bluuebunny/crossref_metadata_2025 huggingface dataset:
Hippocampal neuronal atrophy occurs in rhesus macaques following infection with simian immunodeficiency virus
Authors: Luthert P. J. , Montgomery M. M. , Dean A. F. , Cook R. W. , Baskerville A. , Lantos P. L.
Published: May 2008

There is strong evidence that patients with AIDS have loss of cortical neurons. In this study we have examined the hippocampus of rhesus monkeys infected with simian immunodeficiency virus (SIV) to determine whether neuronal damage occurs in this model of human AIDS and to investigate its time course. Twenty‐eight infected monkeys (2 3 young [<9 years] and five elderly [>16 years]) were compared with 11 controls (six young and five elderly). Numbers of nucleolated neurons per unit area of section and mean pyramidal cell diameters were measured in each CA sub‐field of each animal. There was neuronal atrophy in all regions examined, as early as 3 months following inoculation. An initial apparent increase in neuronal density at 3 months did not reach statistical significance. In younger animals, however, there was a later, significant association between the reduction in neuronal density and duration of infection. Elderly animals were only examined at a single, early time point. These results show that there is neuronal pathology following infection with SIV and that there is probably subsequent neuronal death.
Patterns of glial cell activity in fronto‐temporal dementia (lobar atrophy)
Authors: Cooper P. N. , Siddons C. A. , Mann D. M. A.
Published: May 2008

Fronto‐temporal dementia is a clinical syndrome with a number of pathological substrates, including frontal lobe degeneration. Pick's disease, and motor neuron disease with dementia; it also includes patients with a primary progressive language disorder. Twenty‐four brains were examined, using immunohistochemistry for glial fibrillary acidic protein (GFAP) and ferritin. Five cases of fronto‐temporal dementia with a Pick's disease type of histology showed marked cortical gliosis with striking microglial activity in both grey and white matter. In seven cases of frontal lobe degeneration, there was little gliosis and microglial activity was confined largely to the white matter; two of the seven cases of progressive language disorder showed similar changes to frontal lobe degeneration. Five cases of motor neuron disease with dementia showed both astrocytic and microglial activity within the white matter. We suggest that cases of fronto‐temporal dementia due to Pick type histology may result from a process which primarily involves grey matter, whereas cases of frontal lobe degeneration might represent a disorder of white matter.
Acquired multifocal myofibrillar disruption selective of type II fibres
Authors: Putzu G. A. , Figarella‐Branger D. , Baeta A. M. , Lepidi H. , Pellissier J‐F.
Published: May 2008

We report three cases of patients who complained of myalgia showing histological features similar to tubular aggregates in their muscle biopsies. All had an elevated erythrocyte sedimentation rate without any evidence of infectious or autoimmune disease. On electron microscopy, small areas of myofibrillar degeneration, selectively in type II fibres, were found in all patients, but no tubular aggregates were seen. Although the pathogenesis of these lesions is unclear, it does seem that this condition is acquired and transient.
Cytoskeletal changes in cultured human fibroblasts following exposure to 2,5‐hexanedione
Authors: Passarin M. G. , Monaco S. , Ferrari S. , Giannini C. , Rizzuto N. , Moretto G.
Published: May 2008

M. G. Passarin, S. Monaco, S. Ferrari, C. Giannini, N. Rizzuto and G. Moretto (1996) Neuropathology and Applied Neurobiology 22, 60‐67

Cytoskeletal changes in cultured human f ibroblasts following exposure to 2,5‐hexanedione

In the present study, the effects of the 2,5‐hexanedione (HD) on the various cytoskeletal components of human eukaryotic cells were investigated. Primary cultures of human fibroblasts from three healthy donors were exposed to 2.8 mM HD for 14 days; unexposed cultures were used as controls. At different time intervals, cells were counted and the growth curves compared. After 14 days of treatment, the cultures were processed for immu‐noblotting, immunocytochemistry and ultrastructural studies. As compared to controls, morphological abnormalities induced by HD consisted of modification of the cell shape, formation of tangles composed by 10 nm filaments and cytoplasmic segregation of microtubules and membrane‐bound organelles. By immunocytochemistry, the tangles of cytoplasmic filaments were stained by an antibody specific for vimentin. By immunoblotting, the anti‐vimentin antibody recognized only bands of 50‐60 kDa. Comparison of growth curves between treated and control fibroblasts clearly revealed an interference of HD with the cell cycle. The present results demonstrate that the cytotoxicity of HD is not restricted to intermediate filaments, but affects other cytoskeletal components, such as microtubules, as suggested by the impairment of cell division cycle
The expression of the endothelial cell antigen CD34 in demyelinating disease
Authors: Allen I. V. , McQuaid S. , McMahon J. , Crangle K. , McConnell R.
Published: May 2008

In this study, the antigenic expression of CD34, a 110 kDa glycoprotein which is expressed on human haemopoletic cells and vascular endothelium, has been assessed in variety of neuropathological conditions, including infectious and demyelinating disease. Using immunop0eroxidase staining on paraffin sections, the immunohistochemical results show that CD34 antigen is expressed widely on human CNS endothelium in grey and white matter, in the eye including retina, and in the anterior and posterior lobes of the pituitary. In demyelinating disease CD34 antigen expression was not detected in old lesions. CD34 endothelial positivity was observed in areas of gliosis, vasogenic oedema, vascular disease and in Alzheimer's and Parkinson's disease pathology. A general pattern emerger, with CD34 antigen reactivity predominantly but positive in adjacent non‐inflamed tissue, irrespective of myelin pathology. We conclude that perivascular inflammation is a key factor in the absence of immunoreactivity of CD34 in the CNS in demyelinating disease.
Telencephalic transplants in mice: characterization of growth and differentiation patterns
Authors: Isenmann S. , Brandner S. , Sure U. , Aguzzi A.
Published: May 2008

