphatic system dysfunction and consequent altered interstitial fluid drainage. Greater understanding of the normal anatomical structures and pathways involved in cerebrospinal fluid circulation, particularly in absorption and drainage, in the craniospinal region is essential for better clarity regarding iNPH neuropathology.

Immunohistochemical expression of fibroblast growth factor-2 in developing human cerebrum and epilepsy-associated malformations of cortical development.

To elucidate the biological significance of fibroblast growth factor-2 (FGF-2) expression in epilepsy-associated malformations of cortical development, immunohistochemical expression of FGF-2 was investigated in the developing human cerebral mantles obtained from 30 autopsy cases of fetuses, stillborn infants and children ranging from 12 weeks gestation to 15 years old, and 70 surgically-resected corticectomy specimens from patients with medically intractable epilepsy, including: group I, 12 tubers of tuberous sclerosis; group II, 24 cases of focal cortical dysplasia (FCD) with balloon cells (BC); group III, 11 FCD without BC; group IV, 23 histologically normal-appearing neocortices from patients with Rasmussen encephalitis, cystic-gliotic encephalopathy, temporal lobe epilepsy; and group V, 14 normal-appearing neocortices adjacent to dysplastic lesions from groups I and II. FGF-2 expression was detected in a population of matrix cells and/or neuroblasts within the ventricular zone in fetuses younger than 19 weeks gestation. Nuclei of glioblasts and immature astrocytes were also positive for FGF-2 in cases older than 18 weeks gestation. FGF-2 expression was not detected in immature cortical plate neurons. Astrocytes and ependymal cells were positive for FGF-2 in the postnatal brains. Choroid plexus epithelium was strongly positive for FGF-2 in all cases examined. Among the corticectomy specimens, the cytoplasms and/or nuclei of dysmorphic neurons (DNs) and BCs in groups I and II were variably positive for FGF-2. The proportions of FGF-2 immunoreactive cells (FGF-2-IR%) was significantly higher in groups I (36.9 ± 9.6) and II (45.1 ± 7.0) than in groups III (21.0 ± 5.7), IV (14.4 ± 4.7) and V (24.3 ± 10.3), and that in group V was higher than in group IV (P<0.01). These results indicate that FGF-2 upregulation in DNs and BCs is an important feature common to groups I and II, and suggest that BCs and DNs in these groups represent disturbed gliogenesis from matrix cells and disturbed maturation of cortical neurons from migrating neuroblasts, respectively.

Brainstem neuropathology in a mouse model of Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) is a neurovisceral lipid storage disorder characterized by progressive and widespread neurodegeneration. Although some characteristic symptoms of NPC result from brainstem dysfunction, little information is available about which brainstem structures are affected. In this study, the brainstems of mutant BALB/c NPC1-/- mice with a retroposon insertion in the NPC1 gene were examined for neuropathological changes. In the midbrain, the integrated optic density (IOD) and cell count density of tyrosine-hydroxylase (TH) immunostained neurons were decreased in the substantia nigra. In the pons, TH immunoreactivity in the locus ceruleus (LC) neurons was decreased, while the IOD and the neuronal density of choline acetyltransferase (ChAT)-immunostained neurons in the pedunculopontine tegmental nucleus were preserved. The ChAT immunoreactivity of the hypoglossal nucleus (12N) neurons was not decreased, but Klüver-Barrera staining showed that neuronal density in the nucleus of the solitary tract (NTS) was decreased. Klüver-Barrera and neuronal nuclei (NeuN) staining showed a decrease in neuronal density in the ventral cochlear nucleus, but not in the dorsal cochlear nucleus. Gliosis was widely identified by GFAP staining in various brainstem structures, including the superior and inferior colliculi, the rostral interstitial nucleus of the medial longitudinal fasciculus, the oculomotor complex, the medial geniculate nucleus, the nucleus ambiguus, and the 12N. However, GFAP expression was not augmented in the LC, the cochlear nucleus, or the NTS. These neuropathological findings suggest a basis for the neurological syndromes observed in NPC, such as rigidity, oculomotor symptoms, cataplexy and sleep disturbance, dysphagia, and perceptive deafness.

Putaminal lesion in multiple system atrophy: postmortem MR-pathological correlations.

