bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular genetic study showing that the IN/157 ‘oligodendroglioma’ cell line has been contaminated by rhabdomyosarcoma (RD) cells
Authors: VENTER D. J. , STRATTONS M. R. , NOBLE M. D.
Published: May 2008

The IN/157 cell line was originally isolated from a human oligodendroglioma biopsy and has been used in recent years to study aspects of glioma cell biology. We established that IN/157 cells carry a relatively infrequent mutation at position three of codon 61 of the N‐ras gene, suggesting that such a mutation may have contributed towards the genesis of the original tumour. However, the mutation was not detectable within the original paraffin‐embedded glioma biopsy from which the cell line was supposedly derived. We thus considered the possibility that the cells had been contaminated by another cell line and, by means of DNA fingerprinting, have demonstrated that the contaminating cell line is the rhabdomyosarcoma line RD. We feel that this study makes several important points regarding experiments which make use of cell lines. We discuss the possible implications of contamination events with regard to erroneous conclusions about the biology of the cell lines and tumour types from which they supposedly derive. We also suggest ways in which future contamination‐related errors can be minimized.
Acute bilateral ballism in a patient with intravascular dissemination of gastric carcinoma
Authors: LAING R. W. , HOWELL S. J. L.
Published: May 2008

An 84‐year‐old woman presented with an acute onset of violent bilateral ballism‐chorea. She was admitted to the local neurology unit, but no definite diagnosis could be made of the underlying condition, although she did appear to have bronchopneumonia. At autopsy the stomach wall was thickened, and the lesser curve lymph nodes were firm and enlarged. A single nodule was noted in the liver while the lungs appeared consolidated. Histology revealed a moderate‐to‐poorly differentiated gastric adenocarcinoma with extensive intravascular dissemination which included the central nervous system (CNS). Numerous small infarcts related to vessels occluded by tumour were present throughout the brain, and we feel that this was the underlying mechanism for the acute onset of ballism.
Immunocytochemical localization of ubiquitin at human neuromuscular junctions
Authors: SERDAROGLU P. , ASKANAS V. , ENGEL W. K.
Published: May 2008

Using several specific monoclonal and polyclonal antibodies, we found that ubiquitin is highly concentrated in the post‐synaptic domain of human neuromuscular junctions. The distribution and pattern of ubiquitin immunoreactivity is identical to the localization of bound a‐bungarotoxin, suggesting that ubiquitin may be involved in post‐translational modification or turnover of the acetylcholine receptor or other junctional proteins of the muscle fibre.
The number and mean volume of neurons in the cerebral cortex of rats intoxicated with acrylamide
Authors: TANDRUP T. , BRENDGAARD H.
Published: May 2008

Acrylamide was given in an accumulated dose of 500 mg/kg to rats by intraperitoneal injection in two different dosing schedules: 50 mg/kg twice a week for 5 weeks and 33.3 mg/kg twice a week for 7.5 weeks. The effect of acrylamide intoxication on the neurons in the cerebral cortex of the rat was studied using unbiased stereological methods. A reduction of brain weight of 8% was seen in both the intoxicated groups. The volume of neocortex was significantly decreased in the experimental groups, but the density of neurons was increased resulting in an unchanged total number of neurons. The mean volume of neurons in neocortex was significantly decreased in both acrylamide intoxicated groups. There was no difference between the two different intoxication schedules. The possibility that acrylamide causes neuronal death and the effect of eventual differential cellular sensitivity is discussed.
A preliminary investigation of promotion of brain tumours by hexachlorophane in Sprague‐Dawley rats transplacentally exposed to N‐ethylnitrosourea
Authors: PURVES D. , DAYAN A.
Published: May 2008

Two‐stage carcinogenesis (initiation and promotion) has been demonstrated in various mammalian tissues, but there is no conclusive evidence that it occurs in the nervous system. The present work has investigated the possibility that it might occur in the brain of the rat.

Pregnant Sprague‐Dawley rats were given an initiating dose (10 mg/kg intravenously (i.v.)) of N‐ethylnitrosourea (ENU), which resulted in a low but consistent yield of brain tumours in the offspring. The dose was determined in a prior dose‐response investigation. The ‘initiated’ offspring were treated postnatally with the putative promoter, hexachlorophane, and its ability to increase tumour incidence was examined by standardized step sectioning of the brain from rats killed at 6 months.

There was no evidence of promotion of ENU‐induced brain neoplasms by hexachlorophane in the rat. The experimental procedure led to a reproducible incidence of glial tumours in the Ppups.
Comparative immunohistochemical study on the expression of αB crystallin, ubiquitin and stress‐response protein 27 in ballooned neurons in various disorders
Authors: KATO S. , HIRANO A. , UMAHARA T. , KATO M. , HERZ F. , OHAMA E.
Published: May 2008

