bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of a polymorphism of the ACVRL1 gene with sporadic arteriovenous malformations of the central nervous system
Authors: Simon Matthias , Franke Daniel , Ludwig Michael , Aliashkevich Ales F. , Köster Gertraud , Oldenburg Johannes , Boström Azize , Ziegler Andreas , Schramm Johannes 
Published: January 2008

Object
Important central nervous system (CNS) manifestations in patients with hereditary hemorrhagic telangiectasia (HHT) include arteriovenous malformations (AVMs) and dural arteriovenous fistulas (DAVFs). Hereditary hemorrhagic telangiectasia is caused by germline mutations of two genes: ENG (HHT Type 1) and ACVRL1 (HHT Type 2). The ENG gene variations have been associated with the formation of intracranial aneurysms. The authors studied whether sequence variations in ACVRL1 or ENG are associated with the development of clinically sporadic arteriovenous dysplasias and aneurysms of the CNS.

Methods
The coding sequence (in 44 patients with AVMs and 27 with aneurysms) and the 5′ end and the polyA site (in 53 patients with AVMs) of the ACVRL1 gene were analyzed for sequence variations using direct sequencing and single-strand conformational polymorphism analysis. One ENG and three ACVRL1 gene polymorphisms were genotyped using restriction enzyme–based analysis in 101 patients with sporadic AVMs and DAVFs of the CNS, 79 patients treated for intracranial aneurysms, and 202 control volunteers.
The authors identified a statistically significant association between the IVS3 −35A/T polymorphism in intron 3 of the ACVRL1 gene and the development of AVMs and DAVFs (p = 0.004; odds ratio [OR] 1.73; 95% confidence interval [CI] 1.19–2.51; after adjustments for age and sex), but not aneurysms (crude OR 0.82; 95% CI 0.55–1.18).

Conclusions
The results of this study link ACVRL1 (HHT Type 2 gene) to the formation of the clinically sporadic variants of vascular malformations of the CNS most commonly seen in patients with HHT, that is, AVMs and DAVFs.
Ventriculoperitoneal shunt insertion for the treatment of refractory perilymphatic fistula
Authors: Lollis S. Scott , Weider Dudley J. , Phillips Joseph M. , Roberts David W. 
Published: January 2008

Object
The goal of this study was to provide preliminary data regarding clinical and functional outcome, including postoperative morbidity, related to ventriculoperitoneal (VP) shunt insertion for refractory perilymphatic fistula.

Methods
The authors retrospectively reviewed the records of seven consecutive patients who had undergone VP shunt insertion for medically and surgically refractory perilymphatic fistula between 1996 and 2004. Patients were also contacted by telephone and asked to assess retrospectively their symptomatic improvement, changes in functional status, and changes in work status following shunt placement. Preoperative and postoperative functional statuses were assessed using a standardized instrument. In each patient, preoperative opening pressure was measured via lumbar puncture. Pressures ranged from 160 to 300 mm H2O, with a mean of 241 mm H2O.
All patients reported significant improvement in symptom severity following surgery. Two patients reported complete resolution of symptoms. Three patients were able to resume full-time work. Clinically significant improvement in functional status was noted in six of seven patients. All patients would recommend the procedure to others in a similar situation.

Conclusions
Data in this study suggest that some patients with disabling vertigo, tinnitus, and headache due to perilymphatic fistula, whose conventional medical and surgical therapies have failed to produce a cure, benefit from VP shunt insertion. The authors hypothesize that VP shunt placement blunts intracranial pressure increases, which would cause secondary elevations in perilymphatic fluid pressure. Shunt insertion reduces perilymph leakage into the middle ear and may permit closure of the fistula.
Functions of G protein–coupled receptor kinase interacting protein 1 in human neuronal (NT2N) cells
Authors: Lieu Ann-Shung , Li Jin Zhong , Webb Donna J. , Hankins Gerald R. , Howng Shen-long , Helm Gregory A. 
Published: January 2008

Object
Promotion of the repair and regeneration of damaged adult neurons is a major goal of neurological science. In this study, the effects of G protein–coupled receptor kinase interacting protein 1 (GIT1) overexpression in human neuron cells were tested in human neuronal cells by using an adenoviral vector.