Telencepalic grafting represents a powerful tool for developmental studies and for the investigation of biological features of transgenic brain tissue. The interpretation of grafting experiments. however, requires detailed knowledge of graft biology. Therefore, we have characterzed growth rates, graft size, and differentiation of embryonic telecephalic tissue harvested at various developmental stages and grafted into the caudoputament and lateral ventricles of histocompatible mice. A total of 164 grafts were analysed up to 500 days after transplantation. Of all transplants, 79.3% resulted in the formation of solid neural grafts. Grafted cells were identified by ‘H‐thymidine labelling and autoradiography’. Proliferation was studied by bromodeoxyuridine incorporation and decreased from an initial 35% at 1‐3 d after grafting to less than 1.6% after 40 days. The graft size was measured as a function of the embryonic age of the transplanted tissue. Our data indicate that telencephalic tissue harvested at embryonic day E 12.5 reproducibly yields large, fully differentiated neuroectodermal grafts. The parameters defined in this study will be useful for detailed analysis of neuroectodermal tissue from mice undergoing fatal neurodegeneration, such as knockout mice bearing lethal mutations.
Astrocytes in the hypoglossal nuclei of sudden infant death syndrome (SIDS) infants: a quantitative study
Authors: Pamphlett R. , Treloar L.
Published: May 2008

It has been suggested that brain stem hypoxia or ischaemia underlies the sudden infant death syndrome (SIDS), but previous reports of astrocytosis in the brain stems of SIDS infants have been contradictory. A volumetric quantitative technique was, therefore, developed to compare astrocyte numbers and sizes in the hypoglossal nuclei of SIDS and control infancts. In 12 SIDS and eight control infants, serial sagittal sections were taken through the hypoglossal nucleus and every tenth section through the h ypoglossal nucleus and every tenth section was stained for glial fibrillary acidic protein. Astrocytes were counted in the central 4% of a grid stepped throughout the hypoglossal nucleus, and the heights of 100 astrocyte nuclei were measured with a mocrocator. Astrocyte number, corrected for section thickness and nuclear height, was divided by the volume of the hypoglossal nucleus to calculate astrocyte density. Numbers of astrocytes did not differ significantly between SIDS (mean number 44 729, SD 12 096) and control (mean number 46 562, SD 11 060) infants. Astorcyte nuclear height did not differ significantly between groups (SIDS: mean height 3.98μm, SD 0.31). Astrocyte density was similar in SIDS (mean density 24 378 astrocyte/mm3, SD 6155) and control (mean density 23 978 astrocytes/mm3, SD 4031) infants. No quantitative evidence of astrocytosis was found in the hypoglossal nuclei of SIDS infants. This implies that SIDS infants die without previous episodes of hypoxia/ischaemia severe enough to damage the brain stem.
Diagnostic evaluation of the substantia nigra
Authors: McRitchiet D. A. , Halliday G. M. , Pamphlett R.
Published: May 2008

An improved method for the histopathological evaluation of the substantia nigra for diagnostic purposes is proposed. This method takes advantage of the natural architecture of the constituent cell clusters of the substantia nigra by combining standardized sections in the horizontal plane and simple quantification. The use of this standardized technique should increase the diagnostic reliability and sensitivity of patterns of cell loss within the substantia nigra.
The response of the 22A strain of scrapie agent to microwave irradiation compared with boiling
Authors: Taylor D. M. , Diprose M. F.
Published: May 2008

The 22 A strain of scrapie agent was exposed to boiling or microwave irradiation. Subsequent bioassay in IM and VM mice showed that neither treatment had inactivated the agent. Although IM and VM mice are homozygous for the p7 allele of the Sine gene which controls the incubation period of scrapie in mice, the incubation period for unheated 22A was 22 days longer in IM compared with VM mice. This suggests that other unidentified genes can have a more minor effect on incubation period. The difference between the IM and VM incubation period with microwave‐irradiated 22A was much the same as for the unheated control but was increased to 68 days after boiling. The conclusion is that the agent is modified in some way by boiling but not by microwave irradiation such that it is more subject to the influence of genes other than Sine which affect incubation period.
Parvalbumin and calbindin D‐28 k immunoreactivity in dorsal root ganglia in acquired immunodeficiency syndrome
Authors: Nagano I. , Shapshak P. , Yoshioka M. , Xin K. Q. , Nakamura S. , Bradley W. G.
Published: May 2008