This Report deals with a comparative study on the expression of αB crystallin, ubiquitin, stress‐response protein 27 (srp 27), srp 72 and phosphorylated neurofilament protein (pNFP) by ballooned neurons in Pick's disease, Creutzfeldt‐Jakob disease (CJD), amyotrophic lateral sclerosis (ALS), leptomeningeal carcinomatosis, anterior spinal artery syndrome and pellagra. Immunohistochemical techniques were used. αB Crystallin was expressed by the majority of ballooned neurons of Pick's disease and CJD, but not by those of the other disorders. Ubiquitin and srp 27 expression was also restricted to abnormal neurons of Pick's disease and CJD, but the proportion of stained cells was less than that expressing aB‐crystallin. There was no evidence of ballooned neurons expressing srp 72. Except for those of pellagra patients, phosphorylated neurofilament protein (pNFP) was detected in most abnormal neurons. Our results suggest that the mechanisms involved in formation and maintenance of swollen neurons in Pick's disease and CJD may be different than those of ballooned neurons in the other entities studied.
Ectopic intrapelvic medulloepithelioma: case Report
Authors: FIGARELLA‐BRANGER D. , GAMBARELLI D. , PEREZ‐CASTILLO M. , GENTET J. C. , GRISOLI F. , PELLISSIER J. F.
Published: May 2008

A primary extraspinal medulloepithelioma with lung metastases is Reported. The tumour was located in the presacral area. Microscopically, it showed typical features of medulloepithelioma with focal ependymal differentiation. Medulloepitheliomas are maligant tumours of primitive neuro‐epithelium usually involving the cerebral hemispheres. This Report demonstrates their possible extraspinal presacral occurrence. By immunohistochemistry, neuron‐specific‐enolase, S100 protein, vimentin, cytokeratin and glial fibrillary acidic protein were found in some tumour cells. Electron microscopy demonstrated poorly differentiated cells forming stratified epithelium resting on a basal lamina and short functional complexes at the apical pole. Ultra‐structural evidence of ependymal differentiation was observed. Presario medulloepithelioma may arise from undifferentiated embryonic cells forming the Presario remnants of the neurenteric canal.
Major histocompatibility complex (MHC) antigen expression in HIV encephalitis
Authors: KENNEDY P. G. E. , GAIRNS J.
Published: May 2008

In order to study possible immunopathogenic mechanisms in Human Immunodeficiency Virus (HIV) encephalitis, immunocytochemical localization of Class I and Class II major histocompatibility complex (MHC) antigens was studied in formalin‐fixed tissue sections from the brains of 10 individuals who had died with this disorder. Using the avidin biotin peroxidase technique and monoclonal antibodies to these antigens, increased expression of Class I antigens was found in five out of 10 and of Class II antigens in six out of 10 cases of HIV encephalitis. This contrasted with results obtained with the HIV‐specific anti‐P24 antibody which reacted with only a small number of cells in four cases. Class I and II antigens were detected mainly in perivascular monocytes/macrophages and also in multinucleated giant cells. In two cases, slight labelling was also detected in these cells more diffusely in the brain parenchyma. Immune and viral antigens were not detected in gill cells or neurons. Neither normal control cases nor brain sections from patients who had died from other neurological diseases were labelled with any of the antibodies apart from two cases of varicella‐zoster virus‐associated encephalitis in which increased expression of Class II antigens occurred. These findings support the notion that indirect immune‐mediated mechanisms may be important in the pathogenesis of HIV encephalitis.
Allocortical involvement in Huntington's disease
Authors: BRAAK H. , BRAAK E.
Published: May 2008

Seven brains of individuals who had suffered from Huntington's disease and seven control brains were examined. Preparations stained for Nissl material and lipofuscin pigment revealed a characteristic layer‐specific loss of nerve cells in two allocortical areas, the entorhinal region and the subiculum. The most severe changes occurred in the entorhinal layer Pri‐y while layer Pre‐a, layer Pre‐y and the subiculum showed less severe alterations.
An immunohistochemical study of mononuclear cells in meningiomas
Authors: BØ L. , MØRK S. J. , NYLAND H.
Published: May 2008

A consecutive series of 34 meningiomas were re‐examined as to subtype and presence of nuclear atypia, mitotic figures, areas of high cellularity and necrosis. Meningioma cells were epithelial membrane antigen (EMA) positive in 31 out of the 34 tumours. The presence of mononuclear cells and macrophages was assessed by immunohistochemistry using the monoclonal antibodies L26 (CD20, B cell marker), DF‐T1 (CD43, T cell marker), KPl (CD68, macrophage marker) and MAC387 (monocytes). L26 positive B cells were observed infrequently. CD43 positive mononuclear cells were infiltrating the parenchyma as individual cells and as groups of cells in 29 (87% of the tumours). CD68 positive macrophages were seen in 19 (59% of the tumours), as scattered single cells or groups of cells. There was a statistically significant association between the number of CD68 positive cells (necrotic areas excluded) and microscopic features of aggressiveness, i.e. high cellularity as well as the combination of nuclear atypia and frequent mitotic figures. MAC387 stained only a few cells; the immunopositive cells were present mainly within and around vessels. Meningioma cells displayed a diffuse immunopositivity for L26 (CD20) in 29 out of 34 meningiomas, but did not stain with macrophage markers. Mast cells were found in 9 out of 32 tumours; when present they were significantly more prevalent in the syncytial subtype. Thus, mononuclear cell infiltrates in meningiomas are mainly composed of T cells and macrophages, indicating an immune system surveillance and response to the tumour cells. The functional and prognostic significance of the presence of CD68 positive cells, macrophages, deserve further study in the search for more reliable histological criteria to predict recurrence and biological aggressiveness in meningiomas.
Methyl bromide intoxication and acute energy deprivation syndromes
Authors: CAVANAGH J. B.
Published: May 2008

