bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medulloblastoma: freedom from relapse longer than 8 years — a therapeutic cure?
Authors: Belza Mark G. , Donaldson Sarah S. , Steinberg Gary K. , Cox Richard S. , Cogen Philip H. 
Published: May 2009

✓ Seventy-seven patients presenting with medulloblastoma between 1958 and 1986 were treated at Stanford University Medical Center and studied retrospectively. Multimodality therapy utilized surgical extirpation followed by megavoltage irradiation. In 15 cases chemotherapy was used as adjunctive treatment. The 10- and 15-year actuarial survival rates were both 41% with an 18-year maximum follow-up period (median 4.75 years). There were no treatment failures after 8 years of tumor-free survival. Gross total removal of tumor was achieved in 22 patients (32%); the surgical mortality rate was 3.9%. No significant difference was noted in the incidence of metastatic disease between shunted and nonshunted patients. The classical form of medulloblastoma was present in 67% of cases while the desmoplastic subtype was found in 16%. Survival rates were best for patients presenting after 1970, for those with desmoplastic tumors, and for patients receiving high-dose irradiation (≥ 5000 cGy) to the posterior fossa. Although early data on freedom from relapse suggested a possible beneficial effect from chemotherapy, long-term follow-up results showed no advantage from this modality of treatment. The patterns of relapse and survival were examined; 64% of relapses occurred within the central nervous system, and Collins' rule was applicable in 83% of cases beyond the period of risk. Although patients treated for recurrent disease could be palliated, none were long-term survivors.
The study data indicate that freedom from relapse beyond 8 years from diagnosis can be considered as a cure in this disease. Long-term follow-up monitoring is essential to determine efficacy of treatment and to assess survival patterns accurately.
“Angioglioma” and the arteriovenous malformationglioma association
Authors: Lombardi Daniela , Scheithauer Bernd W. , Piepgras David , Meyer Fredric B. , Forbes Glenn S. 
Published: May 2009

✓ The term “angioglioma” denotes a highly vascular glioma, most of which are low-grade lesions associated with a favorable prognosis. The authors encountered an example of this pathology, a cystic oligodendroglioma associated with prominent vasculature which both clinically and histologically mimicked an occult arteriovenous malformation (AVM). This case and reports of the association of AVM and glioma prompted a histological review of 1034 surgically resected AVM's, both angiographically occult and visible, among which no oligodendroglial or astrocytic forms of “angioglioma” were found. Eight cases were observed, however, wherein oligodendroglial cells were increased in number within or about the malformation. Two basic histological patterns of oligodendroglial cell excess were seen; one appeared to be malformative in nature with abnormal disposition of oligodendroglial cells being an integral part of the AVM, whereas in the other an apparent increase in cellularity seemed the result of chronic ischemia with condensation of white matter. It appeared that the areas of increased oligodendrocyte content seen in association with AVM are non-neoplastic lesions that exhibit two rather distinct histological patterns of differing origin.
In an effort to determine the frequency of “angioglioma,” the authors examined Tissue Registry data for several glioma groups in which highly vascular examples are prone to occur. Tumors selected for study included 104 cerebellar-type (pilocytic) astrocytomas, 82 oligodendrogliomas, and 51 supratentorial pilocytic astrocytomas. Histological hypervascularity mimicking a vascular malformation (that is, an “angioglioma”) was encountered in 5%, 4%, and 12% of the cases, respectively. Based upon clinical, radiological, and pathological reviews of these cases, as well as a careful review of the literature, it was concluded that 1) “angiogliomas” are neither rare nor represent a distinct clinicopathological entity; 2) in histological but not necessarily angiographic surgical terms, they represent simply highly vascular gliomas, usually of low grade; and 3) the clinicopathological and angiographic features as well as the prognosis of such lesions do not differ from those of similar gliomas without angioma-like vasculature. Finally, “angiogliomas” must not be confused with gliomas of high-grade malignancy which, due to neovascularity, may be highly vascular at angiography and at surgery.
Effects of recombinant human tumor necrosis factor on rodent gliomas and normal brain
Authors: Kiwit Jürgen C. W. , Schmitz Karl-Heinz , Daum Ludwig , Reifenberger Guido , Roosen Norbert 
Published: May 2009