Various degrees of neuronal degeneration have been found in lumbosacral dorsal root ganglia of patients with acquired immunodeficiency syndrome (AIDS). To characterize the subpopulations of primary sensory neurons affected in AIDS. we immunostained dorsal root ganglion tissues from 11 AIDS patients and six controls using antibodies to the calcium binding proteins, parvalbumin and calbindin D‐28 k. In controls, the proportion of neurons containing parvalbumin and calbindin was 18.0% and 22.4%, respectively. The majority of parvalbumin‐positive neurons, which are thought to be proprioceptive neurons, were of medium to large size, while calbindin was found in both large‐ and small‐sized neurons. The density of parvalbumin‐immunoreactive neurons was reduced by 7.3% in AIDS patients, but the density of calbindin‐immunoreactive neurons was preserved. Furthermore, in AIDS cases, the number of parvalbumin‐positive neurons was reduced more in dorsal root ganglia in which human immunodeficiency virus (HIV) antigen was detected than in HIV‐negative ganglia. These results suggest that specific subpopulations of sensory neurons positive for parvalbumin may be differentially affected over the course of AIDS, and that this could be related to peripheral neuropathy which frequently occurs in the late stages of AIDS.
Effect of histamine and the H2 antagonist cimetidine on the growth and migration of human neoplastic gila
Authors: Finn P. E. , Purnell P. , Pilkington G. J.
Published: May 2008

Histamine is known to act, at least in part, as a growth factor, as production of this neurotransmitter has been found to accelerate the rate of tissue proliferation in wound repair, embryogenesis and malignant growth. Histamine favours in vivo tumour cell proliferation via H2 receptors. Cimetidine is an H2 blocker and has been shown to inhibit tumour cell growth. In the present study, the growth modulating effects of histamine and cimetidine were assessed on five cell lines derived from human brain tumours of different histological types and grades of malignancy. Each cell line was treated with either cimetidine or histamine for 24 h before kinetic analyses, with PCNA, or motility assays, using Transwell migration chambers incorporating a microporous membrane, were carried out. Cimetidine significantly inhibited cell proliferation in three out of the five cell lines, which may indicate the dependence of proliferation of these cell lines on stimulation of the H2 receptor. With regard to migration, it was observed that in the majority of cell lines, cimetidine induced migration whilst histamine inhibited it. It was concluded that the link between effects of histamine on proliferation and its effects on migration must be clarified using a larger sample of cell lines.
Differentiation of Purkinje cells in cerebellar slice cultures: an immunocytochemical and Golgi EM study
Authors: Tauer U. , Volk B. , Heimrich B.
Published: May 2008

In the rat central nervous system, the cerebellar cortex has a stereotypical cytoarchitecture and a characteristic connectivity pattern, both mainly formed post‐natally. Organotypic cultures of immature cerebellar tissue were used to study the formation of the cerebellar lamination and the differentiation of Purkinje cells in the absence of their extracerebellar afferents. The lamination was retained in the majority of the cerebellar cultures and most Purkinje cells were aligned. Axonal profiles of Purkinje cells, immunolabelled for UCHT1 or anti‐calbindin D‐28 k, followed pathways similar to those in vivo cerebellum. The dendrites were orientated towards the superficial layer except of those neurons which were ectopically positioned. Unlike in vivo, the dendritic arborization of Golgi‐impregnated/gold‐toned or immuno‐stained Purkinje cells was reduced and the dendritic spines were often elongated. Somatic spines, a morphological feature of immature Purkinje cells persisted even after 4 weeks in culture. We conclude that the Purkinje cells in organotypic cultures send their axon to the correct target region independent of their local position. In contrast the dendritic orientation and differentiation is influenced by the cellular environment and by specific synaptic interaction.
Cell death in the normal developing brain, and following ionizing radiation, methyl‐azoxymethanol acetate, and hypoxia‐ischaemia in the rat
Authors: Ferrer I.
Published: May 2008

Naturally occurring (programmed) cell death in the developing brain has morphological characteristics of apoptosis and is associated with internucleosomal DNA fragmentation. Apoptosis also plays a role in cell death following hypoxia‐ischaemia in the developing rat brain. Ionizing radiation‐induced cell death in the brain of the young rat has morphological characteristics of apoptosis. is mediated by protein synthesis and is associated with internucleosomal UNA fragmentation. Methylazoxymethanol (MAM) acetate injection in the young rat produces apoptotic cell death in the external granule cell layer of the cerebellum. In addition, strong c‐Jun immunore‐activity is observed in apoptotic cells during normal development and following experimentally induced cell death. Moreover, c‐Jun mRNA induction and de novo c‐Jun protein synthesis, together with activation of c‐Jun/AP‐1, as revealed with gel mobility shift assay, occurs in irradiated animals. Western blotting of total brain homogenates shows a c‐Jun‐immunoreactive band at p39, which corresponds to the molecular weight of c‐Jun. in control rats. However, a thick c‐Jun‐immunoreactive band at about p62, accompanied by a decrease of the p39 band, occurs in irradiated and MAM‐treated rats. A thin band immediately above the thick p62 band, suggestive of c‐Jun phosphorylation, is also observed in treated rats. Taken together, these observations indicate that c‐Jun expression is associated with apoptotic cell death in the developing central nervous system.
Overexpression of nestin and vimentin in the ependyma of spinal cords from hydrocephalic infants
Authors: Takano T. , Becker L. E.
Published: May 2008