INTRODUCTION: Posterior putaminal atrophy, putaminal T2-hyper and/or hyposignal changes have been observed in patients with multiple system atrophy (MSA) with parkinsonism. METHODS: Postmortem T2-weighted images were compared with histological findings in seven autopsy-proven cases of putaminal lesions of MSA. All cases were evaluated on 1.5T magnetic resonance imaging (MRI) scanners and three cases were evaluated on 3T scanners. RESULTS: There were three types of putaminal changes: Type 1, mild putaminal atrophy and isointensity; Type 2, putaminal atrophy and diffuse hyperintensity with a hyperintense putaminal rim (HPR); Type 3, putaminal atrophy and iso-or-hypointensity with HPR. The signal intensities of the putamen in Types 1 and 3 were more hypointense on 3T images than on 1.5T images. In Type 1, mild putaminal atrophy showed mild neuronal loss and gliosis and diffuse ferritin deposition. In Types 2 and 3, the areas of putaminal atrophy, severe in the posterior region, showed severe neuronal loss and gliosis, many pigments that were positive for ferritin and Fe (3+) and diffuse ferritin deposition. Although, tissue rarefaction was more severe in Type 2 than in Type 3, pigment deposition was more severe in Type 3. The HPR showed a severe loss of myelin and axons with tissue rarefaction of the external capsule or putaminal rim in Types 2 and 3. CONCLUSION: Posterior putaminal atrophy reflects neuronal loss and gliosis. While putaminal iso-or -hypointensity reflects diffuse ferritin and Fe(3+) deposition, hyperintensity reflects tissue rarefaction. The HPR reflects degeneration of the putaminal lateral margin and/or external capsule. These findings reflect characteristic histological findings of MSA with parkinsonism.

Nestin immunoreactivity of Purkinje cells in Creutzfeldt-Jakob disease.

Nestin, an intermediate filament protein, is mainly expressed in neural progenitor/stem cells in the central nervous system. Recently, we reported that nestin is expressed in Purkinje cells in patients with Creutzfeldt-Jakob disease (CJD). In this study, we examined a total of 19 CJD cerebella to analyze the intensity and pattern of nestin immunoreactivity of Purkinje cells in different pathological stages of degeneration in the cerebellar cortex. The results showed that the Purkinje cells were immunoreactive with nestin regardless of the severity of degenerative cerebellar cortex. Furthermore, we noted several different types of nestin immunoreactivity, indicated by diffuse and fine, coarse, and inclusion-like immunostainings within Purkinje cell bodies as well as dot-like staining outside of the cell bodies. In contrast, on examination of cerebella from non-CJD patients, 6 of 30 cases showed nestin immunoreactivity to a lesser extent. Thus, nestin-positive Purkinje cells are more common in CJD cerebella than in non-CJD cerebella. Although the mechanism of nestin expression in Purkinje cells is not yet understood, we suggest that such nestin-positive Purkinje cells are being reactivated to survive the cell death.

Mixed germ cell tumors with abundant sarcomatous component in the temporal lobe after radiochemotherapy of neurohypophyseal germinoma: a case report.

We report a case of intracranial germ cell tumor that showed pathological changes from neurohypophyseal germinoma to mixed germ cell tumors consisting exclusively of undifferentiated sarcomatous component after radiochemotherapy. Three surgical specimens and autopsied brain from the patient were histologically examined. An initial specimen from the neurohypophyseal tumor was diagnosed as germinoma with a two-cell pattern. Five years later, after repeated radiochemotherapy, the second specimen resected from the right temporal lobe showed mixed germ cell tumors consisting of the three components of germinoma, choriocarcinoma, and immature teratoma. Six months later after intensive radiotherapy, the right temporal tumor recurred and was surgically removed. The histological diagnosis was mixed germ cell tumors with abundant immature teratoma component. The patient died of uncontrollable tumor growth with repeated intratumoral hemorrhages. The autopsied brain showed sarcoma with angionecrosis. This pathological alteration indicated an increase in the sarcomatous component after undergoing various treatments. We discuss the histological changes of intracranial germ cell tumor modified by treatment.

A case of Tolosa-Hunt syndrome affecting both the cavernous sinuses and the hypophysis, and associated with C3 and C4 aneurysms.

BACKGROUND: We describe the first case of Tolosa-Hunt syndrome that is associated with C3 and C4 aneurysms. CASE DESCRIPTION: The patient, a female aged 58 years, had diplopia and right retroorbital pain. Magnetic resonance imaging revealed an enlargement of the hypophysis and bilateral cavernous sinuses, particularly on the right side. Cerebral angiography demonstrated ICA aneurysms of the left C3 and right C4 portions. These symptoms were immediately alleviated after initiation of prednisolone therapy, but recurred after the dose was tapered off. Radiological examination revealed an enlargement of the hypophysis whereas the right C4 aneurysm had decreased in size and no blood flow was apparent in the ipsilateral ophthalmic artery. A biopsy was performed and the results showed a focal inflammatory change. Steroid therapy was represcribed, and after a follow-up period of 10 months without therapy, the patient has been free of symptoms. CONCLUSION: We conclude that bilateral ICA aneurysms might be directly induced by inflammatory infiltration into intracavernous ICAs.