The case Reported in this issue of symmetrical brain stem damage associated with exposure to methylbromide has affinities with a number of analogous syndromes associated with tissue energy deprivation. Attention is drawn to topographical and metabolic similarities and differences in these conditions, and suggestions are made for possible ways of mitigating the damage in future cases that may also be of value in Wernicke and Leigh's diseases.
Case Report: neuropathology of methyl bromide intoxication
Authors: SQUIER M. V. , THOMPSON J. , RAJGOPALAN B.
Published: May 2008

The neuropathological findings in a man and his dog both of whom died after acute exposure to methyl bromide are presented. The dog had cerebral oedema, most marked in the depths of cortical sulci. The man survived 30 days after the initial illness and his brain contained well‐defined symmetrical lesions in the mammillary bodies and inferior colliculi. He also had a peripheral neuropathy and lymphocytic thyroiditis. The pathology in the central nervous system has features resembling Wernicke's encephalopathology; the mechanism by which methyl bromide may produce such lesions is discussed.
Heat shock protein (hsx70) mRNA expression in human brain: effects of neurodegenerative disease and agonal state
Authors: Harrison P. J. , Procter A. W. , Exworthy T. , Roberts G. W. , Najlerahim A. , Barton A. J. L. , Pearson R. C. A.
Published: May 2008

Heat shock proteins (hsps) are involved in the response by cells to stress including hyperthermia, hypoxia and injury. Previous work has demonstrated expression of messenger RNA (mRNA) encoding 70 kDa hsps (hsp70) in animal brain in response to stimuli such as these. We have used in situ hybridization histochemistry to assess the distribution and quantity of a specific hsp70 (called hsx70) mRNA in frontal cortex and cerebellum from normal and demented patients whose pre‐mortem course had been documented. In cortex, hsx70 mRNA was concentrated over pia mater and glia but was also present over neurons; in cerebellum, hsx70 mRNA was prominent over granule cells but absent from Purkinje cells. Detection of hsx70 mRNA did not correlate with pre‐mortem factors such as pyrexia or coma. Increased hsx70 mRNA was found in frontal cortex white matter in Alzheimer's disease and in a mixed group of other neurodegenerative disorders. No changes occurred in cerebellum. The data provide further evidence for altered hsp gene expression in dementia, and support the existence of a stress response occurring in brains affected by such diseases.
Immunoelectronmicroscopical demonstration of major histocompatibility class II antigen: expression on endothelial and perivascular cells but not Schwann cells in human neuropathy
Authors: Atkinson P. F. , Perry M. E. , Hall S. M. , Hughes R. A. C.
Published: May 2008

A pre‐embedding technique for identifying major histocompatibility (MHC) class II antigen with monoclonal antibody LN3 at the electron microscope level by immunogold silver enhancement was applied to sections from 12 human nerve biopsies. Many perivascular mononuclear cells in the epineurium, perineurium and endoneurium expressed MHC class II antigen and had the morphological appearance of macrophages. Cell processes expressing MHC class II antigen extended throughout the endoneurium, often close to Schwann cells. No MHC class II expression was identified on myelinating or non‐myelinating Schwann cells. The endothelial cells of epineurial blood vessels expressed MHC class II antigen on their luminal surfaces more often and more strongly than those of the endoneurial vessels. These observations indicate that perivascular cells in both the endoneurium and perineurium commonly express the molecules necessary to present antigen to CD4+ T lymphocytes, but Schwann cells do not.
Blood‐nerve barrier: ultrastructural and endothelial surface charge alterations following nerve crush
Authors: Bush M. S. , Reid A. R. , Allt G.
Published: May 2008

Nerve crush results in an enhanced vascular permeability of the endoneurial vessels distal to the lesion. Vascular permeability at the blood‐nerve barrier (BNB) to serum proteins is influenced by many factors, including anionic surface charge, endothelial vesicular transcytosis and the presence or absence of fenestrated vessels. Using mice and rats, the present ultrastructural investigation examined the effect of nerve crush (axonotmesis) on: (1) the distribution of endothelial anionic sites and (2) the appearance of fenestrations in endoneurial vessels after 4 and 14 day intervals as demonstrated with cationic probes. Transient anionic fenestrations developed in a minority of mouse endoneurial vessels in 4‐day crushed nerves, but were not found in 14‐day crushed nerves of mice nor in crushed nerves of rats. The known increase in the permeability of endoneurial vessels in rats and mice was not associated with reduced luminal labelling with cationic ferritin at physiological pH. At pH 2.0 the labelling of glycocalyx moieties (such as sialic acid) with cationic colloidal gold was disrupted in some epi‐and endoneurial vessels of 4‐day rats, but in a greater proportion after 14 days. The enhanced permeability of the BNB during degeneration and regeneration is related to the formation of anionic fenestrations in endoneurial vessels of mice and to the reduced and uneven distribution of endothelial glycocalyx moieties that are anionic at pH 2.0 in rats.
Adaptation of tibial nerve myelinated fibre parameters to reduced limb length caused by irradiation
Authors: Jacobs J. M. , Myers R.
Published: May 2008