The ependyma of the spinal central canal in cases of hydrocephalus shows abnormalities which vary with the aetiology of ventricular dilatation. To determine whether these ependymal changes are developmental or reactive in nature, immunohistochemical findings were compared between nine normal controls and 12 cases of hydrocephalus (three each of congenital aqueductal stenosis, Dandy‐Walker malformation, Chiari type II malformation, and post‐haemorrhagic hydrocephalus) using antisera to nestin, vimentin and glial fibrillary acidic protein. The main pathological findings were disruption of ependymal layer, apparent pseudostratification of ependyma, expansion, cleft or syrinx formation in relation to the central canal, and ependymal rosette formation. In normal developing fetal spinal cord, nestin and vimentin were expressed mainly in pseudostratified ependymal cells and radial fibres in the median septum. In cases with congenital hydrocephalus (congenital aqueductal stenosis, Dandy‐Walker malformation, and Chiari type II malformation), nestin was overexpressed in immature ependymal cells, and strong vimentin immunoreactivity was detected in the long tract of radial fibres in the median septum. Nestin and vimentin were also expressed in small cells and their fibres which covered areas denuded of ependymal cells in cases of Chiari type II malformation and post‐haemorrhagic hydrocephalus. Two conclusions are suggested by this report. First, the ependyma of the spinal central canal in congenital hydrocephalus shows a delay in maturation of radial glial cells into mature astrocytes and ependymal cells. Second, areas of ependymal denudation may be repaired by the immature glial cells derived from subependymal cells.
Prion protein immunocytochemistry – UK five centre consensus report
Authors: Bell J. E. , Gentleman S. M. , Ironside J. W. , McCardle L. , Lantos P. L. , Doey L. , Lowe J. , Fergusson J. , Luthert P. , McQuaid S. , Allen I. V.
Published: May 2008

Creutzfeldt‐Jakob disease (CJD) and other prion diseases are associated with the deposition of insoluble prion protein (PrPCJD) in the central nervous system (CNS). Antibodies raised against PrPCJD also react with its precursor protein, a soluble form of PrP (PrPC), which is widely distributed in the normal CNS. This cross‐reactivity has in the past raised doubts as to the specificity and diagnostic reliability of PrP immunolocalization, especially in familial cases which are atypical clinically and which lack characteristic pathology findings. Following an MRC‐funded workshop which focused on this problem, a multicentre prospective study was set up to identify a reliable protocol for PrPCJD immunocytochemistry. Five UK centres took part in this study and demonstrated consistent staining of plaques, vacuolar deposits in severe spongiform change, and perineuronal deposits using a variety of antibodies and enhancement procedures. A protocol using formic acid, guanidine thiocyanate, and hydrated autoclaving pre‐treatment in conjunction with a monoclonal PrPCJD antibody produced the clearest immunochemical results and is presented as the consensus UK recommendation for PrPCJD immunocytochemical procedures.
First Alfred Meyer Memorial Lecture. Epileptic brain damage: a consequence and a cause of seizures
Authors: Meldrum B.
Published: May 2008

Alfred Meyer and his colleagues were the first to report (1954–1956) that the most frequent pathology in tissue from patients with complex partial seizures successfully treated by anterior temporal lobectomy is mesial temporal sclerosis, and that the majority of patients with this lesion give a history of a prolonged seizure early in life. These observations have been repeatedly confirmed. Experimental data from animal models strongly supports the hypothesis that a prolonged generalized or limbic seizure in early life damages the hippocampus and other limbic structures, facilitating an epileptogenic process that, after a latent period, gives rise to spontaneous limbic seizures. Some mechanisms potentially contributing to this process have been identified.
DNA fragmentation in normal development of the human central nervous system: a morphological study during corticogenesis
Authors: Simonati A. , Rosso T. , Rizzuto N.
Published: May 2008

Refinement of the cell number by programmed cell death is a major morphogenetic mechanism of the developing central nervous system (CNS) in vertebrates including mammals, which determines to a significant degree its mature cytoarchitecture. We have examined the topography and the extent of cell death in different regions of the human CNS prenatally (11 fetuses), and in the early post‐natal weeks (three newborns). Attention was focused on the wall of the telencephalon during a relatively short time period (12th–23rd week of gestation), corresponding to the time of major proliferation in the ventricular zone and to the peak of neuronal migration; both these mechanisms are crucial for corticogenesis. The TUNEL method was used, allowing the recognition of cell death because of its ability to label blunt ends of double‐stranded DNA breaks. Morphological features of nuclei at different stages of apoptosis were identified, providing better evidence of the extent of the process than histological stains. Cell labelling was seen in either post‐mitotic elements in the ventricular zone, or along the migratory pathways in the intermediate zone and subplate at all prenatal ages examined. No apoptotic nuclei were seen in the cortical plate. These findings suggest that apoptotic cell death drives the selection of cells which are committed to play a role during the early stages of corticogenesis. Lack of evidence of clonally related apoptotic cells also indicates that cell death occurs randomly. Therefore, molecular signals from the surrounding microenvironment seem to be necessary for the apoptotic pathway to be turned on, thus determining the fate of post‐mitotic cells.
Workshop Report
Authors: Ruchoux Marie‐Magdeleine , Goebel Hans H.
Published: May 2008

No Abstract
Meeting Report
Authors: Hainfellner Johannes A. , Budka Herbert
Published: May 2008

No Abstract
Principles and practice of ‘high risk’ brain banking
Authors: Bell J. E. , Ironside J. W.
Published: May 2008