White matter changes in elderly people: MR-pathologic correlations.

Magnetic resonance (MR) imaging features of white matter lesions, often seen in the elderly, are correlated with histologic findings. Dilatation of perivascular spaces is seen, especially in the frontal and/or parietal subcortical white matter; the spaces are less than 3 mm in diameter and have sharp margins with no perifocal abnormality. Old lacunar infarcts are larger than 3 mm in diameter and are irregularly shaped and accompanied by perifocal myelin pallor and gliosis. Periventricular hyperintensity, including cap and rim, histologically shows myelin pallor, dilatation of perivascular spaces, discontinuity of the ependymal lining, and subependymal gliosis. Deep and subcortical white matter hyperintensity reflects myelin pallor and dilatation of perivascular spaces. Diffuse white matter lesion, seen in Binswanger's disease, shows myelin pallor and tissue rarefaction associated with loss of myelin and axons. U-fibers are usually well preserved. Severe arteriosclerosis and arteriolosclerosis are usually seen in the white matter. Knowledge of the pathologic features of incidental changes in white matter helps in understanding MR imaging findings.

Cerebral cortical and white matter lesions in chronic hepatic encephalopathy: MR-pathologic correlations.

We correlated MR images with histologic findings in two autopsy-proven cases of chronic hepatic encephalopathy. Cortical hyperintensities on T2-weighted images histologically revealed pseudolaminar spongy degeneration in the deep layers of the cerebral cortices and hyperintensities in the cerebral white matters showed tissue rarefaction associated with loss of myelin and axons but without reactive astrocytosis. Both lesions were considered to be caused by chronic hepatic encephalopathy.

Application of energy-dispersive X-ray microanalysis on the diagnosis of atypical calcific band keratopathy.

We describe pathological, ultrastructural, and spectrographic analyses of surgically resected cornea from a man with atypical corneal opacification, and discuss the corneal pathogenesis, and the utility of energy-dispersive X-ray microanalysis (EDXA). The histopathologic features of a case presenting with longstanding bilateral corneal clouding are reported, which was difficult to be diagnosed clinically as calcific band keratopathy. The patient underwent keratoplasty on his right eye. Paraffin sections of the host corneal button were subjected to hematoxylin and eosin (H&E). An adjacent section was studied by means of EDXA. Plastic sections were observed under a transmission electron microscope (TEM). H&E staining revealed flattened corneal epithelial cells and disappearing Bowman's membrane accompanied by numerous basophilic granular deposits within the underlying corneal stroma. EDXA demonstrated the elevated peaks of calcium and phosphorus within the area of granular deposits. TEM revealed electron dense material consistent with extracellular calcospherites. Given the patient's past medical and family history, and the serologic test results, the clinical presentation and histological findings were most consistent with calcific band keratopathy associated with preexisting minimal syphilitic keratitis. Extensive histologic studies including EDXA on resected corneal tissue can be helpful for the differential diagnosis and may elucidate the pathogenesis of corneal diseases.

[Hemangioendothelioma of the brain presenting with intracerebral hemorrhage: a case report].

Hemangioendothelioma (HE) is an uncommon vascular tumor that is intermediate in histological appearance between a hemangioma and an angiosarcoma. Presently, it is regarded as endothelial tumors of low-grade or intermediate malignancy. It has been reported in the liver, lung, heart, mediastinum, lymph nodes, extremity, and bone. The occurrence in the brain is extremely rare; only 16 cases have so far been reported. We report a 51-year-old woman who presented with transient visual disturbance and weakness of the left upper limb on April 12th 2003. Computed tomography (CT) revealed a high density mass in the right parietal lobe. In magnetic resonance imaging (MRI), the lesion is hyperintense on TIWI, isointense on T2WI, and no enhancement with gadopentetate dimegliumine. Intratumoral hemorrhage was indicated and preoperative diagnosis was cavernous angioma. The tumor was excised completely on April 28th 2003. Pathologically, the tumor cells resembled endothelial cells, positive immunoreactivity for Factor VIII, and grew in small nests or cords. Postoperative MRI showed complete removal of the tumor. There has been no recurrence for 8 months after the surgery, but we have to follow MRI up for a long time. We discussed intracerebral HE clinically and neuroradiologically.

Bcl-2 expression using retrograde transport of adenoviral vectors inhibits cytochrome c-release and caspase-1 activation in motor neurons of mutant superoxide dismutase 1 (G93A) transgenic mice.