Irradiation of a rat hind limb at 15 days of age caused marked shortening of the limb, with a consequent reduction in nerve length. The tibial nerves of the irradiated limbs were examined qualitatively and quantitatively, and compared with the unirradiated nerve. There was no evidence of fibre degeneration and only very occasional myelin abnormalities. Myelinated fibre numbers were very slightly reduced, possibly due to irradiation effects on small myelinated fibres. Internodal lengths were reduced in proportion to limb length. Mean axon diameters were slightly increased, and myelin sheath thickness reduced. This experimental model provides a new method of altering nerve fibre parameters without surgical intervention.
3‐Acetylpyridine‐induced degeneration in the dorsal root ganglia: involvement of small diameter neurons and influence of axotomy
Authors: Beiswanger C. M. , Roscoe‐Graessle T. L. , Zerbe N. , Reuhl K. R. , Lowndes H. E.
Published: May 2008

3‐Acetylpyridine (3‐AP), an analogue of nicotinamide, produces highly selective CNS lesions, the severity of which may be influenced by prior alterations in the metabolic activity of the affected neurons. The present study was undertaken to determine whether prior axotomy modified the response of dorsal root ganglia (DRG) and anterior horn (AH) neurons to 3‐AP. A single administration (50 or 80 mg/kg i.p.) of 3‐AP to adult rats resulted in degeneration of primarily small‐dark DRG neurons by 24 h. The AH neurons were not affected by either dose of 3‐AP. Light and electron microscopy of the DRG revealed a spectrum of damage ranging from loss of Nissl substance and cytoplasmic degradation to frank necrosis with neuronophagia. Frequently, injured neurons exhibited perinuclear aggregation of cytoplasmic organelles with dissolution of Nissl substance, clearing of the peripheral cytoplasm, and formation of large peripheral vacuoles. Occasionally, a second pattern of 3‐AP injury was observed in which the nuclear chromatin of the neurons was condensed and there was formation of small vacuoles throughout the cytoplasm without peripheral clearing or perinuclear aggregation of cytoplasmic organelles. Axotomy induced typical axon reactions in both large‐pale and small‐dark DRG neurons. The combination of axotomy followed by 3‐AP 4 days later produced morphological features characteristic of both axotomy and 3‐AP exposure, but did not appear to alter the incidence of neuronal cell death. The almost exclusive vulnerability of the small dorsal root ganglion neurons to 3‐AP neurotoxicity make this model potentially useful for the study of small fibre neuropathies.
Heterogeneity of centronuclear myopathy shown by flow cytometry of nuclear DNA
Authors: Metze K. , Schnabel R. , Mellin W. , Gullotta F. , Hiddemann W.
Published: May 2008

Determination of nuclear DNA by flow cytometry of skeletal muscle biopsies of three unrelated male patients with centronuclear (myotubular) myopathy demonstrated, in two patients, a normal pattern and, in one case, a near haploid DNA content in c. 60% of all nuclei, indicating muscle tissue mosaicism.
Development of the cortical dysplasia of type II lissencephaly
Authors: Squier M. V.
Published: May 2008

A detailed neuropathological study of five immature brains with type II lissencephaly is reported. The cases described include two pairs of siblings. One infant survived for 2 months after birth, the others died at 18, 20, 20 and 32 weeks of gestation. This series of cases demonstrates the sequence in which the malformation develops from mid‐gestation to post‐natal life and shows that type II lissencephaly is not an intracortical malformation but is the result of massive glial and neuronal ectopia in the leptomeninges. This results from a failure of arrest of neuronal migration due to defects in the integrity of the pial/glial barrier.
Axonal neurofilamentous accumulations: a comparison between human and canine giant axonal neuropathy and 2,5‐HD neuropathy
Authors: King R. H. M. , Sarsilmaz M. , Thomas P. K. , Jacobs J. M. , Muddle J. R. , Duncan I. D.
Published: May 2008

The neuropathy produced by the hexacarbon 2,5‐hexanedione (2,5‐HD) resembles human and canine inherited giant axonal neuropathy (GAN) in the presence of giant axonal swellings that contain accumulations of neurofilaments. The accumulations are both paranodal and internodal in GAN and 2,5‐HD induced neuropathy. Detailed morphometry on the neurofilaments reveals that the changes in human and canine GAN are closely similar and differ from those of 2,5‐HD neuropathy, suggesting that the mechanisms underlying the formation of the axonal neurofilamentous accumulations differ between the two conditions. In both human and canine GAN, the neurofilaments are more closely spaced and are of greater diameter than in 2,5‐HD neuropathy. The changes in the NF in GAN may be the consequence of flattening of the side‐arms of the neurofilaments against the axis of the filaments
Virulent and avirulent strains of Semliki Forest virus show similar cell tropism for the murine central nervous system but differ in the severity and rate of induction of cytolytic damage
Authors: Balluz I. M. , Glasgow G. M. , Killen H. M. , Mabruk M. J. M. E. F. , Sheahan B. J. , Atkins G. J.
Published: May 2008

