bluuebunny/crossref_metadata_2025 huggingface dataset:
The Complex Role of Nitric Oxide in the Pathophysiology of Focal Cerebral Ischemia
Authors: Dalkara Turgay , Moskowitz Michael A.
Published: July 2010

Nitrogen monoxide (NO) has recently emerged as an important mediator of cellular and molecular events which impacts the pathophysiology of cerebral ischemia. Although tempting to ask whether NO is “good or bad” for cerebral ischemia, the question underestimates the complexities of NO chemistry and physiology as well as oversimplifies the pathophysiology of focal cerebral ischemia. Important vascular and neuronal actions of NO have been defined which both enhance tissue survival and mediate cellular injury and death, and these will be reviewed. Strategies which modify NO synthesis and / or metabolism may someday assume therapeutic importance, but not until the tissue compartments generating NO, the activities of the enzymes that are inducibly and constitutively expressed, and the redox state of NO during the stages of ischemic injury, are defined with greater precision. Our knowledge of these processes is rudimentary. This review will summarize the evidence from animal models which supports an emerging role for NO in ischemic pathophysiology. Important aspects of NO synthesis and inhibitors of this process will also be discussed
A Rapid and Sensitive Protocol for Competitive Reverse Transcriptase (cRT) PCR Analysis of Cellular Genes
Authors: Waha Andreas , Watzka Matthias , Koch Anke , Pietsch Torsten , Przkora René , Peters Nils , Wiestler Otmar D. , von Deimling Andreas
Published: July 2010

The specific analysis of gene transcripts is of increasing importance for studies in molecular pathology. Competitive RT‐PCR with mutagenized exogenous competitor templates has evolved as an attractive approach to quantify individual mRNA levels. The generation of exogenous competitor RNAs usually requires mutagenesis and cloning of the mutant fragment into plasmids followed by in vitro transcription. In contrast to primer directed mutagenesis and in vitro transcription, preparation of the mutant fragments is a time consuming procedure. Here we report on a modified semi‐quantitative RT‐PCR protocol to circumvent the laborious cloning of mutant exogenous competitors. Templates for the in vitro transcription are generated in a single PCR reaction with simultaneous addition of a promoter sequence 5 of the forward primer and deletion of 10–20 nucleotides at the opposite end just ahead of the reverse primer binding site. The product of this PCR step serves as template for in vitro transcription to yield exogenous competitor RNA of equal quality and amount as conventional cloning strategies. Total RNA amounts are corrected for by analyzing the expression of different housekeeping genes in the same manner. One of the primers used in the following competitive RT‐PCR reaction is labeled with a fluorescent dye for the analysis of target and exogenous competitor product on an semiautomated sequencer. In the present study, this protocol was employed to analyze the expression of the PTCH, Fas‐receptor, NF‐1, ß2‐microglobulin and GAPD genes in human brain tumors. It will, however, be widely applicable to studies on cellular transcripts in biological specimens.
Disturbance of the Cortical Cholinergic Innervation in Borna Disease Prior to Encephalitis
Authors: Gies U. , Bilzer T. , Stitz L. , Staiger J.F.
Published: July 2010

Rats experimentally infected with the highly neurotropic Borna disease virus (BDV) display a wide variety of dysfunction such as learning deficiencies and behavioral abnormalities. Prior to the onset of encephalitis alterations of one of the major cortical neurotransmitters, acetylcholine, were monitored immunohistochemically by light and electron microscopy of its synthesizing enzyme choline acetyltransferase (ChAT). We found a progressing decrease in the number of ChAT‐positive fibers, starting with discrete changes at day 6 post infection (p.i.) and ending with a nearly complete loss of cholinergic fibers, especially in the hippocampus and neocortex, suggesting a massive disturbance of the cholinergic innervation by day 15 p.i. The fiber pathways (e.g., fimbria‐fornix) connecting the basal forebrain with these target areas in the cortex displayed axon spheroids which are often linked to axonal transport dysfunction. No evidence for significant cellular destruction was seen in the brain, including the cells of origin of these axons in the basal forebrain. We conclude that the motor, mood, learning and memory disabilities in BDV‐infected rats are likely to result, in part, from cortical cholinergic denervation. The present study gives new insights into the pathogenesis of neurological disease caused by a noncytopathogenic virus.
Prenatal Diagnosis of Lysosomal Storage Diseases
Authors: Lake Brian D , Young Elisabeth P , Winchester Bryan G
Published: July 2010

The prenatal diagnosis of lysosomal storage disorders can be achieved, once the diagnosis is confirmed in the index case, by a variety of techniques including analysis of amniotic fluid, asay of enzymic activity in cultured amniotic fluid cells, cultured chorionic villus cells and by direct assay of activity in chorionic villus samples. These studies can be accompanied by ultrastructural observations which give an independent means of diagnosis. In some instances molecular genetic studies for mutation detection or linkage analysis are appropriate for prenatal diagnosis. Pseudodeficiencies of some of the lysosomal enzymes, which cause no clinical problems, can complicate the initial diagnosis particularly in metachromatic leucodystrophy where the pseudodeficiency is more common than the disease itself. Mutation analysis as well as enzyme assay is necessary not only in the index case but also in the parents before the same techniques are applied to a sample for prenatal diagnosis. A large number of lysosomal storage disorders may present as fetal hydrops and the diagnosis can be established at this late stage by fetal blood sampling and examination by microscopy as well as by biochemical assay of the appropriate enzyme or metabolite in amniotic fluid. All prenatal diagnoses in which an affected fetus is indicated should have confirmation of the diagnosis as soon as possible to reassure anxious parents, and to act as audit of the laboratory's competence to undertake prenatal diagnosis. A combined approach to prenatal diagnosis involving bio‐chemical, molecular genetic and morphological studies is recommended.
Afferent Projections to the Mediodorsal and Anterior Thalamic Nuclei in the Cat. Anatomical‐Clinical Correlations.
Authors: Velayos Jose L. , Oliva Manuel , Alfageme Fernando
Published: July 2010