✓ In a study examining the possible therapeutic effects of recombinant human tumor necrosis factor-alpha (rHuTNF-α) on malignant gliomas without expression of tumor necrosis factor (TNF)-receptors, RG-2 glioma cells were tested in vitro as well as in a rat experimental glioma model. A growth inhibition assay revealed no inhibiting effect in vitro up to a concentration of 20 µg/ml rHuTNF-α. Receptor-binding studies showed that RG-2 cells did not present specific receptors for rHuTNF-α. The pharmacokinetics of rHuTNF-α after intravenous injection were studied with respect to serum, tissue, and brain tumor concentrations and showed increased glioma concentrations of (mean ± standard error of the mean) 0.47 ± 0.18 ng TNF/mg brain compared to 0.15 ± 0.05 ng TNF/mg brain in the normal contralateral hemisphere.
No therapeutic effect on solid RG-2 gliomas could be observed after stereotactic injection of 7.3 µg rHuTNF/10 µl buffer solution into the tumor in 10 animals. Immunohistochemical studies after stereotactic injection of rHuTNF-α showed total disappearance of the substance after 24 hours without internalization into tumor cells. Stereotactic injection of 7.3 µg rHuTNF10 µl into normal brain resulted in marked inflammatory response around the injection track, including microvascular thrombosis. These results demonstrate that rHuTNF has neither direct nor indirect cytotoxic activity on RG-2 glioma cells. Furthermore, before clinical use of rHuTNF-α in malignant gliomas, the authors suggest that receptor studies be done in each patient. In receptor-positive patients undergoing treatment with rHuTNF-α, precautions should be taken to prevent local encephalitic reactions.
Induction of transformational changes in normal endothelial cells by cultured human astrocytoma cells
Authors: Silbergeld Daniel L. , Ali-Osman Francis , Winn H. Richard 
Published: May 2009

✓ Endothelial cell proliferation is a significant biological feature of malignant astrocytomas. The ability of the cells of these tumors to elaborate mitogenic angiogenesis factors has been well documented. However, less is known about the transformational effects that neoplastic astrocytes may have on the endothelial cells within malignant astrocytomas. In this study, the hypothesis that humoral factors elaborated by cells derived from malignant astrocytomas induce transformational changes in normal endothelial cells in vitro is investigated. Conditioned medium (CM) was prepared from exponentially growing cultures of a human glioblastoma cell line (UW18) and from two rat brain-tumor cell lines: an anaplastic astrocytoma (R175A) and a glioblastoma with sarcomatous elements (9L). Subconfluent target bovine aortic arch endothelial cells (BAEC's) were exposed for 48 hours to varying concentrations of CM prepared from each of these tumors, and then evaluated for transformational changes. Different molecular weight (MW) fractions of UW18 CM were prepared by molecular ultrafiltration, and each fraction was tested for transforming activity. Transformation endpoints included changes in cellular deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) content and distribution (measured by differential flow cytometry) and changes in de novo DNA synthesis determined by 3H-thymidine incorporation.
Significant changes in the amount and distribution of DNA and RNA were observed in the BAEC's treated with UW18 CM compared to untreated BAEC's. At 10% concentrations of UW18 CM, changes in the RNA profile of target BAEC's were evident, and at 30% concentrations of UW18 CM, an irregular bimodal distribution was well established. Patterns of DNA were also altered in a concentration-dependent manner, with significant aneuploidy developing at UW18 CM concentrations of 20%. The DNA synthesis in BAEC's increased with increasing CM concentrations, up to a maximum of about 250% of control values at 30% concentrations of UW18 CM. The transformational changes induced after exposure of BAEC's to CM prepared from R175A and 9L were significantly less than those observed with UW18 CM. Molecular ultrafiltration was used to prepare UW18 CM fractions with MW cutoffs of less than 10 kD, 10 to 30 kD, and greater than 30 kD. Transformational activity was significant only in CM's with an MW of 10 to 30 kD.
It is concluded that the UW18 human glioblastoma cell line elaborates a soluble factor, or group of factors, with an MW in the 10- to 30-kD range, capable of inducing transformational alterations in target normal endothelial cells, and that such transformation may account for some of the abnormal endothelial cell changes associated with malignant astrocytomas.
Endovascular occlusion of intracranial vessels for curative treatment of unclippable aneurysms: report of 16 cases
Authors: Hodes Jonathan E. , Aymard Armand , Gobin Y. Pierre , Rüfenacht Daniel , Bien Siegfried , Reizine Daniel , Gaston André , Merland Jean Jacques 
Published: May 2009

