bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effect of TAT‐delivered α‐synuclein: relevance of the C‐terminal domain and involvement of HSP70
Authors: Albani Diego , Peverelli Erika , Rametta Raffaela , Batelli Sara , Veschini Lorenzo , Negro Alessandro , Forloni Gianluigi 
Published: September 2004

ABSTRACTα‐Synuclein (α‐syn) is a 140‐amino acid presinaptic protein whose mutations A30P and A53T have been linked to familiar Parkinson’s disease (PD). Many data suggest that α‐syn aggregation is the key event that triggers α‐syn‐mediated neurotoxicity. Nevertheless, other lines of evidence proposed a protective role of α‐syn against oxidative stress (a major feature of PD), even if the exact mechanism of this protective action and the role of the pathogenetic mutations to this respect have not been elucidated yet. To address these points, we developed an in vitro model of oxidative stress by exposing PC12 cells to hydrogen peroxide (H2O2) (150 µM) for 72 h, and we evaluated α‐syn‐mediated protection delivering increasing amounts of α‐syn (wild type [WT] or mutated) inside cells using the fusion proteins TAT‐α‐syn (WT, A30P, and A53T). We found that nanomolar amounts of TAT‐α‐syn‐mediated protected against oxidative stress and other cellular injuries (6‐hydroxydopamine and serum deprivation), whereas micromolar amounts of the fusion proteins were intrinsically toxic to cells. The protective effect was independent from the presence of the mutations A30P and A53T, but no protection occurred when cells were challenged with the proteasome inhibitors lactacystin and MG132. We verified that the protection mechanism required the presence of the C‐terminal domain of α‐syn, as nanomolar amounts of the C‐terminal truncated fusion protein TAT‐α‐syn (WT[1‐97]) failed in preventing H2O2 toxicity. To further characterize the molecular mechanisms at the basis of α‐syn protection, we investigated the possible involvement of the chaperone protein HSP70 that is widely implicated in neuroprotection. We found that, at nanomolar concentrations, TAT‐α‐syn was able to increase HSP70 protein level, whereas at the micromolar scale, TAT‐α‐syn decreased HSP70 at the protein level. These effects on HSP70 were independent from the presence of α‐syn pathogenetic mutations but required the α‐syn C‐terminal domain. The implications for α‐syn‐mediated neurotoxicity and for PD pathogenesis and progression are discussed.
INGAP peptide improves nerve function and enhances regeneration in streptozotocin‐induced diabetic C57BL/6 mice
Authors: Tam Joseph , Rosenberg Lawrence , Maysinger Dusica 
Published: September 2004

ABSTRACTINGAP peptide comprises the core active sequence of Islet Neogenesis Associated Protein (INGAP), a pancreatic cytokine that can induce new islet formation and restore euglycemia in diabetic rodents. The ability of INGAP peptide in vitro to enhance nerve growth from sensory ganglia suggests its potential utility in peripheral nerve disorders. In this study, INGAP peptide was administered alone or in combination with insulin to streptozotocin‐induced diabetic mice exhibiting signs of peripheral neuropathy. Following a 2‐wk treatment period, thermal hypoalgesia in diabetic mice was significantly improved in groups that received INGAP peptide, without development of hyperalgesia. Explanted dorsal root ganglia (DRG) from these groups showed enhanced nerve outgrowth and evidence of increased mitochondrial activity. Western blotting experiments revealed attenuation of neurofilament hyperphosphorylation, up‐regulation of β‐tubulin and actin, and increased phosphorylation of the transcription factor STAT3 in DRG. These findings suggest that INGAP peptide can activate some of the signaling pathways implicated in nerve regeneration in sensory ganglia, thereby providing a means of improvement of nociceptive dysfunction in the peripheral nervous system.
CpG motifs in bacterial DNA delay apoptosis of neutrophil granulocytes
Authors: József Levente , Khreiss Tarek , Filep János G. 
Published: September 2004