Afferent projections to the mediodorsal and anterior thalamic nuclei in the cat were studied by means of stereotaxic injection of neuronal tracers (horseradish peroxidase and fluorochromes). Acetylcholinesterase reaction was studied, as well as horseradish peroxidase and NADPH‐diaphorase colocation in neuronal bodies which send and receive projections to and from the mediodorsal thalamic nucleus. Based on the connectivity and histochemistry findings, the possibility that prion agents responsible for fatal familial insomnia spread from the mediodorsal and anterior thalamic nuclei through a retrograde pathway is discussed. The possible pathophysiological implication of nitrergic systems in fatal familial insomnia is also considered.
CNS Cell Populations are Protected from Virus‐Induced Pathology by Distinct Arms of the Immune System
Authors: Drescher Kristen M. , Murray Paul D. , David Chella S. , Pease Larry R. , Rodriguez Moses
Published: July 2010

The basis for the distinct patterns of brain pathology in individuals experiencing virus‐induced encephalitis may be related to either the tropism of the virus or the host's response to virus infection of the central nervous system (CNS). In these studies we used Theiler's murine encephalomyelitis virus (TMEV) and a series of mice deficient in various immune system components (α/β T cells, antibody, Class I MHC, and Class II MHC) to examine the hypothesis that discrete populations of CNS cells are protected differentially from virus infection by distinct arms of the immune response. Here we demonstrate that the Class I‐mediated immune response provided more protection from areas of the brain (brainstem, corpus callosum and cerebellum) with abundant white matter as there was significantly more disease in these areas in β2m ‐/‐ (Class I‐deficient) mice as compared to Aβ° (Class II‐deficient) mice. In contrast, the striatum, with an abundance of neurons, was protected from virus‐induced pathology primarily by antibody. In addition, we determined that antibody and α/β T cells provided protection from severe deficits and death during the acute phase of the disease. The data presented here support the hypothesis that distinct immune system components function to protect discrete areas of the CNS from virus‐induced pathology.
Oxidative Stress in Huntington's Disease
Authors: Browne Susan E. , Ferrante Robert J. , Beal M. Flint
Published: July 2010

It has been five years since the elucidation of the genetic mutation underlying the pathogenesis of Huntington's disease (HD) (97), however the precise mechanism of the selective neuronal death it propagates still remains an enigma. Several different etiological processes may play roles, and strong evidence from studies in both humans and animal models suggests the involvement of energy metabolism dysfunction, excitotoxic processes, and oxidative stress. Importantly, the recent development of transgenic mouse models of HD led to the identification of neuronal intranuclear inclusion bodies in affected brain regions in both mouse models and in HD brain, consisting of protein aggregates containing fragments of mutant huntingtin protein. These observations opened new avenues of investigation into possible huntingtin protein interactions and their putative pathogenetic sequelae. Amongst these studies, findings of elevated levels of oxdative damage products such as malondialdehyde, 8‐hydroxy‐deoxyguanosine, 3‐nitrotyrosine and heme oxygenase in areas of degeneration in HD brain, and of increased free radical production in animal models, indicate the involvement of oxidative stress either as a causative event, or as a secondary constituent of the cell death cascade in the disease. Here we review the evidence for oxidative damage and potential mechanisms of neuronal death in HD.
Clonal Origin of Recurrent Meningiomas
Authors: von Deimling Andreas , Larson Jeffrey , Wellenreuther Ruth , Stangl Armin P. , van Velthoven Vera , Warnick Ronald , Tew John , Balko Greg , Menon Anil G.
Published: July 2010

Meningiomas are common intracranial and intraspinal tumors. They are treated primarily by surgical resection. Meningioma recurrence following surgery is frequent despite advances in microneurosurgery. However, it is not clear whether recurrent meningiomas, close or distant to the primary resection site, arise from incomplete resection, dissemination of tumor fragments or from independent tumor growth. In order to address the question of clonality in recurring meningiomas, we examined a series of five patients with a total of 14 tumors for X‐chromosome inactivation in the tumor tissues. Four patients with a total of 11 meningiomas were informative for polymorphisms either in the PGK or the AR genes. All recurrent meningiomas were found to be clonal with respect to the primary lesions. This finding suggests a common molecular pathogenesis of primary meningioma and subsequent recurrences (p < 0.01). In a sixth patient, we analyzed the NF2 gene for mutations in the primary and 5 recurrent meningiomas. All six lesions carried the identical NF2 mutation, strongly indicating a common origin for these tumors. We conclude that recurrent meningiomas usually arise from dissemination of tumor fragments, most likely at the time of the first surgical resection. Our data should alert to the potential of meningioma cells for seeding during surgical procedures.
Fibrillogenesis of Tau: Insights from Tau Missense Mutations in FTDP‐17
Authors: Yen Shu‐Hui , Hutton Michael , DeTure Michael , Ko Li‐Wen , Nacharaju Parimala
Published: July 2010

Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP‐17) is a neurological disorder associated with tau pathology. Tau deposits in FTDP‐17 brains consist of polymerized filaments of hyperphosphorylated tau, the morphology of which is determined by the nature of the tau gene mutation observed in each case. A number of mutations associated with FTDP‐17 have been identified in the 5'splice site of exon 10 and in exons 9–13 of the tau gene. The exon 10 5'splice site mutations disrupt alternative splicing and thus alter the ratio of 4R and 3R Tau isoforms. The majority of Tau missense mutations decrease its ability to bind tubulin and promote microtubule assembly. The extent of reduction varies depending on the site and nature of the mutation. Some Tau missense mutations also have a direct effect on the rate and the extent of tau filament formation. In the presence of polymerization‐inducing agents such as heparin or arachidonic acid, mutant tau forms polymers more efficiently than wild type tau in vitro. Tau mutations affect polymerization at both nucleation and elongation phases. One mutation (R406W) is also known to alter the susceptibility of tau to phosphorylation. Expression of mutant tau in cultured cells changes the cytoskeletal integrity of CHO and COS‐7 cells, but none of the tau transfected cells display tau filament inclusions. These findings suggest involvement of at least two mechanisms in the pathogenesis of FTDP‐17.
CD40L is Critical for Protection from Demyelinating Disease and Development of Spontaneous Remyelination in a Mouse Model of Multiple Sclerosis
Authors: Drescher Kristen M. , Zoecklein Laurie J. , Pavelko Kevin D. , Rivera‐Quinones Cynthia , Hollenbaugh Diane , Rodriguez Moses
Published: July 2010

Theiler's murine encephalomyelitis virus (TMEV) induces acute neuronal disease followed by chronic demyelination in susceptible strains of mice. In this study we examined the role of a limited immune defect (deletion or blocking of CD40 ligand [CD40L]) on the extent of brain disease, susceptibility to demyelination, and the ability of demyelinated mice to spontaneously remyelinate following TMEV infection. We demonstrated that CD40L‐dependent immune responses participate in pathogenesis in the cerebellum and the spinal cord white matter but protect the striatum of susceptible SJL/J mice. In mice on a background resistant to TMEV‐induced demyelination (C57BL/6), the lack of CD40L resulted in increased striatal disease and meningeal inflammation. In addition, CD40L was required to maintain resistance to demyelination and clinical deficits in H‐2b mice. CD40L‐mediated interactions were also necessary for development of protective H‐2b‐restricted cytotoxic T cell responses directed against the VP2 region of TMEV as well as for spontaneous remyelination of the spinal cord white matter. The data presented here demonstrated the critical role of this molecule in both antibody‐ and cell‐mediated protective immune responses in distinct phases of TMEV‐mediated pathology.
Resuscitative Hypothermia Protects the Neonatal Rat Brain from Hypoxic‐Ischemic Injury
Authors: Nedelcu Johann , Klein Michael A. , Aguzzi Adriano , Martin Ernst
Published: July 2010

The effect of 24h of hypothermic recovery on moderate hypoxic‐ischemic brain damage in P7‐rats was investigated for 42d after the insult, using magnetic resonance and histopathology. Occlusion of right common carotid artery and 90min exposure to 8% O2 at 37°C body temperature produced cytotoxic edema of 51 (±11)% brain volume (BV) and depression of brain energy metabolism (PCr/Pi) from 1.43(±0.21) to 0.14(±0.11). During recovery, the body temperature was reduced to 30°C for 24h in 36 animals, but was kept at 37°C in 34 animals. The edema waned upon reoxygenation leaving only the core lesion at 2h, but reappeared reaching a maximal extent of 11 ±8% BV under hypothermia compared to 45(±10)% under normothermia at around 24h. PCr/Pi recovered transiently within 13h and declined again to 1.07(±0.19) under hypothermia and to 0.48(±0.22) under normothermia at around 24h.

Hypothermia led to significant long term brain protection, leaving permanent tissue damage of 12(±6)% BV compared to 35(±12)% BV under normothermia. However, animals with severe initial injury developed large infarctions, despite hypothermic treatment. Even then, the time to develop infarction was significantly prolonged, leaving the opportunity for additional therapeutic intervention.
Preferential Inactivation of the p53 Tumor Suppressor Pathway and Lack of EGFR Amplification Distinguish de novo High Grade Pediatric Astrocytomas from de novo Adult Astrocytomas
Authors: Sung Tammy , Miller Douglas C. , Hayes Roberta L. , Alonso Michelle , Yee Herman , Newcomb Elizabeth W.
Published: July 2010

Classification of high grade astrocytomas of children into genetic subtypes similar to the adult remains to be defined. Here we report an extensive characterization of 29 high grade pediatric astrocytomas, 7 WHO grade III and 22 WHO grade IV, for genetic alterations frequently observed in high grade adult astrocytomas occurring in either the p53/MDM2/p14ARF or Rb/CDK4/p16INK4a tumor suppressor pathways. In addition, we have assessed the contribution of EGFR overexpression and amplification and LOH for chromosome 10, two genetic alterations commonly associated with the development of de novo adult glioblastoma for their roles in the development of de novo astrocytomas of childhood. Our results suggest two major differences in the genetic pathway(s) leading to the formation of de novo high grade astrocytomas in children compared with those of the adult. Our findings show preferential inactivation of the p53 tumor suppressor pathway in > 95% of pediatric astrocytomas versus inactivation of the Rb tumor suppressor pathway in < 25% of the same tumors. In addition, de novo high grade pediatric astrocytomas lack amplification of the EGFR gene compared with EGFR amplification in one‐third of adult glioblastomas. Since drug treatments and gene therapy strategies exploit specific genetic alterations in tumor cells, our findings have important implications for the future development of treatments for high grade pediatric astrocytomas.
The Pathobiology of Myelin Mutants Reveal Novel Biological Functions of the MBP and PLP Genes
Authors: Campagnoni Anthony T. , Skoff Robert P.
Published: July 2010