The pathogenicity of the avirulent, demyelinating A7 strain of Semliki Forest virus (SFV) and the virulent SFV4 strain (derived from an infectious clone) for the central nervous system of adult BALB/c mice following intranasal infection was compared. The techniques used included immunocytochemistry using anti‐SFV antibody and antibodies to cell markers, in situ hybridization (ISH) using a biotinylated cDNA probe specific for SFV, and immunocytochemistry/ISH double labelling. Whereas SFV4 was lethal at 4 days post‐infection, A7‐infected mice appeared normal at all times. Neuronal necrosis in the pyriform cortex was present in both infections, but developed sooner and was more severe iollowing miection with SFV4 than with A7. Intact neurons and putative oligodendrocytes contained viral RNA and virus‐specific antigen in SFV4 infected mice; viral RNA but not virus‐specific antigen was detected in similar cells in A7‐infected mice. These results confirm that SFV4 and A7 share similar cell tropisms for the murine central nervous system, but differ in the severity and rate of development of cytolytic damage. Intranasal infection is an efficient monitoring system for studies of the molecular basis of pathogenicity of SFV infection in mice.
Differential pattern of β‐amyloid protein deposition within cortical sulci and gyri in Alzheimer's disease
Authors: Clinton J. , Roberts G. W. , Gentleman S. M. , Royston M. C.
Published: May 2008

We have quantified the pattern of β‐amyloid protein (βAP) deposition in the sulci and gyri of the frontal cortex in Alzheimer's disease. The distribution pattern in the frontal cortex gyri is unequivocally different from the pattern found in the frontal sulci. These findings, in conjunction with our previous studies, reflect a differential vulnerability between the sulci and the gyri with respect to Alzheimer's disease pathology, sulci being affected to a greater extent. It is probable that the different patterns of deposition relate to the underlying cytoarchitecture of the cortex.
Cytoplasmic expression of the leu‐4 (CD3) antigen in developing Purkinje cells in the rat cerebellum
Authors: Gerloff C. , Knoth R. , Volk B.
Published: May 2008

Although commonly known to represent a T cell receptor (CD3) associated polypeptide, the leu‐4 (CD3) antigen occurs in cerebellar Purkinje cells (PCs) of many species. The monoclonal pan T lymphocyte marker anti‐leu‐4 (CD3) recognizes both the lymphocytic and the Purkinje cell type of this antigen [22]. To obtain more information about the merit of anti‐leu‐4 (CD3) as an investigational tool, we evaluated the expression of leu‐4 (CD3) in PCs of the developing rat cerebellum (in situ) by light microscopy. Positive anti‐leu‐4 (CD3) immunoreaction of PCs did not occur prior to post‐natal day (D) 4. The analysis of immunostaining during cell differentiation revealed three major phases of post‐natal PC maturation including antigenie development of cell somata (phase 1: until D6), dendrites (phase 2: D7‐D11), and axons (phase 3: D12‐D14). A massive post‐weaning expansion of the dendritic arborization led then to the mature PC architecture. Additionally, the leu‐4 (CD3) antigen was observed in ectopic PC dendrites (D10) and in ectopic (mature) PCs. Throughout post‐natal development as well as in mature PCs, the leu‐4 (CD3) antigen was found to be Cytoplasmic. Due to its labile nature, neither an ultrastructural localization nor molecular characterization could be achieved. For the same reason, its application is basically restricted to cryo‐fixed cerebellar tissue. However, at the level of light microscopy, the monoclonal human T cell marker anti‐leu‐4 (CD3) proved to be a useful tool for specific and sensitive labelling of differentiated cerebellar PCs in the rat.
Alzheimer's lesions labelled by anti‐ubiquitin antibodies: comparison with other staining techniques. A study of 15 cases with graded intellectual status in ageing and Alzheimer's disease
Authors: He Y. , Duyckaerts C. , Delaère P. , Piette F. , Hauw J‐J.
Published: May 2008

We compared the densities of lesions immunolabelled with ubiquitin, tau and βA4 antibodies and stained by various silver impregnations, with the intellectual status. The densities of senile plaques and neurofibrillary tangles labelled by anti‐ubiquitin antibody were correlated with the Blessed test score. Ubiquitin‐positive neurofibrillary tangles were less numerous than those labelled by Gallyas, anti‐tau, Bodian's and Bielschowsky's methods. There were five times more βA4 deposits than ubiquitin positive plaques. βA4 deposits could be numerous in cases in which ubiquitin immunolabelling was entirely negative. Bielschowsky's method, silver methenamine and thioflavin S revealed more senile plaques than anti‐ubiquitin, whereas anti‐tau, Gallyas, Bodian's and Cross' techniques revealed similar numbers. Anti‐ubiquitin positive lesions were correlated with the severity of dementia. Compared with other staining methods, sensitivity of anti‐ubiquitin was weaker for neurofibrillary tangles than for senile plaques. These findings suggest that ubiquitin epitopes are linked to the neurofibrillary changes (in the perikaryon or within the senile plaques), and are absent from βA4 deposits, either diffuse or compact.
Neuronophagia in the motor cortex in amyotrophic lateral sclerosis
Authors: Troost D. , Claessen N. , van den Oord J. J. , Swaab D. F. , de Jong J. M. B. V.
Published: May 2008