ABSTRACTHuman neutrophil granulocytes die rapidly, and their survival is contingent upon rescue from programmed cell death by signals from the environment. We now show that a novel signal for delaying neutrophil apoptosis is unmethylated CpG motifs prevalent in bacterial DNA (CpG‐DNA). Human neutrophils express toll‐like receptor 9 that recognizes these motifs. CpG‐DNA, but not mammalian DNA or methylated bacterial DNA, markedly enhanced neutrophil viability by delaying spontaneous apoptosis. Endosomal maturation of CpG‐DNA is prerequisite for these actions and was coupled to concurrent activation of the extracellular signal‐regulated kinase (ERK) and phosphatidylinositol 3‐kinase/Akt signaling pathways, leading to phosphorylation of BAD at Ser112 and Ser136, respectively, and to prevention of decreases in mitochondrial transmembrane potential, cytochrome c release and caspase‐3 activation. Consistently, pharmacological inhibition of either ERK or phosphatidylinositol 3‐kinase partially reversed these actions of CpG‐DNA; however, they did not produce additive inhibition. Furthermore, intravenous injection of CpG‐DNA (200 μg/kg) into rats evoked slight decreases in blood pressure and induced a modest leukocytosis, whereas it effectively suppressed neutrophil apoptosis as assayed ex vivo. Our results indicate that unmethylated CpG motifs in bacterial DNA promote neutrophil survival by suppressing the apoptotic machinery and may therefore contribute to prolongation and amplification of inflammation.
Double Aneurysms at Distal Basilar Artery: Report of Nine Cases
Authors: Tanaka Yuichiro , Hongo Kazuhiro , Nagashima Hisashi , Tada Tsuyoshi , Kobayashi Shigeaki 
Published: September 2004

ABSTRACT

OBJECTIVE
Double aneurysms at the basilar bifurcation and the basilar artery-superior cerebellar artery (BA-SCA) junction have not been well investigated previously. We analyzed nine patients with double basilar aneurysms to evaluate their radiological characteristics and suitable treatment.

METHODS
Between 1978 and 1999, the incidence of double aneurysms was 5.3% in our 169 consecutive surgical cases of distal BA aneurysms. Seven (77.8%) of the nine patients with double aneurysms had associated aneurysms in the anterior circulation. Open surgery was performed in eight patients and coil embolization in one. The patients' radiological findings, choice of treatment, and surgical results were analyzed retrospectively.

RESULTS
The size of the basilar bifurcation aneurysms ranged from 2 to 8 mm (mean, 4.4 ± 2.0 mm), and the size of the BA-SCA aneurysms ranged from 2 to 12 mm (mean, 5.6 ± 3.6 mm). Diagnosis of double basilar aneurysms was difficult when the basilar trunk had twisted or when size differences between the two aneurysms were apparent. The angle between the posterior cerebral artery and SCA appeared to be wider on the same side as the BA-SCA aneurysms (101 ± 42 degrees) than on the opposite side (26 ± 24 degrees). The P1 segment of the posterior cerebral artery originated in an upright direction from the basilar bifurcation between the two basilar aneurysms in seven patients. The pterional approach was used in eight patients; 14 basilar aneurysms were successfully clipped and 2 were wrapped. Nonstraight clips with short blades were used frequently. Coil embolization of double aneurysms was required twice in one patient because the initial angiogram was misinterpreted as a single aneurysm and its bleb.

CONCLUSION
Measurement of the posterior cerebral artery-SCA angle is a simple method to estimate the presence of BA-SCA aneurysms and to differentiate double aneurysms from a bilocular aneurysm at the basilar bifurcation. The pterional approach is suitable for clipping double basilar aneurysms because anterior circulation aneurysms often coexist, and the upstanding P1 segment is an obstacle in the subtemporal approach to the basilar bifurcation aneurysm. Nonstraight clips with short blades are convenient to avoid conflicting clips in the narrow surgical space.
Catastrophic Football Injuries: 1977–1998
Authors: Cantu Robert C. , Mueller Frederick O. 
Published: September 2004

ABSTRACT
THE PRIMARY PURPOSE of this study was to investigate the occurrence of catastrophic football head and spine injuries, in an attempt to reduce their frequency. We analyzed epidemiological and medical data from 1977 through 1998. Catastrophic football injuries are defined as football injuries that result in death, brain or spinal cord injury, or cranial or spinal fracture. All studied cord injuries involved the cervical region. During the period covered by this study, 118 athletes died as a direct result of participation in the skills of football, 200 football players received a permanent cervical cord injury, and 66 sustained a permanent cerebral injury. Most cervical injuries occurred to defensive players during the act of tackling. The axial loading mechanism of spinal cord injury was identified in 27% of tackling injuries. To further reduce catastrophic injuries, players must stop tackling with the head down and using the head as a battering ram; instead, players should use the shoulder for blocking and tackling. Other recommendations for reducing catastrophic injuries are presented.
Sinonasal Undifferentiated Carcinoma: Case Series and Review of the Literature
Authors: Gorelick Judith , Ross Donald , Marentette Lawrence , Blaivas Mila 
Published: September 2004