Substantial biological data indicate that the myelin basic protein (MBP) and myelin proteolipid protein (PLP/DM20) genes produce products with functions beyond that of serving as myelin structural proteins. Much of this evidence comes from studies on naturally‐occurring and man‐made mutations of these genes in mice and other species. This review focuses upon recent evidence showing the existence of other products of these genes that may account for some of these other functions, and recent studies providing evidence for alternative biological functions of PLP/DM20. The MBP and PLP/DM20 genes each encode the classic MBP and PLP isoforms, as well as a second family of proteins that are not involved in myelin structure. The biological roles of these other products of the genes are becoming clarified. The non‐classic MBP gene products appear to be components of transcriptional complexes in the nucleus, and they also may be involved in signaling pathways in T‐cells and in neural cells. The non‐classic PLP/DM20 gene products appear to be components of intracellular transport vesicles in oligodendrocytes. There is evidence for other functions of the classic PLP/DM20 proteins, including a role in neural cell death mechanisms, autocrine and paracrine regulation of oligodendrocytes and neurons, intracellular transport and oligodendrocyte migration.
Paraproteinemic Neuropathies
Authors: Vital Anne
Published: July 2010

The occurrence of a peripheral neuropathy (PN) in association with a monoclonal gammopathy is quite common and suggests that monoclonal proteins may play a pathogenetic role in peripheral nervous system damage. In fact, paraproteinemic PN constitute an heterogeneous group of disorders related to various pathogenetic factors, and the histopathologic features on peripheral nerve biopsies differ from one condition to another. In several well defined disorders, the responsibility of the monoclonal component in the development of the PN has been evidenced. This is the case for most of the PN associated with an IgM monoclonal gammopathy, either a monoclonal gammopathy of undetermined significance (MGUS) or Waldenström's macroglobulinemia. The responsibility of the monoclonal protein in the occurrence of amyloid neuropathy related to multiple myeloma is also recognized. However, most IgG or IgA MGUS, as well as the monoclonal component in POEMS syndrome, have an uncertain causal relationship with the neuropathy. PN associated with monoclonal cryoglobulin (type 1) are occasional and differ from those associated with mixed cryoglobulins (types 2 or 3).
Expression of Death‐related Proteins in Dentate Granule Cells in Human Bacterial Meningitis
Authors: Gerber Joachim , Brück Wolfgang , Stadelmann Christine , Bunkowski Stefanie , Lassmann Hans , Nau Roland
Published: July 2010

Neuronal apoptosis in the dentate gyrus has been observed in animal models of bacterial meningitis and in humans dying in the course of the disease. To evaluate the mechanisms of neuronal cell death, hippocampal sections of 20 patients dying from bacterial meningitis were investigated by immunohistochemistry using antibodies against the proform of caspase‐3 and the active enzyme, bcl‐2, bax and p53. In the dentate granule cell layer, the median density of neurons with an apoptotic morphology was 7.6/mm2 (0–15.6/mm2). The median density of immunoreactive neurons was 2.3/mm2 (procaspase‐3), 0.9/mm2 (activated caspase‐3), 1.8/mm2 (bcl‐2), 1.1/mm2 (bax) and 0.4/mm2 (p53). 80% of neurons immunoreactive for active caspase‐3 had an apoptotic morphology, whereas only 10% of all procaspase‐3 stained neurons showed signs of apoptosis. Apoptotic cell death is present in humans dying in the course of bacterial meningitis in the dentate gyrus of the Formatio hippocampi. Neuronal expression of caspase‐3, bcl‐2 and bax suggests an involvement of these proteins in neuronal death.
The Expression Profile of Myogenic Transcription Factors in Satellite Cells from Denervated Rat Muscle
Authors: Maier; Annette , Zhou; Zhe , Bornemann Antje
Published: July 2010

The muscle‐specific transcription factors of the MyoD family are altered after denervation. In order to determine whether this shift takes place in satellite cells (SC), we investigated the expression pattern of MyoD, myf5, myogenin, and MRF4 in SC. Hindlimb muscles of rats were denervated for 2 days to 4 weeks. SC were isolated, pooled and the transcription of all 4 factors was assessed by RT‐PCR. Protein expression was assessed in histological sections of soleus and anterior tibial (TA) muscles; SC were identified by M‐cadherin. Pooled SC from innervated muscles expressed myf5 mRNA, and very weakly MyoD and myogenin mRNA. MyoD and myogenin protein was found in only few SC. After denervation, pooled SC expressed myf5 mRNA, and very weakly myogenin and MRF4 mRNA. Myogenin protein was found in less than about 10% of the cells, whereas MRF4 protein was absent from SC. We conclude that the presence of myf5 and the absence of MyoD and MRF4 protein in SC after denervation indicated the quiescent state of the cell cycle. A subset of SC has additionally acquired myogenin. SC after denervation might be less easily recruited into the mitotic cycle than SC from normal muscle, rendering regeneration of denervated muscle less efficient than normal muscle.
A Role for Chromosome 9p21 Deletions in the Malignant Progression of Meningiomas and the Prognosis of Anaplastic Meningiomas
Authors: MD Arie Perry , Banerjee Ruma , Lohse Christine M. , Kleinschmidt‐DeMasters Bette K. , Scheithauer Bernd W.
Published: July 2010