We explored a possible mechanism of the neuro-protective effects of exogenous human Bcl-2 expression on motor neurons of transgenic mice expressing human Cu/Zn superoxide dismutase with a G93A mutation (G93A mice), using retrograde transport and a Cre-loxP recombination system employing adenoviral vectors. We examined the cellular localization of cytochrome c and caspase-1 using immunohistochemical study, in motor neurons of hypoglossal nuclei of G93A mice at 15 weeks after inoculation with the adenoviral vectors, at which time over-expressed exogenous Bcl-2 declined to reach the baseline of intrinsic Bcl-2. We found that a significant number of neurons showed more faint and punctate immunostaining against cytochrome c and significantly less neurons showed immunoreactivity against activated caspase-1, compared with those of mice without inoculation. These results suggest that transient exogenous Bcl-2 expression at the early stage of the disease protects against motor neuronal degeneration in G93A mice by retarding translocation of cytochrome c into the cytosol, and regulating caspase-1 for a substantial period.

Effect on motor neuron survival in mutant SOD1 (G93A) transgenic mice by Bcl-2 expression using retrograde axonal transport of adenoviral vectors.

We investigated the effect of exogenous Bcl-2 on motor neurons in transgenic mice expressing human Cu/Zn superoxide dismutase with a G93A mutation (G93A mice), using adenoviral vectors with a cassette for Bcl-2 (AxCALNLBcl-2) and Cre recombinase (AxCANCre) to express Bcl-2 by Cre-loxP recombination. We were able to detect Bcl-2 in the hypoglossal nuclei of G93A mice for at least 8 weeks after inoculation with AxCALNLBcl-2 followed by inoculation with AxCANCre into the tongue of 10-week-old G93A mice. We examined the morphological changes of motor neurons in the hypoglossal nuclei of each mouse at 25 weeks of age, at which time the G93A mice manifested signs of neural degeneration. We found that the number of motor neurons was significantly higher in the G93A mice with both vectors than in those with AxCALNLBcl-2 alone or without inoculation. Further, we observed an obvious reduction of vacuole formations and reactive astrocytes in and around the hypoglossal nuclei of G93A mice with both vectors. These results suggest that expression of Bcl-2 introduced by our system has a protective effect on degeneration of motor neurons in G93A mice.

White matter lesions in panencephalopathic type of Creutzfeldt-Jakob disease: MR imaging and pathologic correlations.

BACKGROUND AND PURPOSE: A panencephalopathic type of Creutzfeldt-Jakob disease (pCJD) is characterized by the extensive involvement of the cerebral white matter as well as the cerebral gray matter. It has been a point of controversy, however, whether the white matter changes represent primary or secondary degeneration. The aim of this study was to elucidate, by using MR images and histologic examinations, whether the white matter lesions in pCJD are primary or secondary degeneration. METHODS: Serial changes of T2 hyperintensities and histologic findings of six autopsy-proved cases of pCJD were retrospectively analyzed. RESULTS: Serial MR images of brains affected by pCJD revealed that T2 hyperintensities appeared in the cerebral gray matter 2-5 months after onset and in the cerebral white matter around the lateral ventricles approximately 5 months after onset. They rapidly extended to deep and subcortical white matter during the next several months and then to the entire cerebral white matter 10 months after onset. Histologic examination of the white matter lesions revealed spongy changes or tissue rarefaction associated with gemistocytic astrocytosis, which indicates primary involvement of the white matter. At the terminal stages of cases with a longer clinical course, MR images showed T2 hyperintensities in the corticospinal tracts in the internal capsule and brain stem, which histologically disclosed loss of myelin and axons accompanied by fibrillary gliosis that indicates secondary degeneration. CONCLUSION: Cerebral white matter lesions in pCJD were considered to be primary changes of the disease, but the lesions of the corticospinal tracts were secondary to cortical or cerebral or both white matter lesions.

A topographic analysis of the proliferating tumor cells in an autopsied brain with infiltrative thalamic glioma.