This study was designed to identify which phagocytic cells in the cerebral cortex of amyotrophic lateral sclerosis (ALS) patients are involved in the process of neurono‐phagia. For this purpose a number of single and double immunocytochemical stains were carried out on five ALS cases which were selected on the basis of the presence of degenerative and phagocytic phenomena in the cerebral cortex. The cortical degenerative process is mainly present in the third and fifth layers and is not restricted to the fifth layer which contains the cell bodies of the Betz cells. The present study indicates that a number of cells are involved in the process of phagocytosis in ALS. Resident macro‐phages (from microglial or perivascular origin) and astrocytes seem to play an immunologically‐mediated role in the disappearance of neurons. Some of the cells involved in the degenerative process, i.e. rounded macrophages and microglia, expressed major histocompatibility class II antigen. The phagocytic cells in neuronophagia were phenotypically identical to perivascular macrophages and not to microglia. Therefore, the process of phagocytosis of neurons appears to be primarily the task of the perivascularly located macrophage.
Neurological reactions in HIV‐infected patients treated with trichosanthin
Authors: Garcia P. A. , Bredesen D. E. , Vinters H. V. , von Einsiedel R. Graefin , Williams R. L. , Kahn J. O. , Byers V. S. , Levin A. S. , Waites L. A. , Messing R. O.
Published: May 2008

Trichosanthin is a ribosome‐inactivating protein that is being studied as a possible treatment for patients infected with human immunodeficiency virus (HIV). We report the clinical and pathological features in two patients who experienced neurological reactions to trichosanthin. Both patients were neurologically asymptomatic prior to treatment but developed coma and multifocal neurological deficits after treatment. Neuropathological examination revealed regions of severe, multifocal necrosis with histiocytic infiltrates. These reactions to trichosanthin may be mediated by soluble factors released by HIV‐infected macrophages.
Anti‐vimentin staining in muscle pathology
Authors: Bornemann A. , Schmalbruch H.
Published: May 2008

The intermediate filaments of immature muscle fibres contain desmin and vimentin; vimentin is lacking in mature fibres. Regenerating fibres react with anti‐vimentin antibodies and more intensely for desmin than mature fibres. The aim of the present study was to evaluate anti‐vimentin staining for muscle pathology. Anti‐vimentin‐reactive fibres were found in 40 of 89 biopsies assessed. Fifteen patients with progressive destructive myopathy, infantile spinal muscular atrophy, clinically suspected Leigh's disease or unclassifiable congenital myopathy had between 1% and 95% vimentin‐positive fibres. Less than 1% positive fibres were found in 25 patients with neuropathy with secondary myopathy or chronic myopathic conditions. Vimentin‐positive fibres were lacking in 20 normal biopsies, in eight biopsies with neuropathic and in 21 biopsies with mild or non‐destructive myopathic changes. We conclude that staining with anti‐vimentin antibodies is a useful indicator for muscle fibre regeneration; it may help establish the diagnosis in infantile spinal muscular atrophy when the histopathology is non‐characteristic. The high incidence of reactive fibres in some congenital or early‐onset disorders may indicate developmental arrest.
CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance
Authors: Kida S. , Pantazis A. , Weller R. O.
Published: May 2008

Cerebrospinal fluid (CSF) drainage pathways from the rat brain were investigated by the injection of 50 μl Indian ink into the cisterna magna. The distribution of the ink, as it escaped from the cranial CSF space, was documented in 2 mm thick slices of brain and skull cleared in cedar wood oil and in decalcified paraffin sections. Following injection of the ink, deep cervical lymph nodes were selectively blackened within 30 min and lumbar para‐aortic nodes within 6 h. Within the cranial cavity, carbon particles accumulated in the basal cisterns but were also distributed in the paravascular spaces around the middle cerebral arteries and the nasal‐olfactory artery. Carbon particles in the subarachnoid space beneath the olfactory bulbs drained directly into discrete channels which passed through the cribriform plate and into lymphatics in the nasal submucosa. Although ink was distributed along the subarachnoid space of the optic nerves and entered the cochlea, the nasal route was the only direct connection between cranial CSF and lymphatics. Arachnoid villi associated with superior and inferior sagittal sinuses were identified and a minor amount of drainage of ink into dural lymphatics was also observed. This study demonstrates the direct drainage of cerebrospinal fluid through the cribriform plate in anatomically defined channels which connect with the nasal lymphatics. Such a pathway is compatible with the observed rapidity of the bulk flow drainage of CSF in the rat, accords with the known specificity of immunological reactions to antigens injected into brain tissue, and may also serve as a route for drainage for lymphocytes and macrophages from the brain to the regional cervical lymph nodes.
A Golgi study of human locus coeruleus in normal brains and in Parkinson's disease
Authors: Patt S. , Gerhard L.
Published: May 2008

The locus coeruleus (LC) of eight adults without neurodegenerative disease and eight patients with Parkinson's disease was investigated by means of the Golgi‐Braitenberg method for formalin‐fixed human autopsy material. As with Golgi studies in the rat and cat, two main neuronal classes could be demonstrated in the human LC: (i) medium‐sized fusiform and multipolar LC neurons known to contain neuromelanin and (ii) smaller neurons of widely varying somatic shape and dendritic arborization which are considered to be intermingled neurons of adjacent brain stem nuclei not containing neuromelanin.