Meningiomas display significant variability in terms of recurrence and survival rates, even within tumor grade. Although several recent modifications of the grading system have improved our ability to predict biologic behavior, additional prognostic markers are needed. Inactivation of the cell cycle regulator, p16 (CDKN2A), has recently been observed in a small subset of atypical and the majority of anaplastic meningiomas. To assess the potential clinical utility of this marker, we performed dual‐color FISH on 117 well‐characterized archival meningiomas using paired commercial probes to the chromosome 9 centromeric (CEP9) and p16 (9p21) regions. Benign meningiomas (N=42) were divided into non‐recurring versus recurring groups. Atypical meningiomas (N=52) consisted of proliferative and brain invasive subsets. The 23 anaplastic meningiomas were not further stratified. Deletion of p16 or monosomy 9 was seen in 17% of benign, 52% of atypical, and 74% of anaplastic meningiomas (p<0.001). No statistically significant differences were found among subsets of benign or subsets of atypical meningioma, though there were more recurrences in those with deletion. Despite potential effects on cell cycle regulation, p16 deletions were not restricted to meningiomas with a high proliferative index. Most importantly, p16 deletion was strongly associated with survival in the anaplastic meningioma cohort, with a risk ratio for death of 6.79 (p= 0.016). Conversely, absence of deletion identified a subset of anaplastic meningioma patients (26%) with prolonged survival. We conclude that chromosome 9p21 deletions are associated with malignant progression of meningiomas and poor prognosis in anaplastic meningiomas.
Introduction: Non‐atherosclerotic Cerebrovascular Disorders
Authors: Kalaria Raj N. , Kalimo Hannu
Published: July 2010

Non‐atherosclerotic cerebrovascular disorders are considered to occur less frequently than those caused by embolic or thrombotic disease. Such sporadic disorders resulting from direct effects on the cerebral or peripheral vasculature include hypertensive small vessel disease, vascular inflammatory conditions, aneurysms and arteriovenous malformations. Remarkably, some of these are also inherited in an autosomal dominant manner and appear to entail degeneration or abnormal differentiation of blood vessel wall elements such as smooth muscle, endothelial cells, pericytes and the perivascular nerve plexus. Two intensively investigated examples of these include the cerebral amyloid angiopathies and distinct primary arteriopathies such as CADASIL. The identification of novel genes associated with the hereditary forms of cerebrovascular disorders has been invaluable to understanding of the pathogenesis and management of sporadic disease.
Assessing the Efficacy of Highly Active Antiretroviral Therapy in the Brain
Authors: Kandanearatchi Apsara , Williams Brenda , Everall Ian Paul
Published: July 2010

The devastating effects of HIV infection have been documented for the last 2 decades. Since the 1980s over 60 million people have been infected and at present 40 million people globally are living with HIV (72). HIV infects the central nervous system (CNS) early in the disease process. Indeed, numerous studies document the presence of HIV within the cerebrospinal fluid (CSF) (14,15). Direct infection of the brain by HIV ultimately results in HIV associated dementia (HAD), which (prior to the advent of antiretroviral therapy) affected 20% of patients (48, 55). An increasing number of drugs have been developed to treat this infection and delay the development of AIDS. Current treatment is aimed at inhibiting viral replication, and thus, lowering the viral load. However a subsequent increase in viral load can occur as patients become resistant to drug therapy. In the era of HAART, the incidence of HAD has been reduced, whereas the prevalence rate is increasing as people with HIV survive longer. However, in a study of initial AIDS defining illnesses, the proportion with HIV related dementia did not decline following introduction of HAART (19). In a separate study, no decrease was found in the incidence of dementia per se, although there was a decrease in the incidence of all AIDS‐defining illnesses during this time period (50). It is evident from most studies that since the introduction of HAART, its effect on HAD is not entirely clear, although the majority of findings indicate that it is beneficial. Here we will outline the issues relevant to preventing HAD by HAART.
Pathological Adhesion of Primary Human Schwannoma Cells is Dependent on Altered Expression of Integrins
Authors: Utermark Tamara , Kaempchen Katherine , Hanemann C. Oliver
Published: July 2010

Mutations in the tumor suppressor gene coding for merlin cause Neurofibromatosis type 2 (NF2), all spontaneous schwannomas, and a majority of meningiomas. Merlin links transmembrane proteins to the cytoskeleton. Accordingly, primary human schwannoma cells lacking merlin show an increased number of lamellipodia and filopodia as well as increased cell spreading. We show enhanced adhesion in primary human schwannoma cells and present evidence that this is dependent on the integrin chains α6β1 and α6β4. We further demonstrate that the integrin chains β1 and β4 are upregulated in schwannomas using different complementary methods, and report higher expression of these integrins per schwannoma cell by fluorescence assisted cell sorting (FACS). Finally we report clustering of the integrin chains α6, β1, and β4 on schwannoma cells. Our findings fit well into recent data on the role of merlin in signaling cascades connected to integrins and help explain pathological ensheathment of extracellular matrix or pseudomesaxon formation which is a hallmark of schwannoma histopathology.
BAG1 Over‐expression in Brain Protects Against Stroke
Authors: Kermer Pawel , Digicaylioglu Murat H. , Kaul Marcus , Zapata Juan M. , Krajewska Maryla , Stenner‐Liewen Frank , Takayama Shinichi , Krajewski Stanistan , Lipton Stuart A. , Reed John C.
Published: July 2010