✓ Among 121 intracerebral aneurysms presenting at one institution between 1984 and 1989, 16 were treated by endovascular means. All 16 lesions were intradural and intracranial, and had failed either surgical or endovascular attempts at selective exclusion with parent vessel preservation. The lesions included four giant middle cerebral artery (MCA) aneurysms, one giant anterior communicating artery aneurysm, six giant posterior cerebral artery aneurysms, one posterior inferior cerebellar artery aneurysm, one giant mid-basilar artery aneurysm, two giant fusiform basilar artery aneurysms, and one dissecting vertebral artery aneurysm. One of the 16 patients failed an MCA test occlusion and was approached surgically after attempted endovascular selective occlusion. Treatment involved pretreatment evaluation of cerebral blood flow followed by a preliminary parent vessel test occlusion under neuroleptic analgesia with vigilant neurological monitoring. If the test occlusion was tolerated, it was immediately followed by permanent occlusion of the parent vessel with either detachable or nondetachable balloon or coils.
The follow-up period ranged from 1 to 8 years. Excellent outcomes were obtained in 12 cases with complete angiographic obliteration of the aneurysm and no new neurological deficits and/or improvement of the pre-embolization symptoms. Four patients died: two related to the procedure, one secondary to rupture of another untreated aneurysm, and the fourth from a postoperative MCA thrombosis after having failed endovascular test occlusion. The angiographic, clinical, and cerebral blood flow criteria for occlusion tolerance are discussed.
Impairment of helper T-cell function and lymphokineactivated killer cytotoxicity following severe head injury
Authors: Quattrocchi Keith B. , Frank Edmund H. , Miller Claramae H. , Amin Asim , Issel Bernardo W. , Wagner Franklin C. 
Published: May 2009

✓ Infection is a major complication of severe head injury, occurring in 50% to 75% of patients who survive to hospitalization. Previous investigations of immune activity following head injury have demonstrated suppression of helper T-cell activation. In this study, the in vitro production of interferon-gamma (INF-γ), interleukin-1 (IL-1), and interleukin-2 (IL-2) was determined in 25 head-injured patients following incubation of peripheral blood lymphocytes (PBL's) with the lymphocyte mitogen phytohemagglutinin (PHA). In order to elucidate the functional status of cellular cytotoxicity, lymphokine-activated killer (LAK) cell cytotoxicity assays were performed both prior to and following incubation of PBL's with IL-2 in five patients with severe head injury.
The production of INF-γ and IL-2 by PHA-stimulated PBL's was maximally depressed within 24 hours of injury (p < 0.001 for INF-γ, p = 0.035 for IL-2) and partially normalized within 21 days of injury. There was no change in the production of IL-1. When comparing the in vitro LAK cell cytotoxicity of PBL's from head-injured patients and normal subjects, there was a significant depression in LAK cell cytotoxicity both prior to (p = 0.010) and following (p < 0.001) incubation of PBL's with IL-2.
The results of this study indicate that IL-2 and INF-γ production, normally required for inducing cell-mediated immunity, is suppressed following severe head injury. The failure of IL-2 to enhance LAK cell cytotoxicity suggests that factors other than decreased IL-2 production, such as inhibitory soluble mediators or suppressor lymphocytes, may be responsible for the reduction in cellular immune activity following severe head injury. These findings may have significant implications in designing clinical studies aimed at reducing the incidence of infection following severe head injury.
Trigeminal neuralgia caused by compression from arteries transfixing the nerve
Authors: Tashiro Haruhiko , Kondo Akinori , Aoyama Ikuhiro , Nin Kiyoshi , Shimotake Katsumi , Nishioka Tatsuya , Ikai Yoshiaki , Takahashi Jun 
Published: May 2009

✓ The authors present three patients with trigeminal neuralgia due to compression by an artery that transfixed the sensory root of the fifth cranial nerve. These cases represented 0.8% of 384 patients with trigeminal neuralgia treated by microvascular decompression at the authors' clinic during the past 12 years. In the remaining 381 cases, the compressing vessels were successfully removed from the trigeminal nerve without much difficulty, for an initial cure rate of 94.3%. In the three cases reported, however, the compressing artery penetrating the nerve could not easily be maneuvered away from the nerve.
In the first two cases, partial rhizotomy perpendicular to the axis of the nerve at the site of arterial transfixion made it possible to separate the artery from the nerve. However, these two patients developed postoperative facial sensory impairment. In the third case, rhizotomy was performed longitudinal to the axis of the nerve at the site of arterial transfixion, making it possible to reposition the artery peripherally beyond the root entry zone of the nerve without causing any postoperative sensory deficits of the face.
No recurrent pain has developed in more than 2½ years since surgery in any of these three cases. When performing microvascular decompression surgery on patients in whom the compressing artery penetrates the nerve, the technique used in our third patient is the procedure of choice.
Origins of Wilder Penfield's surgical technique
Authors: Preul Mark C. , Feindel William 
Published: May 2009