ABSTRACT

OBJECTIVE AND IMPORTANCE
We report on four cases of sinonasal undifferentiated carcinoma (SNUC), a relatively newly described clinicopathological entity of the nasal cavity and paranasal sinuses. SNUC tends to present with advanced-stage disease, often with intracranial invasion, and requires an aggressive treatment approach that includes surgical resection. A review of the literature identified several reports of SNUC in pathology and otolaryngology journals since its initial description in 1986, but no report has yet appeared in the neurosurgery literature.

CLINICAL PRESENTATION
Four patients presented with various symptoms related to the nose and/or orbit, including one or more of the following: obstruction, epistaxis, decreased visual acuity, diplopia, and pain. All patients were noted to have masses in the nasal cavity or paranasal sinuses, with or without intracranial extension.

INTERVENTION
All four patients underwent multimodal treatment with chemotherapy, radiotherapy (60–65 Gy), and aggressive surgical resection via a combined bifrontal craniotomy and a subcranial approach to the anterior cranial fossa. Three of four patients died as a result of their disease, an average of 15 months after diagnosis. Only one patient remains alive, although with metastatic intracranial disease, at 24 months after diagnosis.

CONCLUSION
SNUC is a rare neoplasm with a poor prognosis despite an aggressive multimodal approach to treatment. On the basis of our experience, we advocate radical resection as part of the initial combined therapy for patients who present with locally advanced, nonmetastatic disease but we suggest reserving surgery for patients with early brain invasion until there has been a radiographically proven central nervous system response to adjuvant therapy.
Hydrocephalus in Coccidioidal Meningitis: Case Report and Review of the Literature
Authors: Romeo June H. , Rice Louis B. , McQuarrie Irvine G. 
Published: September 2004

ABSTRACT

OBJECTIVE AND IMPORTANCE
Coccidioidomycosis was once confined to the southwest United States and northern Mexico. It has become a larger concern because of the concentration of military bases in these areas, the increasing mobility of populations, and the rising population of immunocompromised persons. Outside endemic areas, the diagnosis is rarely considered. Patients with coccidioidomycosis may develop occult basilar meningitis progressing to communicating hydrocephalus and death.

CLINICAL PRESENTATION
A 60-year-old white man presented with a 1-month history of vertigo, falls, and vomiting. Computed tomography of the head revealed mild hydrocephalus. Lumbar puncture results were remarkable for 1065 mg/dl protein; acid-fast bacillus stain, Gram's stain, and culture results were negative. Postgadolinium magnetic resonance imaging demonstrated enhancement of basilar and cervical meninges, suggesting inflammation, and communicating hydrocephalus. For 48 hours, the patient's level of consciousness decreased progressively.

INTERVENTION
A ventriculoperitoneal shunt was placed, and antifungal agents were initiated on an emergent basis.

CONCLUSION
Coccidioidomycosis should be considered in the differential diagnosis of occult basilar meningitis. The diagnosis is established by the discovery of a high (&gt;1:2) titer of complement-fixing antibody in the cerebrospinal fluid. Communicating hydrocephalus is a common complication of untreated coccidioidal meningitis, and it may develop during appropriate treatment (oral fluconazole, 200–400 mg/d, continued indefinitely). Patients with hydrocephalus and evidence of increased intracranial pressure require a shunt.
Liliequist's Membrane Is a Fold of the Arachnoid Mater: Study Using Sheet Plastination and Scanning Electron Microscopy
Authors: Zhang Ming , An Po-Chung 
Published: September 2004