The co‐chaperone BAG1 binds and regulates 70 kDa heat shock proteins (Hsp70/Hsc70) and exhibits cytoprotective activity in cell culture models. Recently, we observed that BAG1 expression is induced during neuronal differentiation in the developing brain. However, the in vivo effects of BAG1 during development and after maturation of the central nervous system have never been examined. We generated transgenic mice over‐expressing BAG1 in neurons. While brain development was essentially normal, cultured cortical neurons from transgenic animals exhibited resistance to glutamate‐induced, apoptotic neuronal death. Moreover, in an in vivo stroke model involving transient middle cerebral artery occlusion, BAG1 transgenic mice demonstrated decreased mortality and substantially reduced infarct volumes compared to wild‐type littermates. Interestingly, brain tissue from BAG1 transgenic mice contained higher levels of neuroprotective Hsp70/Hsc70 protein but not mRNA, suggesting a potential mechanism whereby BAG1 exerts its anti‐apoptotic effects. In summary, BAG1 displays potent neuroprotective activity in vivo against stroke, and therefore represents an interesting target for developing new therapeutic strategies including gene therapy and small‐molecule drugs for reducing brain injury during cerebral ischemia and neurodegenerative diseases.
A 40‐cM Region on Chromosome 14 Plays a Critical Role in the Development of Virus Persistence, Demyelination, Brain Pathology and Neurologic Deficits in a Murine Viral Model of Multiple Sclerosis
Authors: Nakane Shunya , Zoecklein Laurie J. , Gamez Jeffrey D. , Papke Louisa M. , Pavelko Kevin D. , Bureau Jean‐François , Brahic Michel , Pease Larry R. , Rodriguez Moses
Published: July 2010

Theiler's virus persists and induces immunemediated demyelination in susceptible mice and serves as a model of multiple sclerosis. Previously, we identified 4 markers–D14Mit54, D14Mit60, D14Mit61, and D14Mit90–in a 40‐cM region of chromosome 14 that are associated with demyelination in a cross between susceptible DBA/2 and resistant B10.D2 mice. We generated congenic‐inbred mice to examine the contribution of this 40‐cM region to disease. DBA Chr.14B10 mice, containing the chromosomal segment marked by the microsatellite polymorphisms, developed less spinal cord demyelination than did DBA/2 mice. More demyelination was found in the reciprocal congenic mouse B10.D2 Chr.14D2 than in the B10.D2 strain. Introduction of the DBA/2 chromosomal region onto the B10.D2 genetic background resulted in more severe disease in the striatum and cortex relative to B10.D2 mice. The importance of the marked region of chromosome 14 is indicated by the decrease in neurological performance using the Rotarod test during chronic disease in B10.D2 Chr.14D2 mice in comparison to B10.D2 mice. Viral replication was increased in B10.D2 Chr.14D2 mice as determined by quantitative real‐time RT‐PCR. These results indicate that the 40‐cM region on chromosome 14 of DBA/2 mice contributes to viral persistence, subsequent demyelination, and loss of neurological function.
Independent Molecular Development of Metachronous Glioblastomas with Extended Intervening Recurrence‐free Interval
Authors: Martinez Ramon , Schackert Hans‐K. , von Kannen Stephanie , Lichter Peter , Joos Stefan , Schackert Gabriele
Published: July 2010

Two metachronous glioblastomas with different cerebral locations in a 53‐year‐old long‐term survival patient were analyzed by multiple genetic approaches. Using comparative genomic hybridization a different pattern of chromosomal aberrations was observed, with 19 imbalances in the first tumor and only 2 imbalances in the second. Sequence analysis revealed a distinct mutation profile in each tumor, with amino acid substitutions in the p53 and PTEN genes only in the first tumor, ie, p53 in codon 273 (CGT→TGT, Arg→Cys) and PTEN in codon 336 (TAC→TTC, Tyr→Phe). A splicing acceptor site PTEN mutation (IVS8‐2A>G) was observed only in the second GBM. EGFR amplification, mutations of p16INK4a/CDKN2A or p14ARF were not observed. According to the results of p53 mutational analysis and EGFR amplification studies, the first tumor is classified as a type 1 GBM, whereas the alterations in the second one are different from those typically encountered in type 1 or type 2 tumors. In conclusion, our data strongly suggest that the metachronous tumors in this patient are exceptional in that they developed independently from each other. Whether the molecular features of the first glioblastoma are associated with the notably extended recurrence‐free period of 5 years remains to be elucidated.
CGH Pattern of Esthesioneuroblastoma and their Metastases
Authors: Bockmühl Ulrike , You Xuejun , Pacyna‐Gengelbach Manuela , Arps Hartmut , Draf Wolfgang , Petersen Iver
Published: July 2010

Comparative genomic hybridization (CGH) was used to screen 22 esthesioneuroblastomas (ENB) from 12 patients including 12 primary tumors and 10 metastasis/recurrent lesions for chromosomal imbalances being the most extensive study so far. The analysis revealed a characteristic pattern consisting of deletions on chromosomes 3p and overrepresentations on 17q in up to 100% of cases. Other important alterations being detectable in more than 80% of cases were deletions on 1 p, 3p/q, 9p, 10p/q along with overrepresentation on 17p13, 20p and 22q. Particularly striking was the pattern for chromosomes 3, 10 and 17q and 20 being affected almost exclusively by deletions or overrepresentations, respectively. Pronounced overrepresentations suggestive for high copy amplifications were seen on 1p34, 1q23‐q31, 7p21, 7q31, 9p23‐p24, 17q11‐q22, 17q24‐q25, 19, 20p, 20q13 and 22q13. Comparing tumor pairs from the same patient revealed a high concordance indicating clonality and confirming the genetic homogeneity of the tumor entity. The analysis of metastatic/recurrent lesions indicated a higher percentage of pronounced alterations, eg, high copy DNA gains at 1q34‐qter, 7q11, 9p23‐p24, 9q34, 13q33‐q34, 16p13.3, 16p11, 16q23‐q24 and 17p13.The analysis furthermore suggested specific alterations, eg, deletions of chromosome 11 and gains of 1p to be associated with metastasis formation and/or worse prognosis. Our results indicate that ENB is a distinct entity and provides criteria for its genetic distinction from other small round cell tumor types.
The Amyloid Paradox: Amyloid‐β‐Metal Complexes can be Neurotoxic and Neuroprotective
Authors: Bishop Glenda M. , Robinson Stephen R.
Published: July 2010