In Parkinson's disease, the Golgi‐impregnated medium‐sized LC neurons were reduced in number. They showed marked reduction of dendritic length, severe loss of spines, dendritic varicosities and swollen perikarya. The last two findings could be due in part to Lewy‐body inclusions. The smaller non‐noradrenergic neurons did not show severe pathological changes by the Golgi impregnation technique, which is in line with the fact that only neuromelanin‐containing LC neurons are affected in the pathological process of Parkinson's disease.
Characterization of the microglial response in murine scrapie
Authors: Williams A. E. , Lawson L. J. , Perry V. H. , Fraser H.
Published: May 2008

The nature of the glial and inflammatory cell responses to infection in scrapie–affected brains was studied in terminally–affected mice of Ave scrapie models. There were marked astrocytic and microglial responses. Microglia showed increased staining of the surface antigens F4/80, leucocyte–common antigen, type 3 complement receptor, and elevated endocytotic and lysosomal activity. In all models, the astrocytic and microglial responses were largely restricted to anatomical regions of the brain showing vacuolation and/or plaque formation and pathological accumulations of PrP. Expression of MHC Class II was patchy and present on microglia in the neuropil of areas with the most intense microglial activation and on occasional perivascular macrophages. This microglial response may represent a modified form of inflammatory response.
Oligodendrocyte reactions and cell proliferation markers in human demyelinating diseases
Authors: Morris C. S. , Esiri M. M. , Sprinkle T. J. , Gregson N.
Published: May 2008

We have carried out immunocytochemical reactions using antibodies to markers of oligodendrocytes, astrocytes, microglia and proliferating cells (PCNA) in sections of human brain in a variety of demyelinating conditions and human immunodeficiency virus (HIV) infection. In the acute phases of demyelinating diseases we found marked reactive changes in oligodendrocytes with hyperplasia and an increased cytoplasmic reaction using antibodies to enzymes involved in myelin formation. Proliferative responses were implied by the hyperplasia and the common finding of clusters of two or three adjacent oligodendrocytes at sites of acute myelin dam age. This was borne out by studies using the PCNA antibody which gave negative reactions in normal brain but positive reactions in acute demyelination. Double staining for PCNA and cell markers showed that cells that had entered the cell proliferation cycle were to be found among astrocytes, microglia/macrophages and oligodendrocytes. In chronic demyelinating conditions, numbers of oligodendrocytes were reduced and cells in the proliferative cycle were not present, suggesting that the reactive potential of oligodendrocytes or their precursors and their capacity to respond to demyelination is limited.
Defining the limits of prion disease
Authors: Ridley R. M.
Published: May 2008

The term prion disease applies to any disease in which there is an accumulation in brain of the abnormal isoform of prion protein, known as PrPsc. These diseases include all the transmissible spongiform encephalopathies of humans and animals and their related atypical forms. Although there are clear clinical and neuropathological indicators in the majority of cases, the atypical forms present particular diagnostic difficulties because their clinical presentation may closely resemble much more common forms of dementia. On pathological examination the brain may show no spongiform encephalopathy, and attempts at transmission are often not successful in these cases. There are various biochemical and immunohistochemical ways in which prion disease can be detected. Some of these require the use of fresh/frozen tissue which is often not available unless prion disease is already suspected. Some previously unsuspected cases have been detected by genetic analysis of the PrP gene. This approach must be used with caution since there are several rare polymorphisms in the PrP gene which are not pathogenic and possession of a pathogenic mutation does not prevent the occurrence of more common neurological disorders at an earlier age, some of which may be treatable.
The molecular genetics of schizophrenia
Authors: Cardno A. G. , McGuffin P.
Published: May 2008

There is strong evidence for a genetic component in schizophrenia but its precise nature remains unclear. Positional cloning and studies of potential candidate genes offer prospects for progress. The diagnosis of schizophrenia can now be made reliably but questions remain over the most valid phenotypic definition. To deal with this and uncertainties regarding mode of transmission a ‘polydiagnostic’ approach is advisable. A wealth of new DNA markers has enhanced the potential for linkage studies which have so far focused on large multiply–affected families. Multi–centre collaborative studies that are currently under way are likely to identify genes of major effect but other strategies are required if it turns out that most cases result from the combined effect of multiple genes.
A molecular and cellular model to explain the differences in reactivation from latency by herpes simplex and varicella–zoster viruses
Authors: Kennedy P. G. E. , Steiner I.
Published: May 2008

There are marked similarities in the biological properties of the human neurotropic herpesviruses herpes simplex virus type 1 (HSV–1) and varicella–zoster virus (VZV), including their ability to establish lifelong latent infections in human peripheral sensory ganglia (PSG). Despite this, their patterns of reactivation are quite different: HSV–1 reactivations occur many times during a lifetime, they are localized to the cutaneous distribution of a single sensory nerve, they are not associated with sensory symptomatology and their frequency decreases with age. VZV recurrence on the other hand is usually a single event which tends to appear with advancing age, its cutaneous eruption involves an entire dermatome and is usually extremely painful. To help explain these differences, we have formulated a model based on current knowledge of the molecular and cellular basis of latent infection in the nervous system. We suggest that the amount of latent viral DNA and RNA in the latently infected tissue (higher with HSV–1), the cellular location of latent virus (neuronal in HSV–1, probably non–neuronal in VZV), the presence or absence of viral replication in the PSG during reactivation together with the host immune response, are all key determinants of the clinical expression of viral reactivation.
Neuroendocrine–immune interactions in homeostasis and autoimmunity
Authors: Smith T. , Cuzner M. L.
Published: May 2008