AbstractOBJECTIVEThe subarachnoid space consists of a number of distinct subarachnoid cisterns. They are separated from each other by trabecular walls, one of which is Liliequist's membrane. The aim of this study was to investigate the anatomic characteristics of Liliequist's membrane.METHODSThe study used a combined approach, consisting of the modified E12 sheet plastination method for 3 adult cadavers and gross anatomic dissection for 35 cadavers, 2 of which were further examined using scanning electron microscopy.RESULTSThe results from this study indicate that 1) Liliequist's membrane is an avascular fold of the arachnoid mater that lacks openings and spreads out laterally, being in direct continuity with the arachnoid mater covering the tentorium; 2) the carotid-chiasmatic walls, which separate the chiasmatic cistern and carotid cisterns and had been considered to be parts of Liliequist's membrane, are vascular and incomplete trabecular walls and should not be considered parts of Liliequist's membrane; and, 3) as a fold of the arachnoid mater, Liliequist's membrane is not directly attached to the temporal lobes and oculomotor nerves.CONCLUSIONLiliequist's membrane is a double-layer fold of the arachnoid mater and has anatomic characteristics different from those of arachnoid trabecular walls.
Near-real-time Guidance Using Intraoperative Magnetic Resonance Imaging for Radical Evacuation of Hypertensive Hematomas in the Basal Ganglia
Authors: Bernays René L. , Kollias Spyros S. , Romanowski Ben , Valavanis Anton , Yonekawa Yasuhiro 
Published: September 2004

Abstract

OBJECTIVE
To report our preliminary clinical experience in treating patients with hypertensive hemorrhage in the basal ganglia using a minimally invasive approach facilitated by intraoperative real-time imaging of an open magnetic resonance imaging (MRI) system and a newly designed cutting suction device.

METHODS
We developed an artifact-free device for use during intraoperative MRI consisting of a guiding base that locks into a burr hole, a side-cutting composite-based cannula connected to a standard aspirator, and a handpiece that allows aspiration strength to be regulated by the surgeon. Thirteen patients with hypertensive bleeding in the basal ganglia were included in the study. Outcome was evaluated by mortality, Glasgow Outcome Scale score, activities of daily living score, and Rankin score at 2 weeks and at a median of 4.2 months after the hemorrhage.

RESULTS
In this group of 13 patients, complete evacuation was achieved in 8 patients (62%) and subtotal evacuation of 75 to 90% of the initial volume in 4 patients (31%); the evacuation was partial in 1 patient (8%). Vascular malformations were preoperatively excluded angiographically. There was no rebleeding during surgery or postoperatively, as demonstrated by immediate postoperative MRI and computed tomography on the 1st postoperative day. Hematomas were evacuated on median Day 4 after the hemorrhage, varying between Day 1 and Day 8; evacuation was performed on Day 21 after the hemorrhage in one patient. Twelve of the 13 patients survived during a median follow-up time of 4.2 months. Neurological function improved in 11 of the 12 patients eligible for assessment. One patient with an additional head injury died 15 days after surgery from pulmonary embolism.

CONCLUSION
This study shows an excellent outcome with regard to mortality and a positive trend regarding neurological outcome for the specific group of patients with hypertensive hematomas in the basal ganglia. This minimally invasive approach is feasible in the open intraoperative MRI in combination with the cutting suction device developed in our institution. Online imaging is extremely helpful for planning, guiding, and real-time monitoring of the procedure.
Radiosurgery for Epilepsy Associated with Cavernous Malformation: Retrospective Study in 49 Patients
Authors: Régis Jean , Bartolomei Fabrice , Kida Yoshihisa , Kobayashi Tatsuya , Vladyka Vilibad , Liscàk Roman , Forster David , Kemeny Andras , Schröttner Oskar , Pendl Gerhard 
Published: September 2004

Abstract

OBJECTIVE
Microsurgical resection of a cavernous malformation (CM) with or without associated cortical resection can provide efficient treatment of drug-resistant associated epilepsy. To explore the potential alternative role of radiosurgery and to evaluate its safety and efficacy for this indication, we conducted a retrospective multicenter study.

METHODS
We retrospectively reviewed the files of patients with long-lasting drug-resistant epilepsy, presumably caused by CM, who were treated by gamma knife (GK) surgery for the control of their epilepsy in five centers (Marseilles, Komaki City, Prague, Graz, and Sheffield). A satisfactory follow-up was available for 49 patients (mean follow-up period, 23.66 ± 13 mo). The mean duration of epilepsy before the GK procedure was 7.5 (±9.3) years. The mean frequency of seizures was 6.9/month (±14). The mean marginal radiation dose was 19.17 Gy ± 4.4 (range, 11.25–36). Among the 49 patients, 17 (35%) had a CM located in or involving a highly functional area.