Senile plaques in the brains of people with Alzheimer disease (AD) are primarily composed of the amyloid‐β (Aβ) peptide and contain substantially elevated levels of iron, copper and zinc. These metals bind to Aβ and have been reported to increase the toxicity of Aβ to cultured neurones. Other reports have demonstrated that Aβ can reduce the neurotoxicity of metal ions, suggesting that the interaction can, under some circumstances, be protective. To investigate these apparently conflicting results, human Aβi‐42 was co‐injected with iron, copper or zinc (at the concentrations found in plaques) into rat cerebral cortex, and the resulting numbers of dying neurones were compared. It was found that Aβ complexed with either iron or zinc was more toxic than Aβ alone. In contrast, Aβ‐copper complexes were not neurotoxic. Surprisingly, we observed that when iron or copper were combined with Aβ, the neurotoxicity of these metals was substantially reduced, suggesting that Aβ may help to limit the toxicity of redox‐active metal ions, thereby assisting the antioxidant defence of the brain. Thus paradoxical effects occur when AP complexes with metal ions, where Aβ‐metal complexes are capable of being neurotoxic and neuroprotective.
A 7‐YEAR‐OLD BOY WITH MIDLINE CEREBELLAR MASS
Authors: Ismail Azzam , Lamont Jayne M. , Tweddle Deborah A. , Pearson Andrew D. , Clifford Steven C. , Ellison David W.
Published: July 2010

CASE OF THE MONTH: ABSTRACT

January 2005. A boy aged 7 years was found to have a tumor arising from the roof of the fourth ventricle. Histopathologically, part of the tumor appeared as a PNET, while neuroglial tissue, striated and smooth muscle, cartilage and small glandular structures were present in other regions. Tumor cells in both primitive and mature elements showed a loss of chromosome 17p accompanied by a gain of 17q, a pattern consistent with the presence of an isochromosome 17q. This abnormality is not characteristic of intracranial germ cell tumors, but is present in over 30% of medulloblastomas. On the basis of the histologic and genetic abnormalities, we propose a diagnosis of PNET with multilineal differentiation.
A Novel Approach to Study Biscuits and Breadsticks Using X‐Ray Computed Tomography
Authors: Frisullo P. , Conte A. , Del Nobile M.A.
Published: July 2010

Abstract:  In this study X‐ray microtomography (μCT) was used for analysis of the microstructure of 6 different types of Italian biscuits and 3 types of Italian breadsticks. Appropriate quantitative 3‐D parameters describing the microstructure were calculated, such as the structure thickness (ST), the object structure volume ratio (OSVR), the degree of anisotropy (DA), and the percentage object volume (POV). Sensory analysis was also performed to discriminate samples on the basis of texture characteristics. A correlation between microstructural data (OSVR for biscuits and OSVR, POV, and DA for breadsticks) and sample crunchiness was also found. Results obtained from the current study showed that analysis at a microscopic level could be useful to the food industry, as the accurate calculation of number, dimension, and distribution of pores in the products could be used to improve the sensorial properties of food. Further study by μCT could be carried out to correlate microstructure to specific ingredients and process conditions to allow obtaining more tailored food.
Ma philosophie de l'accueil
Authors: Branden Jean‐Pierre Vanden
Published: July 2010

Une récente réunion de conservateurs de musées s'est tenue à Bruxelles au cours de laquelle Jean‐Pierre Vanden Branden, ancien président du Comité national belge de l'ICOM et conservateur de la maison d'Érasme et du béguinage d'Anderlecht‐lès‐Bruxelles, analysa l'importance de certains principes de la profession. Il fit notamment le point sur sa longue expérience de conservateur de musée qui accueille personnellement les groupes depuis plus de trente ans.
Building Canada's National Museum of Man: an interprofessional dialogue
Authors: MacDonald George , Cardinal Douglas J.
Published: July 2010

Early in 1982 the Government of Canada announced the creation of a special crown corporation, the Canada Museums Construction Corporation (CMCC), to design and erect new buildings for two museums within the National Museums of Canada: the National Gallery of Canada and the National Museum of Man. After extensive consultation, in particular with the staffs of the two museums and the Board of Trustees of the National Museums, CMCC made recommendations on sites and architects, which the government approved early in 1983. The architect chosen for the National Museum of Man, to work in collaboration with the Montreal firm of Tétreault, Parent, Languedoc, was Douglas Cardinal of Edmonton, Alberta. Most of Cardinal's highly individual and sculptural buildings, with serpentine walls, are in his native province—in smaller communities such as Grande Prairie, Red Deer and Ponoka. It is probably not unimportant, since the Museum of Man is devoted to the history and life of mankind in Canada, that Cardinal is a metis; his maternal grandmother was a Black Foot. The Director of the National Museum of Man since July 1983 has been Dr George MacDonald, who has worked at that museum for twenty‐one years and who was for eight years Chief of its Archaeology Division. Responding to a request from Museum, Dr Jean Sutherland Boggs, former Chairman of the CMCC, organized a discussion which took place in November 1984.
L'Allemagne au sud du Brésil
Authors: Spinelli Teniza Iara de Freitas
Published: July 2010