✓ Wilder Penfield left two great legacies: the development of successful surgical treatment of epilepsy and the establishment with his colleagues of the Montreal Neurological Institute as a world-renowned medical center, “dedicated to relief of pain and suffering and to the study of neurology.” That Harvey Cushing's surgical ritual (which stemmed from the painstaking operative methods of Halsted) played a paramount role in the origins of Penfield's surgical technique is revealed by a set of notes and drawings by Penfield during repeated visits in the 1920's to Cushing's clinic at the Peter Bent Brigham Hospital.
Penfield's intellectual approach to the nervous system was derived from his studies with Sherrington, Holmes, Cajal, and Hortega. His eclectic surgical style emerged from his familiarity with the operating techniques of Halsted, Dandy, Horsley, Sargent, Cushing, Frazier, Whipple, Leriche, and Foerster. Penfield's debt to these teachers is documented in his memoirs and in an unpublished report on European neurosurgery which he sent to the Rockefeller Foundation in 1928.
Effect of chemical sympathectomy on cerebral blood flow in rats
Authors: Kobayashi Hidenori , Hayashi Minoru , Kawano Hirokazu , Handa Yuji , Kabuto Masanori , Ide Hisashi 
Published: May 2009

✓ Thirty male Wistar rats, weighing 350 to 400 gm each, received stereotactic injections of 6-hydroxydopamine (300 µg/kg) into the left lateral ventricle. The same amount of saline was injected into a control group of 15 rats. Seven days after this procedure, cerebral blood flow (CBF) was measured by the hydrogen clearance method. A hypertensive condition at a mean arterial pressure of about 160 mm Hg was maintained for 1 hour by intravenous infusion of phenylephrine. In the 6-hydroxydopamine-treated group, CBF increased significantly after the elevation of systemic blood pressure compared with that in the control group, and cerebral autoregulation was impaired. After a 1-hour study, the specific gravity of the cerebral tissue in the treated group significantly decreased; electron microscopic studies at that time revealed brain edema.
It is suggested that depletion of brain noradrenaline levels causes a disturbance in cerebral microvascular tone and renders the cerebral blood vessels more vulnerable to hypertension.
Decussation of hind-limb and fore-limb fibers in the monkey corticospinal tract: relevance to cruciate paralysis
Authors: Pappas Conrad T. E. , Gibson Alan R. , Sonntag Volker K. H. 
Published: May 2009

✓ Cruciate paralysis is a clinical entity in which patients with trauma to the anterior cervicomedullary junction present with weakness of the upper extremity greater than that of the lower extremity. The underlying mechanism of this paralysis is commonly thought to be selective damage affecting the upper-extremity nerve fibers in the pyramidal decussation.
The authors examined the anatomical basis of cruciate paralysis in six New World squirrel monkeys and two Old World cynomolgus monkeys. No evidence for a differential decussation of fore-limb and hind-limb fibers was found. Thus, there is no obvious anatomical explanation for cruciate palsy. The results do suggest two alternative explanations for cruciate paralysis: 1) selective damage to neural areas involving the internuncial cells, the central gray area, and the cuneate nucleus, or 2) injury to the ventral corticospinal tract.
Chronic Antigen Stimulation Alone Is Sufficient to Drive CD8+ T Cell Exhaustion
Authors: Bucks Christine M. , Norton Jillian A. , Boesteanu Alina C. , Mueller Yvonne M. , Katsikis Peter D. 
Published: May 2009