RESULTS
At the last follow-up examination, 26 patients (53%) were seizure-free (Engel's Class I), including 24 in Class IA (49%) and 2 patients with occasional auras (Class IB, 4%). A highly significant decrease in the number of seizures was achieved in 10 patients (Class IIB, 20%). The remaining 13 patients (26%) showed little or no improvement. The mediotemporal site was associated with a higher risk of failure. One patient bled during the observation period, and another experienced radiation-induced edema with transient aphasia. Postradiosurgery excision was performed in five patients, and a second radiosurgical treatment was carried out in one patient.

CONCLUSION
This series is the first to specifically evaluate the capability of GK surgery to safely and efficiently treat epilepsy associated with CM. Seizure control can be reached when a good electroclinical correlation exists between CM location and epileptogenic zone. Although we do not recommend GK surgery for prevention of bleeding for a CM that has not bled previously, our findings suggest that GK surgery can be proposed for the treatment of epilepsy when the CM is located in a highly functional area.
Neurological Grades of Patients with Poor-grade Subarachnoid Hemorrhage Improve after Short-term Pretreatment
Authors: Suzuki Michiyasu , Otawara Yasunari , Doi Mamoru , Ogasawara Kuniaki , Ogawa Akira 
Published: September 2004

AbstractOBJECTIVEShort-term pretreatment of patients with subarachnoid hemorrhage, but without hematomas causing mass effect, who presented in poor neurological condition at admission was evaluated as a protocol for the selection of candidates for radical surgery.METHODSOne hundred-three patients were pretreated for 12 hours with control of blood pressure and intracranial pressure, using diuretic agents and/or ventricular drainage.RESULTSNeurological improvement was observed for 32 of 47 patients in Grade IV at admission and 23 of 56 patients in Grade V (P &lt; 0.01). Hydrocephalus requiring drainage was more common (P &lt; 0.05) and the interval between onset and admission was shorter (P &lt; 0.01) for the improved group. Clipping surgery was performed for all patients in Grade III or better and for patients in Grade IV who were less than 75 years of age and without systemic complications, i.e., 38 of 47 patients in Grade IV and 16 of 56 patients in Grade V at admission. Good outcomes (defined as moderately disabled or better on the Glasgow Outcome Scale) were achieved by 34 of 38 patients in Grade IV and 10 of 16 patients in Grade V (P &lt; 0.01). The proportion of patients in Grade IV after pretreatment was lower for Grade IV (2 of 38 patients) than for Grade V (9 of 16 patients) (P &lt; 0.00001). However, none of the 49 patients who underwent nonsurgical treatment achieved good outcomes.CONCLUSIONOur protocol may be beneficial for the selection of candidates for radical surgery among patients with subarachnoid hemorrhage but without hematomas who are in poor neurological condition at admission and for the improvement of postoperative outcomes.
Endovascular Treatment of Distally Located Giant Aneurysms
Authors: Ross Ian B. , Weill Alain , Piotin Michel , Moret Jacques 
Published: September 2004

Abstract

OBJECTIVE
Because giant aneurysms (GAs) can be technically difficult to clip, the endovascular approach is becoming increasingly popular. Endovascular treatment of distally located GAs, which often requires parent vessel occlusion, is particularly challenging because limited pathways are available for collateral flow. We aimed to determine the outcomes of endovascular attempts to treat GAs downstream from the circle of Willis.

METHODS
Between 1991 and 1998, 27 patients with 27 distally located very large aneurysms or GAs were evaluated for possible endovascular treatment. Ten underwent selective embolization and 9 were treated with primary parent vessel occlusion, with or without distal bypass. Eight patients could not be treated endovascularly.

RESULTS
Selective embolization resulted in only one cure. Two patients died as a result of subarachnoid hemorrhage during the follow-up period. One coil-treated patient, who underwent subsequent spontaneous parent vessel occlusion, and all nine patients treated primarily with parent vessel occlusion were considered cured after their treatments. Only two patients treated with parent vessel occlusion experienced periprocedural ischemia, which did not result in a major deficit in either case. Of the eight patients who could not be treated endovascularly, one succumbed to surgery, four died while being treated conservatively, and three were lost to follow-up monitoring.

CONCLUSION
Selective aneurysm embolization is usually not curative in these situations. For selected patients, however, endovascular parent vessel occlusion is usually safe and effective in preventing the progression of symptoms and bleeding.