Le Musée historique Visconde de la ville de São Leopoldo permet de découvrir certaines des caractéristiques introduites par les immigrants allemands venus s'installer dans le sud du Brésil, où ils ont, notamment, apportê leur savoir‐faire d'artisans, leur solide niveau d'instruction et leur goût pour le chant et le sport. L'auteur de cet article, membre du Comité brésilien du Conseil international des musées et du Conseil fédéral de muséologie, occupe les fonctions de coordonnateur des musées au Secrétariat de la culture de l'État du Rio Grande do Sul et celles de directeur du Musée anthropologique de ce même État.
Peintures: le contrôle climatique passif des vitrines
Authors: Bosshard Emil
Published: July 2010

En ce qui concerne les techniques muséologiques, on suppose généralement que «plus c'est complexe, mieux c'est». Le présent article donne à penser que, même dans un pays de très haute technicité comme la Suisse, cette assertion n'est pas forcément justifiée. Après avoir été restaurateur adjoint au Rijksmuseum d'Amsterdam et conservateur des beaux‐arts à l'Institut canadien de conservation d'Ottawa, l'auteur a dirigé le Département de conservation à l'Institut suisse pour la recherche dans le domaine artistique (Swiss Institute for Art Research), à Zurich; depuis 1985, il est responsable de la conservation de la collection Thyssen‐Bornemisza, à Lugano.
La démarche audiovisuelle: oui, mais…
Authors: Schuessler Jennifer
Published: July 2010

Beaucoup de musées pauvres de par le monde rêvent d'en être équipés, alors que certains de leurs cousins plus favorisés ne veulent pratiquement plus en entendre parler. La technologie audiovisuelle est loin de faire l'unanimité chez les professionnels de la muséographie. Quels sont les avantages et les limites de l'audiovisuel au musée? Stagiaire à Museum, Jennifer Schuessler fait le point de la question en s'appuyant notamment sur les recherches faites par le personnel de la rédaction et les stagiaires qui l'ont précédée.
Et qui plus est…
Authors: Šla Tomislav
Published: July 2010

Dans cet article, le muséographe yougoslave bien connu Tomislav Šola, membre du comité consultatif de Museum, présente l'ouvrage Public view: the ICOM handbook of museum public relations (Paris, ICOM, 1986, 1.92 p.).
En toute franchise
Authors: Bruce H. J. , Saks D. Y.
Published: July 2010

Le 3 février 1992, le président de la République sud‐africaine, Frederik De Klerk, et le président du Congrès national africain, Nelson Mandela, assistaient à la cérémonie de remise au président Félix Houphouët‐Boigny du Prix pour la recherche de lapaix créé par l'UNESCO en 1989. Au cours de cette rencontre au Siège de l'UNESCO, à Paris, les deux dirigeants étaient convenus d'unir leurs efforts pour «mettre un terme aux problèmes anciens afin de bâtir l'avenir». Cette volonté de construire une société nouvelle, qui concerne le peuple sud‐africain tout entier, a déjà gagné le monde des musées. H. J. Bruce, conservateur adjoint, et D. Y. Saks, historien, se sont résolument engagés dans la création d'un nouvel Africana Museum. Ils disent leurs efforts pour ouvrir des perspectives nouvelles à l'Afrique du Sud.
Des conférenciers sourds dans les musées de France
Authors: Derycke Béatrice
Published: July 2010

Avec l'appui du musée du Louvre, de la Direction des musées de France, de la Fondation Crédit Lyonnais et de la mairie de Paris, a été créée en juillet 1989 l'association Art visuel international des sourds. Son but: former, en trois ans, des personnes sourdes à l'histoire de l'art. Ainsi le monde des musées s'est‐il ouvert au public privé d'audition. Béatrice Derycke a été l'une des initiatrices de cette entreprise unique au monde.
L'informatisation des collections égyptiennes du Louvre1
Authors: Ziegler Christiane
Published: July 2010

L'informatisation des collections égyptiennes du Louvre a créé un outil de recherche et de savoir unique au monde. Christiane Ziegler est conservateur en chef, chargée du Département des antiquités égyptiennes du Louvre et professeur d'archéologie égyptienne à l'École du Louvre. Elle dirige la mission archéologique à Saqqarah, dans la région du Caire, et elle est membre du Comité international de l'UNESCO pour les nouveaux musées d'Assouan et du Caire.
Le Musée national de Beyrouth ouvre ses portes
Authors: Colin Brigitte
Published: July 2010

La réouverture prochaine de quelques salles du Musée national de Beyrouth après plus de quinze ans de guerre marque une étape importante dans la renaissance de l'identité nationale des Libanais. Brigitte Colin, architecte diplômée de l'École des beaux‐arts de Paris, assure, depuis son entrée à l'UNESCO en 1982, le suivi technique des projets de patrimoine culturel dans la région arabe.
Exposer l'environnement: le musée du High Desert, en Oregon
Authors: Gardner George S.
Published: July 2010

Aux États‐Unis d'Amérique, un musée à la fois classique et de plein air dans un État du Nord‐Ouest est une vitrine spectaculaire où peut se mesurer l'influence des humains sur l'environnement. Le spectacle des animaux dans leur habitat naturel sensibilise le public à la nécessité de conserver et de protéger les énormes ressources de la région. George S. Gardner, consultant, est un spécialiste de l'aménagement des musées, établi à Ossining, dans l'État de New York; pendant plus de vingt ans, il a travaillé pour le Musée américain d'histoire naturelle.