Methods
A recombinant GIT1 and enhanced green fluorescent protein (EGFP) adenoviral vector (AdGIT1) was created by using a standard viral construction procedure. Human neuronal (NT2N) cells, which had been derived from an NT2 human teratocarcinoma cell line, were used in this experiment. Immunocytochemical methods were applied to identify NT2N cells with neural features and to probe the relationship among signaling proteins. Several biological activities were assessed, including neural spine formation, cell migration, and the levels of expression of growth-associated protein–43 (GAP-43) and active Cdc42. The number of cells with spine formation and the number of migrated cells were significantly higher in the AdGIT1-treated group of NT2N cells than in untreated (control) NT2N cells or in AdEGFP-treated NT2N cells. The levels of GAP-43 and active Cdc42 expression were significantly higher in the AdGIT1-treated group than that in the other two cell groups.

Conclusions
The results of this study demonstrate that GIT1 overexpression has the potential to promote neural spine formation and cell migration in human neuronal cells. At the same time, the increased level of GAP-43 in GIT1-overexpressed cells indicates that GIT1 may have the potential to improve growth and regeneration of damaged axons. The GIT1–β-PIX–Cdc42–PAK pathway may play an important role in neuronal outgrowth.
Participation of an abnormality in the transforming growth factor–β signaling pathway in resistance of malignant glioma cells to growth inhibition induced by that factor
Authors: Zhang Lei , Sato Eiji , Amagasaki Kenichi , Nakao Atsuhito , Naganuma Hirofumi 
Published: January 2008

Object
Malignant glioma cells secrete and activate transforming growth factor–β (TGFβ) and are resistant to growth inhibition by that factor. Nevertheless, the mechanism underlying this effect remains poorly understood. In this study, the mechanism of the resistance to growth inhibition induced by TGFβ was investigated.

Methods
The authors examined the expression of downstream components of the TGFβ receptor, including Smad2, Smad3, Smad4, and Smad7, and the effect of TGFβ1 treatment on the phosphorylation of Smad2 and the nuclear translocation of Smad2 and Smad3 by using 10 glioma cell lines and the A549 cell line, which is sensitive to TGFβ-mediated growth inhibition. The expression of two transcriptional corepressor proteins, SnoN and Ski, and the effect of TGFβ1 treatment on the expression of the SnoN protein and the cell cycle regulators p21, p15, cyclin-dependent kinase–4 (CDK4), and cyclin D1 were also examined.
Expression of the Smad2 and Smad3 proteins was lower in the glioma cell lines than in the A549 cell line and in normal astrocytes. In particular, Smad3 expression was low or very low in nine of the 10 malignant glioma cell lines. Expression of Smad4 was low in four glioma cell lines, and expression of the Smad7 protein was similar when compared with protein expression in the A549 cell line and in normal astrocytes. The levels of Smad2 phosphorylation after TGFβ1 treatment were lower in glioma cell lines than in the A549 cell line, except for one glioma cell line. Seven of the 10 glioma cell lines exhibited lower levels of nuclear translocation of Smad2 and Smad3, and two cell lines that expressed very low levels of Smad3 protein showed no nuclear translocation. All glioma cell lines expressed the SnoN protein and its expression was unaltered by treatment with TGFβ1. Three glioma cell lines expressed high levels of the Ski protein. The expression of the p21cip1, p15INK4B, CDK4, and cyclin D1 proteins was not altered by TGFβ1 treatment, except in one cell line that displayed a slight increase in p21 protein. Overall, the expression of the Smad2 and Smad3 proteins was low in the glioma cell lines, the phosphorylation and nuclear translocation of Smad2 and Smad3 were impaired, and the TGFβ receptor signal did not affect the expression of the SnoN, p21, p15, cyclin D1, and CDK4 proteins.

Conclusions
These results suggest that the ability to resist TGFβ-mediated growth inhibition in malignant glioma cells is due to abnormalities in the TGFβ signaling pathway.
Dural involvement in primary extradural meningiomas of the cranial vault
Authors: Bassiouni Hischam , Asgari Siamak , Hübschen Uwe , König Hermann-Josef , Stolke Dietmar 
Published: January 2008

Object
The authors retrospectively analyzed a consecutive series of patients with cranial vault primary extradural meningioma (PEM), with particular regard to the tumor’s dural involvement. The pertinent literature was reviewed.