The storage of tissues obtained from patients with clinically documented and neuropathologically validated diseases of the central nervous system (CNS), and from well‐chosen control cases, forms a valuable resource for present and future research needs. In particular, it facilitates immediate application of new investigative technology as this becomes available. To maximize their usefulness it is desirable to store tissues in a variety of different forms, including fixed and frozen samples. However, storage of infective dementias poses special problems (including risk to future users) since the infective agent may well survive long‐term storage at −70°C. Guidelines for optimal storage of such tissues should conform with safety, but should not be so prescriptive as to deter pathologists who do not have access to sophisticated brain banking resources. This article provides information about tissue storage from infective CNS diseases for pathologists who may require to retain frozen and other samples from such autopsies either occasionally or on a regular basis. Guidelines are offered for banking tissues from cases infected with human immunodeficiency virus (HIV), hepatitis viruses and prions, with detailed description of procedures for acquisition, storage and transport of high‐risk samples. Safety issues and protocols for response to accidental injury involving exposure to these agents are highlighted in this article.
Effect of seizures on hippocampal peptidergic neurons
Authors: Mitchell J. , Cook I. , Hervey V.
Published: May 2008

Results from animal studies and from human tissue removed from epileptics show that certain subgroups of hippocampal neurons are more vulnerable to seizure activity than others. It is possible that neurons which contain calcium‐binding proteins, such as parvalbumin, may be protected from the high calcium overload that results from seizure activity. In the present study, seizures were induced by an injection of tetanus toxin into the rat hippocampus. A morphological and quantitative analysis was made of the parvalbumin‐containing neurons and of those which co‐localized somatostatin and neuropeptide Y. At 2 weeks there was a generalized increase in immunoreactivity in both groups of neurons. From 1 month through to 3 months after injection, the up‐regulation in immunoreactivity was sustained in the surviving hilar neurons which co‐localized somatostatin and neuropeptide Y but there was a marked reduction in immunoreactivity of the parvalbumin neurons. Althoughthere was no evidence for a loss of parvalbumin neurons there was a small and significant reduction in the number of somatostatin+neuropeptide Y double‐labelled neurons in the contralateral hilus at 3 and 4 months after a tetanus injection. The vulnerability of the somatostatin+neuropeptide Y double‐labelled hilar neurons but not of the parvalbumin‐containing, presumed, basket cells are considered in terms of their connectivity.
The diagnosis of diffuse axonal injury: implications for forensic practice
Authors: Geddes J. F. , Vowles G. H. , Beer T. W. , Ellison D. W.
Published: May 2008

The diagnosis of diffuse axonal injury (DAI), which may be of considerable importance in forensic medicine, necessitates widespread sampling of the brain for histology. Because a limited sampling method for screening brains for axonal damage would be of value for medico‐legal work, the authors have tested the findings of an earlier study which suggested that a standard set of three blocks from above and below the tentorium could reliably be used in routine practice as a basis for the diagnosis of DAI. A series of 22 previously diagnosed cases of DAI, with a range of survival times, was studied using immunohistochemistry with antibodies to β‐amyloid precursor protein (βAPP), the microglial‐associated antigen CD68 (PG‐M1) and for GFAP. Strict histological criteria were used to assess traumatic damage, and the evolution of the histological changes with increasing survival is described. In four cases, the sampling scheme employed yielded evidence of axonal damage in only one block, and a diagnosis of DAI could have been made in only 13/22 cases. In six of the shortest surviving cases, βAPP positivity in the corpus callosum and brainstem outlined areas of early ischaemia, as well as of traumatic damage, so that interpretation of immunolabelling was not always clear‐cut. The findings suggest that DAI cannot be reliably diagnosed on a restricted number of blocks from vulnerable areas, and that the use of βAPP and PG‐M1 immunocytochemistry may bring interpretative problems that can only be resolved by taking a larger series of tissue samples for histology.
Acrylamide and 2,5‐hexanedione induce collapse of neurofilaments in SH‐SY5Y human neuroblastoma cells to form perikaryal inclusion bodies
Authors: Hartley C.L. , Anderson V.E.R. , Anderson B.H. , Robertson J.
Published: May 2008

C.L. Hartley, V.E.R. Anderson, B.H. Anderson & J. Robertson (1997) Neuropathology and Applied Neurobiology23, 364–372

Acrylamide and 2,5‐hexanedione induce collapse of neurofilaments in SH‐SY5Y human neuroblastoma cells to form perikaryal inclusion bodies

Neurofilament accumulations are characteristic of a number of neurological conditions including amyotrophic lateral sclerosis, giant axonal neuropathies and several chemically‐induced neuropathies. Although the mechanism(s) leading to neurofilament accumulation are unknown, it is possible that similar processes occur both in disease and in chemically‐induced neuropathies. Understanding the mechanism(s) of chemically‐induced neurofilament accumulation, which is more amenable to experimental manipulation, may give insight into the neurological diseases they mimic. We have compared the effects of two chemically‐dissimilar neurotoxins, 2,5‐hexanedione and acrylamide, on neurofilaments in the human neuroblastoma cell line, SH‐SY5Y. Both undifferentiated and differentiated SH‐SY5Y cells were exposed to 2,5‐hexanedione or acrylamide and changes in cytoskeletal organization examined by immunofluorescence and electron microscopy. Although distinct morphological differences have previously been characterized in the neuropathies induced by 2,5‐hexanedione and acrylamide in vivo, we have found that both compounds had similar direct effects on neurofilaments in SH‐SY5Y cells, inducing formation of perikaryal inclusion bodies. In addition, differentiated SH‐SY5Y cells were more sensitive to both 2,5‐hexanedione and acrylamide compared with undifferentiated cells. These similar effects of 2,5‐hexanedione and acrylamide lend further support that a common mechanism(s) may lead to neurofilament accumulation in these neuropathies. SH‐SY5Y cells provide a useful model to investigate further the biochemical basis of neurofilament accumulation.
Effect of changes in the CD44 gene on tumour cell invasion in gliomas
Authors: Bouterfa H. , Janka M. , Meese E. , Kerkau S. , Roosen K. , Tonn J. C.
Published: May 2008