Abstract
The failure of CD8+ T cells to respond to chronic infection has been termed “exhaustion” and describes the condition in which CD8+ T cells exhibit reduced differentiation, proliferation, and effector function. CD8+ T cell exhaustion has been extensively studied in the murine model of chronic infection, lymphocytic choriomeningitis virus (LCMV). Although LCMV-based studies have yielded many interesting findings, they have not allowed for discrimination between the roles of cytokine- and Ag-driven exhaustion. We have created a system of chronic Ag stimulation using murine influenza A virus that leads to exhaustion and functional disability of virus-specific CD8+ T cells, in the absence of high viral titers, sustained proinflammatory cytokine production and lymphocyte infection. Our findings show that Ag alone is sufficient to drive CD8+ T cell impairment, that Ag-driven loss of virus-specific CD8+ T cells is TRAIL mediated, and that removal of Ag reverses exhaustion. Although programmed death 1 was up-regulated on chronic Ag-stimulated CD8+ T cells, it played no role in the exhaustion. These findings provide a novel insight into the mechanisms that control functional exhaustion of CD8+ T cells in chronic infection.
Dexamethasone and FK506 Inhibit Expression of Distinct Subsets of Chemokines in Human Mast Cells
Authors: Kato Atsushi , Chustz Regina T. , Ogasawara Takahisa , Kulka Marianna , Saito Hirohisa , Schleimer Robert P. , Matsumoto Kenji 
Published: May 2009

Abstract
Mast cells produce a large amount of several chemokines after cross-linking of FcεRI and participate in the pathogenesis of allergic diseases. The objective of this study was to comprehensively investigate FcεRI-mediated chemokine induction in human mast cells and the effect of a corticosteroid (dexamethasone) and a calcineurin inhibitor (FK506). Human peripheral blood-derived mast cells were stimulated with anti-IgE Ab in the presence of dexamethasone or FK506. Gene expression profiles were evaluated using GeneChip and confirmed by real-time PCR, and chemokine concentrations were measured by cytometric bead arrays and ELISA. Expression of eight chemokines was significantly induced in mast cells by anti-IgE stimulation. Induction of CCL2, CCL7, CXCL3, and CXCL8 by anti-IgE was significantly inhibited by dexamethasone but was enhanced by FK506. In contrast, induction of CCL1, CCL3, CCL4, and CCL18 was significantly inhibited by FK506 but, with the exception of CCL1, was enhanced by dexamethasone. Combination of dexamethasone and FK506 suppressed production of all chemokines by anti-IgE stimulation. Studies using protease inhibitors indicate that mast cell proteases may degrade several of the chemokines. These results suggest that corticosteroids and calcineurin inhibitors inhibit expression of distinct subsets of chemokines, and a combination of these drugs almost completely suppresses the induction of all chemokine genes in human mast cells in response to FcεRI-dependent stimulation. This implies that a combination of a corticosteroid and a calcineurin inhibitor may be more effective than each single agent for the treatment of allergic diseases in which mast cell-derived chemokines play a major role.
The CysLT1 Ligand Leukotriene D4 Supports α4β1- and α5β1-Mediated Adhesion and Proliferation of CD34+ Hematopoietic Progenitor Cells
Authors: Boehmler Andreas M. , Drost Adriana , Jaggy Lena , Seitz Gabriele , Wiesner Tina , Denzlinger Claudio , Kanz Lothar , Möhle Robert 
Published: May 2009

Abstract
Cytokines and chemokines control hematopoietic stem and progenitor cell (HPC) proliferation and trafficking. However, the role of nonpeptide mediators in the bone marrow microenvironment has remained elusive. Particularly CysLT1, a G protein-coupled receptor recognizing inflammatory mediators of the cysteinyl leukotriene family, is highly expressed in HPCs. We therefore analyzed the effects of its ligands on human CD34+ HPCs. The most potent CysLT1 ligand, LTD4, rapidly and significantly up-regulated α4β1 and α5β1 integrin-dependent adhesion of both primitive and committed HPC. LTD4-triggered adhesion was inhibited by specific CysLT1 antagonists. The effects of other CysLT1 ligands were weak (LTC4) or absent (LTE4). In serum-free liquid cultures supplemented with various hematopoietic cytokines including IL-3, only LTD4 significantly augmented the expansion of HPCs in a dose-dependent manner comparable to that of peptide growth factors. LTC4 and LTE4 were less effective. In CD34+ cell lines and primary HPCs, LTD4 induced phosphorylation of p44/42 ERK/MAPK and focal adhesion kinase-related tyrosine kinase Pyk2, which is linked to integrin activation. Bone marrow stromal cells produced biologically significant amounts of cysteinyl leukotrienes only when hematopoietic cells were absent, suggesting a regulatory feedback mechanism in the hematopoietic microenvironment. In contrast to antagonists of the homing-related G protein-coupled receptor CXCR4, administration of a CysLT1 antagonist failed to induce human CD34+ HPC mobilization in vivo. Our results suggest that cysteinyl leukotriene may contribute to HPC retention and proliferation only when cysteinyl leukotriene levels are increased either systemically during inflammation or locally during marrow aplasia.