Deep-seated gliomas, including thalamic gliomas, have a poor prognosis because of difficulty of accessibility for surgery. In addition, an infiltrative pattern of the tumor is related to a poor prognosis. In this study, the infiltrative/invasive profile of the proliferating tumor cells of a right thalamic glioma was evaluated in an autopsied brain. A 71-year-old man died from extensive infiltration of a right thalamic glioma. The distribution of the proliferating tumor cells at the right thalamic tumor level was represented by the topographic map of MIB-1 labeling indices (LI) on the whole-brain coronal slice, and this map was analyzed with pathological findings and postmortem T2-weighted magnetic resonance imaging (MRI). The highest MIB-1 LI was 24% for the whole autopsy brain at the thalamic tumor level, whereas the MIB-1 LI was 21% for the biopsy sample of the right thalamic glioma. Because this patient survived only 9 months after diagnosis of the tumor as anaplastic astrocytoma, it was confirmed that 21% MIB-1 LI of the biopsy sample was relevant to his prognosis. The topographic map of MIB-1 LI showed that the proliferating tumor cells of the right thalamic glioma invaded the ventricular walls and the contralateral thalamus by the periventricular route, but there was no exophytic extension to the cortex. In conclusion, topographic analysis of the proliferative potential detected by MIB-1 immunostaining provides information on the growth pattern of human glioma.

Attenuation of vascularity by preoperative radiosurgery facilitates total removal of a hypervascular hemangioblastoma at the cerebello-pontine angle: case report.

BACKGROUND: The surgical removal of solid, large, and deep-seated hemangioblastomas remains challenging because it is difficult to control bleeding during the procedure. We used preoperative radiosurgery in a solid, highly vascular hemangioblastoma at the left cerebello-pontine angle and present our angiographic, operative, and histologic findings. CASE DESCRIPTION: A 37-year-old paraplegic woman with multiple hemangioblastomas was re-admitted to our clinic with cerebellar ataxia 6 years after resection of a tumor at the fourth ventricle. A vertebral artery angiogram revealed that the 3.5 cm diameter hemangioblastoma at the left cerebello-pontine angle was highly vascular and fed by the left anterior inferior cerebellar artery and posterior inferior cerebellar artery. Nine months before surgical removal it was treated with stereotactic radiosurgery (gamma knife, margin dose 28 Gy) to inhibit tumor progression and to reduce its vascularity. The tumor was totally removed via the left lateral suboccipital approach; bleeding was well controlled and there were no complications. Pathologic examination of the content of the excised tumor revealed coagulation necrosis with hyaline degeneration of the tumor vessels, resulting in a marked decrease in its vascularity. CONCLUSION: Preoperative radiosurgery led to a marked reduction in the vascularity of this hypervascular hemangioblastoma and was useful for controlling bleeding from the tumor during resection. We succeeded to remove the vascular-rich hemangioblastma after the intentional preoperative radiosurgery. The pathologic changes induced by radiotherapy were confirmed by operative finding.

[A young adult case of spontaneous basilar artery dissection].

We reported a case of basilar artery dissection in a 20-year-old man suffering sudden onset of consciousness disturbance. Brain CT revealed a cerebral infarction of the whole territories of vertebro-basilar artery and his 3DCT showed the occlusion at the base of basilar artery. Autopsy revealed that the subintimal dissection was found at the base of basilar artery and the dissection was spreaded to the distal of bilateral posterior cerebral arteries. The characteristics of his vertebro-basilar artery were small in diameter, thin media and thickened intima. According to these findings, we supposed this rare case of basilar dissection occurred all at once based on a functional abnormality in his small vertebro-basilar arterial wall.

Prognostic significance of sirtuin 2 protein nuclear localization in glioma: an immunohistochemical study.

The sirtuin 2 (SIRT2) protein is a member of the sirtuin family and homologous to Sir2 (silent information regulator 2) of Saccharomyces cerevisiae. To assess the pathobiological significance of SIRT2 protein expression and/or subcellular localization in human glioma, we examined SIRT2 protein expression in human gliomas using a polyclonal anti-SIRT2 antibody and immunohistochemistry. In this study, samples from 23 patients with glioblastoma (GB, grade IV), 8 patients with diffuse astrocytoma (DA, grade II) and 5 healthy individuals were examined. We established a SIRT2 labeling index (SIRT2-LI) that represents the percentage of cells with SIRT2 localized to the nucleus. The mean SIRT2-LI was 65.8±18.6 in GB samples, 41.2±22.8 in DA samples, and 28.6±12.3 in normal control samples. The SIRT2-LI of GB samples was significantly higher than that of normal control samples (P<0.01, Mann-Whitney's U-test) and that of DA samples (P<0.05). Moreover, the SIRT2-LI was positively correlated with malignant progression. Specifically, samples from patients with GB were divided into two groups, low SIRT2-LI (<60%) and high SIRT2-LI (≥60%), and the patients with low SIRT2-LI samples survived significantly longer than patients with high SIRT2-LI samples (P<0.05, Kaplan-Meier method and log-rank test). In conclusion, SIRT2-LI was indicative of glioma malignancy, and it may be predictive of GB patient survival.