Methods
Clinical data were retrospectively obtained in a consecutive series of 16 patients treated for a PEM at two institutions between 1992 and 2004. The authors created a classification system based on dural involvement of the tumors.
Nine women and six men (mean age 55 years) presented with a painless, slowly progressive swelling. Preoperative magnetic resonance (MR) imaging revealed dural enhancement at the site of tumor in 11 patients. On surgical inspection, the tumor infiltrated the dura in all but three patients. Histological examination of tissue samples demonstrated tumor infiltration of the dura in all 14 patients in whom the dura had been resected. Three recurrent tumors were observed on follow-up examination during a mean period of 5.8 years (range 1.5–13 years) and required extirpation. In addition to one patient in whom there was histological evidence of malignancy, the other two cases involved two patients in whom no apparent dural involvement was observed during the first surgery. In a review of the literature, the authors found that histological examination showed dural involvement in 22%; the dura was not histologically evaluated in the remaining patients (78%). Postoperative follow-up data exceeding 2 years were only provided in two of the reported cases.

Conclusions
Tumor infiltration of the dura should be assumed in PEMs of the cranial vault, and resection of the dura at the site of craniotomy is recommended to prevent tumor recurrence.
Apoptosis in human glioblastoma cells produced using embryonic stem cell–derived astrocytes expressing tumor necrosis factor–related apoptosis-inducing ligand
Authors: Germano Isabelle M. , Uzzaman Mahmud , Benveniste Ronald J. , Zaurova Milana , Keller Gordon 
Published: January 2008

Object
Embryonic stem (ES) cell–derived astrocytes have several theoretical and practical advantages as gene therapy vectors in the treatment of malignant gliomas. The aim of this study was to test the proapoptotic effects of ES cell–derived astrocytes expressing transgenic tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in human malignant glioma cells.

Methods
Mouse ES cells containing a doxycycline-inducible transgene were engineered with human TRAIL (hTRAIL) and then directed to differentiate into astrocytes. The ES cell-derived–TRAIL-expressing astrocytes were cocultured with human malignant glioma cells. Reverse transcriptase polymerase chain reaction, immunocytochemistry, terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling, and flow cytometry were used to quantify results.
In vitro coculture of ES cell–derived astrocytes expressing hTRAIL with A172 human malignant glioma cells after doxycycline induction caused a significant decrease in cell viability from 85 ± 2% at baseline to 8 ± 2% posttreatment (p < 0.001). Labeling with apoptotic markers showed that cell death occurred by means of apoptosis. A significant increase in apoptotic rate (88 ± 3%) from baseline (4 ± 2%) was found in A172 cells after doxycycline induction (p < 0.005). This effect was superior to the apoptotic rate seen after treatment with recombinant TRAIL (57 ± 2%). A decrease in cell viability and an increase in the apoptotic rate were not found in TRAIL-expressing–ES cell-derived astrocytes after induction with doxycycline or in A172 cells exposed to doxycycline alone.

Conclusions
Engineering of transgenic hTRAIL by using ES cell–derived astrocytes induced apoptosis in human malignant glioma cells while sparing nontumor astrocytes. The apoptotic effects of transgenic hTRAIL are greater than those of recombinant hTRAIL. Analysis of these results suggests that hTRAIL-expressing–ES cell-derived astrocytes should be considered in the development of new in vivo strategies to treat malignant human gliomas.
Survival and early differentiation of human neural stem cells transplanted in a nonhuman primate model of stroke
Authors: Roitberg Ben Z. , Mangubat Erwin , Chen Er-Yun , Sugaya Kiminobu , Thulborn Keith R. , Kordower Jeffrey H. , Pawar Ambarish , Konecny Todd , Emborg Marina E. 
Published: January 2008

Object
Neural cell transplantation has been proposed as a treatment after stroke. The purpose of this study was to establish if human neural stem cells (HNSCs) could survive in the nonhuman primate brain after an ischemic event.