H. Bouterfa, M. Janka, E. Meese, S. Kerkau, K. Roosen & J. C. Tonn (1997) Neuropathology and Applied Neurobiology23, 373–379

Effect of changes in the CD44 gene on tumour cell invasion in gliomas

Cell adhesion is a critical factor in the multistep process of tumour invasion. CD44 is one of the cell surface adhesion molecules responsible for interaction with hyaluronic acid, a component of the CNS extracellular matrix. The aim of the present study was to demonstrate whether alterations in the CD44 gene might account for different invasive behaviour. EcoRI restriction analysis by Southern blot hybridization revealed several additional hybridization signals in tissue specimens of two out of 16 patients with glioblastoma, indicating DNA rearrangements or point mutations, respectively, within the region of the CD44 gene. Expression patterns of CD44 isoforms in these two rearranged gliomas and in 28 other patients with malignant gliomas were analysed by RT‐PCR. All cases displayed only the splice variant CD44H, which acts as hyaluronic acid receptor in glioma tumour cells. Tumour cell invasion was studied with Boyden chamber assays using hyaluronic acid as ligand and functional CD44H blocking antibody. Invasion of cells derived from those gliomas carrying the rearranged CD44 gene locus was decreased by about 50% compared with gliomas without rearrangement, indicating that the altered hybridization patterns in the two glioma samples influenced CD44H mediated glioma cell invasion through hyaluronic acid in vitro. Our results on CD44 isoform expression suggest that, in contrast to other solid tumours, gliomas seem to express only the CD44 variant. Genetic alterations within the CD44 gene might alter the binding domain of the receptor and thus account for different invasive behaviour in glioblastomas.
The abnormal expression of utrophin in Duchenne and Becker muscular dystrophy is age related
Authors: Taylor J. , Muntoni F. , Dubowitz V. , Sewry C. A.
Published: May 2008

J. Taylor, F. Muntoni, V. Dubowitz and C. A. Sewry (1997) Neuropathology and Applied Neurobiology23, 399–405

The abnormal expression of utrophin in Duchenne and Becker muscular dystrophy is age related

Utrophin is a 395 kDa protein with considerable homology to dystrophin. It is highly expressed in the sarcolemma of normal fetal muscle fibres but is confined to neuromuscular and myotendinous junctions, and blood vessels in adult muscle. Sarcolemmal expression occurs on regenerating fibres, irrespective of the disease, and is also seen on mature fibres in Duchenne and Becker muscular dystrophies (DMD, BMD), and inflammatory myopathies. The reasons for the abnormal expression in DMD and BMD are unclear. We have studied this expression of utrophin immunocytochemically on mature fibres in 42 cases of DMD and BMD, aged 3 months–24 years of age. All cases had some mature fibres, with no detectable fetal myosin, that showed sarcolemmal expression of utrophin. The number of these fibres and the intensity of fluorescence was low in young cases before the age of 2 years and increased with age. The fluorescence was graded on a scale of 0 to ++++ and there were significantly more cases under 2 years of age (10/12) with a grading of utrophin of only +, compared with those over 2 years (4/30, P < 0.001). Some revertant fibres, but not all, expressed utrophin and dystrophin. Our data show that the abnormal expression of utrophin on mature muscle fibres in DMD and BMD is not a continuation of the expression that occurs in fetal or regenerating muscle, but is a secondary event caused by unknown factors. The immunocytochemical intensity of utrophin is variable between cases and there is no correlation with clinical severity. As all cases studied had some expression of utrophin on mature fibres, this may be a useful additional tool for distinguishing BMD from other dystrophies, especially in cases with minimal abnormalities in dystrophin expression and/or no detectable mutation in the gene.
Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke
Authors: Anthony D.C. , Ferguson B. , Matyzak M.K. , Miller K.M. , Esiri M.M. , Perry V.H.
Published: May 2008

D.C. Anthony, B. Ferguson, M.K. Matyzak, K.M. Miller, M.M. Esiri and V.H. Perry (1997) Neuropathology and Applied Neurobiology23, 406–415

Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke

Multiple sclerosis (MS) and stroke pathology are characterized by blood–brain barrier breakdown, leucocyte emigration, and tissue destruction. Each process is thought to involve the matrix metalloproteinases (MMP), but little is known of their expression. We undertook to investigate whether MMP expression is dependent on the nature of the CNS lesion and whether expression would coincide with the histopathology. MS or cerebral‐infarct tissue was examined for the presence of gelatinase‐A, gelatinase‐B, matrilysin and stromelysin‐1. Gelatinases A and B and matrilysin expression was found to be up‐regulated in microglia/macrophages within acute MS lesions. In active‐chronic MS lesions, matrilysin and gelatinase‐A expression was pronounced in the active borders. In chronic MS lesions, the expression of matrilysin was confined to macrophages within perivascular cuffs. The pattern of MMP expression in infarct lesions differed considerably. Gelatinase‐B was strongly expressed by neutrophils in tissue from patients up to 1 week after an infarct, whereas gelatinase‐A and matrilysin staining was much less marked. From 1 week to 5 years, neutrophils were absent and the large number of macrophages present were expressing matrilysin and gelatinase A. Only a low level of gelatinase‐A and matrilysin expression was observed in normal brain controls. Thus, MMPs are expressed in inflammatory lesions in the CNS, but their individual expression is dependent on the nature and chronicity of the lesion. However, the general pattern of expression, in perivascular cuffs and in active lesions, supports a role for these enzymes as mediators of blood–brain barrier breakdown and tissue destruction, both in MS and in cerebral ischaemia.
Role of myelin basic protein and proteolipid protein genes in multiple sclerosis: single strand conformation polymorphism analysis of the human sequences
Authors: Price S. E. , Sharpe G. , Boots A. , Poutsma A. , Mason C. , James J. , Hinks L. , Thompson R. J.
Published: May 2008