Recent experimental evidence confirms the interrelationships between the central nervous, neuroendocrine and immune systems. Indeed, extensive duality exists in the use of neurotransmitters, hormones and receptors each system displays. In the present annotation, the effect of cytokines, soluble mediators of immune function, on the CNS and neuroendocrine systems is addressed and conversely, we discuss the modification of the immune compartment by the sympathetic nervous and neuroendocrine systems, with particular reference to the role of noradrenaline and corticosterone. Dysfunction between the systems is considered in the context of autoimmune conditions, with emphasis on experimental allergic encephalomyelitis and the contribution of corticosterone–driven T–cell apoptosis to recovery from the disease. Finally, we speculate on the relevance of neuroimmune interactions in the pathogenesis of multiple sclerosis.
Hierarchical cortical control of neuroimmunomodulatory pathways
Authors: Watkins A. D.
Published: May 2008

The central nervous system and the immune system are both stimulus response systems with sophisticated memories mediating defence and adaptation to external and internal threats. There is mounting evidence that these two systems share their information in a bidirectional flow of cytokines, steroids, and neuropeptides. This review examines the influence of higher cognitive centres on immunity and highlights the central role played by the hypothalamus in enabling these two systems to function as an integrated unit to maintain homeostasis. The search for novel compounds that are capable of enhancing immunity by regulating these brain–immune feedback loops offers one of the most exciting areas for future neurobiological research.
Platelet–derived growth factor (PDGF) and receptor (PDGFR) expression in human meningiomas: correlations with clinicopathological features and cytogenetic analysis
Authors: Figarella–Branger D. , Vagner–Capodano A. M. , Bouillot P. , Graziani N. , Gambarelli D. , Devictor B. , Zattara–Cannoni H. , Bianco N. , Grisoli F. , Pellissier J. F.
Published: May 2008

PDGFs and their receptors expression were examined in a series of 46 meningiomas by using specific monoclonal antibodies. The immunostaining was quantified by an image analyser and the results correlated with clinical and morphological data (histological type and grade). In addition, since the PDGFB chain is encoded by the c–sis proto–oncogene localized on chromosome 22 and because monosomy 22 has been frequently reported in meningiomas, PDGFs and PDGFRs expression have been correlated with cytogenetic analysis performed in 29 cases. The results demonstrate PDGF A and PDGFB expression in most meningioma specimens and co–expression of these growth factors in numerous cells. PDGF A and B immunoreactivity was related to histo logical grade. PDGFR βexpression was strong in almost all meningiomas whereas PDGFR α was low. PDGFR α expression was related to tumour location and grade and PDGFR β to histological subtype only. The cytogenetic analysis was not related to PDGFB chain expression. Taken together these data further confirm PDGF and PDGFR expression in human meningioma; PDGF may exist as an heterodimer (AB) as well as its receptor. The lack of correlation between cytogenetic analysis and PDGF values, the low level of PDGFB in recurrent meningiomas suggests that it is unlikely that the c–sis proto–oncogene plays an important role in the genesis of meningiomas.
Selective closure of the vascular bed of an experimental glioma model during in situ saline perfusion
Authors: Luthert P. J. , Greenwood J.
Published: May 2008

Flow through the vasculature of an experimental rat glioma has been investigated during in situ perfusion of the brain, via the ascending aorta, with a simple saline solution. Using such a system, it has been shown previously that the blood–brain barrier will remain intact with an adequate cerebral perfusate flow rate for at least 10 min, providing that the metabolic inhibitor 2,4–dinitrophenol is present. Cerebral perfusate flow rate was measured in both tumour and non–tumour areas using [14C] iodoantipyrine. The perfusion pump rate was set between 4.8 and 84 ml/min in different animals and the mean flow rate for cerebral hemisphere remote from the tumour was 1.03 ± 0.67 ml/min/g (mean ± sd; n= 17) whereas that for intracerebral tumour was considerably lower at 0.060 ± 0.11 ml/min/g (mean ± sd; n= 17). Linear regression of tumour flow on cerebrum flow showed a highly significant correlation (r= 0.88). Light and electron microscope examination of the tumour vessels revealed no luminal obstruction or perivascular oedema to explain the low flow. We suggest that perfusion with a low viscosity medium, at flow rates that result in a low intraluminal pressure, probably causes glioma vessels to close preferentially because they require a higher intraluminal pressure to remain patent than do normal cerebral vessels.
Aspects of canine distemper virus and measles virus encephalomyelitis
Authors: Summers B. A. , Appel M. J. G.
Published: May 2008

Canine distemper (CD) is a frequently fatal, systemic morbillivirus infection in the dog and other carnivores: encephalomyelitis is the common cause of death. Susceptibility to canine distemper virus (CDV) is now recognized in a wide range of non–domestic animals, most recently in captive lions, tigers and leopards. Furthermore, closely related viruses have produced CD–like diseases in marine mammals. CDV induces an inclusion–body encephalomyelitis in the dog and demyelination is often a conspicuous feature. Myelin injury is associated with the presence of virus but the mechanism of demyelination remains incompletely understood. Oligodendrocyte infection may be defective, as has been shownin vitro. CDVand measles virus (MV) produce similar systemic disorders in their respective hosts but differ markedly in the frequency of central nervous system (CNS) involvement, and in the pathogenesis of the more common neurological sequelae. Both CDV and MV have been considered as multiple sclerosis agents, and the association of CDV with other human disease has been suggested.