Methods
Three adult cynomolgus monkeys received a unilateral occlusion of the M1 segment of the right middle cerebral artery (MCA). One week later each animal received five magnetic resonance (MR) image–guided stereotactic intracerebral injections of HNSC neurospheres labeled with bromodeoxyuridine (BrdU) in the areas surrounding the ischemic lesion as defined in T1- and T2-weighted images. On the day of transplantation and throughout the study the monkeys received oral cyclosporine (10 mg/kg twice a day), and plasma levels were monitored routinely. The animals were killed at 45, 75, or 105 days after transplantation. Magnetic resonance images revealed a cortical and subcortical infarction in the MCA distribution area. Postmortem morphological brain analyses confirmed the distribution of the infarcted area seen in the MR images, with loss of tissue and necrosis in the ischemic region. Cells that were positive for BrdU were present in the three experimental monkeys, mainly along injection tracks. Double-label immuno-fluorescence for BrdU and βIII-tubulin (a marker of young neurons) revealed colocalization of few HNSCs, most of which were observed outside the immediate injection site. Colocalization with nestin was also observed, indicating an early neural/glial fate.

Conclusions
In a model of stroke in nonhuman primates, HNSCs can survive up to 105 days when transplanted 1 week after an ischemic event and can partly undergo neuronal differentiation.
Magnetic resonance angiography and clinical evaluation of third nerve palsies and posterior communicating artery aneurysms
Authors: Kupersmith Mark J. , Heller Gordon , Cox Terry A. 
Published: January 2008

Object
The authors conducted a study to determine the utility of the clinical profile and magnetic resonance (MR) angiography in evaluating patients with isolated third cranial nerve palsies or posterior communicating artery (PCoA) aneurysms.

Methods
Three-dimensional time-of-flight MR angiography was performed in a consecutive series of patients with isolated acute third cranial nerve palsy not due to a ruptured aneurysm and in patients with unruptured PCoA aneurysms. A neuroradiologist, masked to the identities of the patients, interpreted reformatted maximum intensity projection (MIP) and source images of the PCoAs and aneurysms. The investigators assessed clinical features of oculomotor nerve dysfunction and focal head pain. Cases involving cranial third nerve palsy without aneurysms were classified as Group 1 (no case entailed catheter-based angiography), and cases involving PCoA aneurysms seen on MR angiography (42 cases confirmed by catheter-based angiography) were classified as Group 2.
The mean age of the 73 patients in Group 1 was 60.1 years and that of the 45 patients in Group 2 was 59.1 years (p = 0.37). The pattern and severity of oculomotor (p = 0.61) and lid (p = 0.83) dysfunction and pain frequency (p = 0.2) were similar for the 73 patients with vasculopathy in Group 1 and the 15 symptomatic patients in Group 2. Abnormal pupils were observed in 38% of the patients in Group 1 and 80% of those in Group 2 (p = 0.016). In cases of complete external third nerve palsy, nine of 22 in Group 1 and none of four in Group 2 had normal pupil function. For all patients, source imaging showed 206 PCoAs (85%) and MIP imaging demonstrated 120 PCoAs (49%). Of 48 aneurysms (three bilateral), MIP imaging showed 44 (92%) and source imaging showed 47 (98%). Only a 2-mm aneurysm seen on catheter-based angiography was missed by MR angiography. Symptomatic aneurysms were equal or greater than 4 mm in size.

Conclusions
Only the presence of complete external third nerve palsy and normal pupil function allowed ischemia to be clinically distinguished from a PCoA aneurysm in a patient with isolated third nerve palsy and no subarachnoid hemorrhage. When source image MR angiography demonstrates normal findings, catheter-based angiography need not be performed in these patients, even if pupil function is abnormal.
Effect of subthalamic nucleus lesions in a 6-hydroxydopamine–induced rat parkinsonian model: behavioral and biochemical studies
Authors: Hwang Yong Sup , Shim Insop , Lee Bom Bee , Chang Jin Woo 
Published: January 2008

Object
The purpose of this study was to determine whether subthalamic nucleus (STN) ablation caused by kainic acid can restore dopaminergic neurotransmission and improve motor deficits in a 6-hydroxydopamine (6-OHDA)–induced hemiparkinsonian model.