S. E. Price, G. Sharpe, A. Boots, A. Poutsma, C. Mason, J. James, L. Hinks and R. J. Thompson (1997) Neuropathology and Applied Neurobiology23, 457–467

Role of myelin basic protein and proteolipid protein genes in multiple sclerosis: single strand conformation polymorphism analysis of the human sequences

Susceptibility to multiple sclerosis (MS) is widely held to have a strong genetic component. While the identities of genes conferring susceptibility are currently unknown, possible candidates include those genes coding for proteins which function in central nervous system (CNS) myelin. Two such genes are the human myelin basic protein (MBP) and proteolipid protein (PLP) genes, whose products make up &80% of the total protein in CNS myelin. The association of a variable number tandem repeat (VNTR) 5' to the human MBP gene with MS has been the subject of conflicting reports. Here we test the hypothesis that mutations in the human MBP and PLP genes might be associated with MS by examining the entire expressed sequence of both genes by single strand conformation polymorphism (SSCP) analysis, using a panel of 71 MS patients and 71 controls. We have also re‐examined the VNTR region in patients and controls. Three base changes were found in the human PLP gene and nine base changes in the human MBP gene; these were essentially equally distributed between patients and controls. No preferential distribution of various alleles of the VNTR between patients and controls was found. Although intronic and regulatory regions have not been examined, it would appear unlikely that mutations in these genes coding for the two major CNS myelin proteins contribute significantly to genetic susceptibility to MS.
Proliferation and Dna fragmentation in meningioma subtypes
Authors: Maier H. , Maier H. , Wanschitz J. , Sedivy R. , Rössler K. , Öfner D. , Budka H.
Published: May 2008

H. Maier, J. Wanschitz, R. Sedivy, K. Rössler, D. Öfner and H. Budka (1997) Neuropathology and Applied Neurobiology23, 496–506

Proliferation and DNA fragmentation in meningioma subtypes

Atypical meningioma has been introduced as tumour subtype of intermediate biological behaviour between classical and malignant meningiomas. To substantiate this three‐step scale of malignancy, we assessed the proliferative activity reflected by Ki‐67 (MIB1) labelling index (LI) in a series of 89 meningiomas, including 15 classical, 29 atypical, 35 anaplastic tumours, and 10 haemangiopericytomas and papillary meningiomas. The possible correlation of proliferation with the frequency of apoptosis and their relations to BCL‐2 immunoexpression was investigated in seven classical, 10 atypical and 10 malignant meningiomas. Apoptosis was demonstrated by evaluation of the frequency of apoptotic figures, by the enzymatic technique of in situ tailing (IST) which stains apoptotic DNA fragments, and by DNA preparation and gel electrophoresis demonstrating DNA laddering in frozen tissues of five meningiomas. MIB1 LI revealed a highly significant increase from classical through atypical to anaplastic meningiomas (P 0.0001); haemangiopericytomas and papillary meningiomas were well within the range of atypical meningiomas. IST indices rose with increasing malignancy and correlated with MIB1 LI (P 0.0001); they showed a weak inverse correlation with BCL‐2 immunoexpression (P= 0.05). BCL‐2 expression tended to decrease with malignancy grade and was unrelated to MIB1 LI or frequency of apoptosis. Our data show that (i) apoptosis is a feature of meningiomas, significantly correlated with the malignancy scale, (ii) DNA fragmentation shows significant correlation with proliferation and inversely with BCL‐2 expression; (iii) proliferation indices and frequencies of apoptosis/DNA fragmentation within meningioma subgroups corroborate the intermediate biological position of the atypical meningioma between classical and malignant meningiomas.
Case report
Authors: Dawson T. P.
Published: May 2008

T. P. Dawson (1997) Neuropathology and Applied Neurobiology, 23, 516–520

Pancytopaenia from a disseminated anaplastic oligodendroglioma

The rarity of extraneural metastases from a central nervous system (CNS) tumour may mean that the manifestations of a metastatic lesion are confused with a second pathology. This report concerns a patient who developed a fatal and clinically unexplained, pancytopaenia 3 months after removal of an anaplastic oligodendroglioma. Post‐mortem revealed widespread bone marrow dissemination of the CNS primary and a solitary liver metastasis. A brief review of the literature and some possible reasons for the rarity of extracranial metastases are discussed.
Boosting Anti‐idiotype Immune Response with Recombinant AAV Enhances Tumour Protection Induced by Gene Gun Vaccination
Authors: Cesco‐Gaspere M. , Zentilin L. , Giacca M. , Burrone O.R.
Published: May 2008