Methods
The authors investigated behavioral changes in rats displaying parkinsonian symptoms (6-OHDA–lesioned rats) after an STN lesion was created using kainic acid. They also measured levels of dopamine and its metabolites following tissue dissection. The results of this study showed that STN ablation led to behavioral improvement in parkinsonian motor deficits. Increased levels of dopamine were also observed in the striatum and globus pallidus externus (GPE).

Conclusions
The results indicate that creation of an STN lesion in this hemiparkinsonian rat model may counteract some of the neurochemical changes within the striatum and GPE caused by the 6-OHDA, and influence striatal dopaminergic metabolism.
Anatomical analysis of transoral surgical approaches to the clivus
Authors: Balasingam Vijayabalan , Anderson Gregory J. , Gross Neil D. , Cheng Cheng-Mao , Noguchi Akio , Dogan Aclan , McMenomey Sean O. , Delashaw Johnny B. , Andersen Peter E. 
Published: January 2008

Object
The authors conducted a cadaveric anatomical study to quantify and compare the area of surgical exposure and the freedom available for instrument manipulation provided by the following four surgical approaches to the extracranial periclival region: simple transoral (STO), transoral with a palate split (TOPS), Le Fort I osteotomy (LFO), and median labioglossomandibulotomy (MLM).

Methods
Twelve unembalmed cadaveric heads with normal mouth opening capacity were serially dissected. For each approach, quantitation of extracranial periclival exposure and freedom for instrument manipulation (known here as surgical freedom) was accomplished by stereotactic localization. To quantify the extent of extracranial clival exposure obtained, anatomical measurements of the extracranial clivus were performed on 17 dry skull bases.
The values (means ± standard deviations in mm2) for periclival exposure and surgical freedom, respectively, for the surgical approaches studied were as follows: STO = 492 ± 229 and 3164 ± 1900; TOPS = 743 ± 319 and 3478 ± 2363; LFO = 689 ± 248 and 2760 ± 1922; and MLM 1312 ± 384 and 8074 ± 6451. The extent of linear midline clival exposure and the percentage of linear midline clival exposure relative to the total linear midline exposure were as follows, respectively: STO = 0.6 ± 4.9 mm and 7.8 ± 11%; TOPS = 8.9 ± 5.5 mm and 24.2 ± 16.7%; LFO = 32.9 ± 10.2 mm and 85.0 ± 18.7%; and MLM = 2.1 ± 4.4 mm and 6.7 ± 11.1%.

Conclusions
The choice of approach and the resulting degree of complexity and associated morbidity depends on the location of the pathological entity. The authors found that the MLM approach, like the STO approach, provided good exposure of the craniocervical junction but limited exposure of the clivus. The TOPS approach, an approach attended by a lesser risk of morbidity, provided adequate exposure of the extracranial inferior clivus. Maximal exposure of the extracranial clivus proper was provided by the LFO approach.
Gamma Knife surgery–induced meningioma
Authors: Sheehan Jason , Yen Chun PO , Steiner Ladislau 
Published: January 2008

✓Gamma Knife surgery (GKS) is a minimally invasive neurosurgical technique. During the past 30 years, radiosurgery has been performed for a number of intracranial disorders with a generally low incidence of side effects. Although radiation-induced neoplasia following radiotherapy is well documented, there are few reports of this complication following radiosurgery.
The authors are engaged in an ongoing project in which they are studying the delayed adverse effects of radiosurgical changes in 2500 patients with arteriovenous malformations (AVMs) treated within a 30-year period. The cases of 1333 patients treated by the senior author (L.S.) have been reviewed thus far. A subset of 288 patients in this group underwent neuroimaging and participated in clinical follow up for at least 10 years.
The authors report two cases of radiosurgically induced neoplasia. In both cases the patient was treated with GKS for an AVM. Longer than 10 years after GKS, each of the patients was found to have an incidental, uniformly enhancing, dura-based mass lesion near the site of the AVM. These lesions displayed the imaging characteristics of a meningioma. Because in both cases the lesion has displayed no evidence of a mass effect, they continue to be followed using serial neuroimaging. These are the fifth and sixth cases meeting the criteria for radiation-induced neoplasms defined by Cahan, et al., in 1998.
Although radiosurgery is generally considered quite safe, the incidence of radiation-induced neoplasms is not known. These cases and the few others detailed in the literature emphasize the need for long-term neurosurgical follow-up review in patients after radiosurgery.