Thanks to the safety of administration, efficiency of in vivo transduction and persistence of transgene expression, vectors based on the adeno‐associated virus (AAV) are extensively utilized in both preclinical and clinical experimentation. Here we thoroughly explore the potential of AAV‐mediated antigen delivery for tumour vaccination. A recombinant AAV vector (rAAV) encoding a lymphoma idiotype (Id) in a single‐chain variable fragment format was found to induce an efficient anti‐Id immune response upon injection in immunocompetent animals. The intensity of the immune response and the protective effect of rAAV administration in vivo were systematically compared with those elicited by simple injection of naked DNA or biolistic immunization. The results indicate that Id delivery via rAAV enhances the intensity of immune response compared with injection of naked DNA, while anti‐idiotypic antibodies titres are not considerably increased compared with biolistic vaccination. On the contrary, a prime‐boost vaccination strategy combining biolistic and AAV DNA delivery results in a major increase in anti‐Id antibody response compared with the repetitive biolistic immunization. This increased anti‐Id humoral response strictly correlated with a significant improvement on tumour protection in vivo.
Innovation in mechanical weed control in crop rows
Authors: VAN DER WEIDE R Y , BLEEKER P O , ACHTEN V T J M , LOTZ L A P , FOGELBERG F , MELANDER B
Published: May 2008

Weed control within crop rows is one of the main problems in organic farming. For centuries, different weed removal tools have been used to reduce weeds in the crop rows. Stimulated by the demand from organic farmers, research in several European countries over the last decade has focused on mechanisation using harrowing, torsion finger weeding and weeding with compressed air (Pneumat). Intelligent weeders are now being developed which offer more advanced ways to control weeds, including larger ones and to leave the crop plants unharmed. One of the first commercially available intelligent weeders, the Sarl Radis from France, has a simple crop detection system based on light interception, which guides a hoe in and out of the crop row, around the crop plants. The inclusion of innovative technologies, including advanced sensing and robotics, in combination with new cropping systems, might lead to a breakthrough in physical weed control in row crops leading to significant reductions, or even elimination, of the need for hand weeding.
Weeds as hosts for new crop pests: the case of Protortonia navesi (Hemiptera: Monophlebidae) on cassava in Brazil
Authors: OLIVEIRA C M , FONTES J R A
Published: May 2008

Weeds may serve as reservoirs for new and invasive insect pests. The cassava root scale (Protortonia navesi) is a recent pest in the Brazilian ‘Cerrado’ that causes qualitative and quantitative damage by sucking plant sap. Recently, field surveys revealed that many common weeds in this region act as host for P. navesi in cassava fields. In a discrete survey, 15 weed species were identified that were hosting P. navesi. Among these, 13 species occurred during the cropping season and five were observed 4 months after cassava harvest. Eight months after harvest, only cassava volunteer plants were found to be hosting P. navesi. This survey provided a real example of the problem created when weeds host new crop pests. The management of weeds (including crop volunteers) needs to be considered as part of generalised pest management and pest invasion prevention schemes. Effective weed management can be a means of limiting the survival of new pests and the re‐infestation of susceptible crop species in subsequent years. Simple studies like this point to a practical need to create greater collaborations between pest management researchers working within discrete pest categories.
Histological and immunohistochemical evaluation of basal cell carcinoma following curettage and electrodessication
Authors: Filho Lauro Lourival Lopes , De Oliveira de Avelar Alchorne Alice , Pereira Gerson Cotta , Lopes Lauro Rodolpho Soares , De Carvalho Teresinha Castelo Branco
Published: May 2008

Background  Basal cell carcinoma (BCC) is the most frequent non‐melanoma skin cancer. Curettage and electrosurgery is probably the method most commonly used by dermatologists for the treatment of small and low risk BCCs. However, one is unable to determine the persistence of any residual tumor. This study was carried out in order to demonstrate the presence of such tumoral cells after curettage and electrofulguration.

Methods  20 primary BCC outpatients were studied at the Dermatology Service of Getúlio Vargas Hospital in the city of Teresina – State of Piauí– Brazil, with lesions of up to 1 cm in diameter on the face, and up to 1.5 cm elsewhere, and with no clinical signs of sclerosing and micronodular forms. Patients were anesthetized with 2% lidocaine with vasoconstrion and the lesions were curetted. Electrofulguration was conducted throughout the curetted area and 1 millimeter beyond. After two curettage and electrofulguration cycles, an incision around the resultant ulcer was made 2 mm beyond the visible bloody borders and in the base to the middle of subcutaneous fat. Two straight incisions were also carried out intersecting the lesion center, dividing it into quadrants. Each quadrant was incised and then fixed with 10% formalin. The quadrants and the fragments resulting from the curettage were in paraffin and histopathologically tested through hematoxylin/eosin stains and immunohistochemistry with Ber‐EP4 marker.

Results  There was evidence of persistent BCC in 5 of the 20 sites treated (25%): four (20%) in one quadrant and one (5%) in all four quadrants. 70–100% of tumor cells expressed Ber‐EP4 in all 20 BCCs.

Conclusions  The persistence of tumoral residues after 2 curettage and electrofulguration cycles for basal cell carcinoma was found in 5 sites treated (25%). Despite the small cohort, such findings are very similar to those of other studies that applied curettage and electrocoagulation and indicated the probability of 25% of tumoral persistence.