bluuebunny/crossref_metadata_2025 huggingface dataset:
A new approach to the molecular basis of neoplastic transformation in the brain
Authors: WIESTLER O. D. , BRÜSTLE O. , EIBL R. H. , RADNER H. , DEIMLING A. VON , PLATE K. , AGUZZI A. , KLEIHUES P.
Published: May 2008

Gene transfer into living organisms has evolved as a powerful approach to study in vivo effects of specific genes and to devise animal models of hereditary disorders. We have been particularly interested in an approach to introducing transforming genes into the nervous system. Since specific promoter sequences for targeting the expression of a transgenic to many cell types of the brain are not yet isolated, a suitable transgenic mouse model was not available for these experiments. This has prompted us to develop an alternative strategy for gene transfer into the brain. The rationale is to introduce foreign genes into fetal brain transplants using embryonic CNS as donor tissue and replication‐defective retroviral vectors as genetic vehicles. This technique relies on the extraordinary organotypic differentiation capacity of neural grafts and the expression of retro virally transmitted genes in different cell types of CNS transplants. In contrast to transgenic animals but analogous to sporadic tumour formation, target cells for the retroviral vector will develop in an environment of unmodified neural tissue. We have introduced a number of neurotropic oncogenes into fetal brain transplants to study potential effects of such genes on the brain. This review will summarize some of the findings which have emerged from this experimental study including the tropism of several genes for endothelial cells, attempts to identify cooperating combinations of transforming genes and an experimental model for primitive neuroectodermal tumours in neural grafts.
Pathology of the central nervous system in patients infected with the human immunodeficiency virus (HIV): a Report of 252 autopsy cases from Brazil
Authors: CHIMELLI L. , ROSEMBERG S. , HAHN M.D. , LOPES M.B.S. , NETTO M. BARRETTO
Published: May 2008

The central nervous system (CNS) was studied in 252 HIV‐infected patients from the States of Rio de Janeiro and Sgo Paulo in Brazil, the regions with the highest incidence of AIDS in the country. We compared the frequency and morphology of opportunistic infections and CNS changes caused by the HIV, with those described in other series and briefly analysed the risk factors involved in our cases. There were CNS lesions in 230 cases (91.3%), 30 (11.9%) with multiple infections and/or turnours. Most infections were opportunistic (65.4%), including 15.4% viral and 50% bacterial, fungal or protozoal infections. The most frequent was toxoplas‐mosis (34.1%), followed by cryptococcosis (13.5%), cytomegalovirus (CMV) infection (7.9%) and nodular encephalitis (6.7%). Primary lymphomas were observed in 4% of the cases and HIV encephalitis or leukoencephalopathy in 10.7%. Other opportunistic and HW associated lesions were present in a limited number of cases and there were also vascular and non‐specific lesions. Our study confirms the high frequency of CNS lesions in HIV infected patients. They are morphologically similar to those previously described. However, the higher incidence of toxoplasmosis and cryptococcosis, a lower incidence of viral opportunistic and HIV‐associated lesions, and the presence of rarer lesions such as histoplasmosis and chagasic encephalitis, differ from other series, and may reflect geographical and/or socio‐economic factors.
Immunohistochemical, ultrastructural and immunoelectron microscopic studies of spinal cord neurofibrillary tangles in progressive supranuclear palsy
Authors: KATO S. , HIRANO A. , LLENA J. F.
Published: May 2008

Immunohistochemical, ultrastructural and immunoelectron microscopic studies of spinal cord neurofibrillary tangles (NFTs) in progressive supranuclear palsy (PSP) were performed. The spinal cord NFTs reacted with antibodies to tau protein (tau‐2), ubiquitin and Alzheimer neurofibrillary tangles (ANTs, Ab 39). Ultrastructurally, the NFTs consisted of bundles of straight fibrils. In longitudinal sections, the individual NFT fibrils appeared as straight fibrils with a diameter of approximately 15 nm. In cross sections, circular structures approximately 15 nm in diameter were seen, and some had a central density. Electron microscopic examination of specimens stained with the antibodies and by the modified Bielschowsky method revealed the products of the tau, ubiquitin and ANTs immunoreactions and silver deposits on the NFT fibrils. This is the first demonstration of the ultrastructure of spinal cord NFTs in PSP.
Comparison of modified Bielschowsky silver impregnation and anti‐ubiquitin immunostaining of cortical and nigral Lewy bodies
Authors: LOVE S. , NICOLL J. A. R.
Published: May 2008

We have compared the sensitivity of a modified Bielschowsky silver impregnation with that of anti‐ubiquitin immunostaining for the detection of Lewy bodies in five cases of diffuse Lewy body disease. In two of the cases there were neuritic plaques and neurofibrillary tangles within the neocortex in sufficient numbers to warrant an additional diagnosis of Alzheimer's disease. The modified Bielschowsky technique was as effective as anti‐ubiquitin immunohistochemistry at demonstrating cortical Lewy bodies in 7μm‐thick paraffin sections. As might therefore be expected, silver impregnation of 20μm‐thick sections revealed significantly more cortical Lewy bodies than did the immunostaining of 7μm‐thick sections (P=0.004). The silver impregnation had the further advantage of allowing much better visualization of the Alzheimer‐type changes. In contrast to the cortical‐type Lewy bodies, the dense‐core type present in sections of midbrain were relatively poorly impregnated by the modified Bielschowsky method, possibly reflecting differences in the composition of the two types of inclusion.
Prediction of specific damage or infarction from the measurement of tissue impedance following repetitive brain ischaemia in the rat
Authors: Klein H.C. , Gastel W. Krop‐Van , Go K.G. , Korf J.
Published: May 2008

The development of irreversible brain damage during repetitive periods of hypoxia and normoxia was studied in anaesthetized rats with unilateral occlusion of the carotid artery (modified Levine model). Rats were exposed to 10 min hypoxia and normoxia until severe damage developed. As indices of damage, whole striatal tissue impedance (reflecting cellular water uptake), sodium/ potassium contents (due to exchange with blood), Evans Blue staining (blood‐brain barrier [BBB] integrity) and silver staining (increased in irreversibly damaged neurons) were used. A substantial decrease in blood pressure was observed during the hypoxic periods possibly producing severe ischaemia. Irreversibly increased impedance, massive changes in silver staining, accumulation of whole tissue Na and loss of K occurred only after a minimum of two periods of hypoxia, but there was no disruption of the BBB. Microscopic examination of tissue sections revealed that cell death was selective with reversible impedance changes, but became massive and non‐specific after irreversible increase of the impedance. The development of brain infarcts could, however, not be predicted from measurements of physiological parameters in the blood. We suggest that the development of cerebral infarction during repetitive periods of hypoxia may serve as a model for the development of brain damage in a variety of clinical conditions. Furthermore, the present model allows the screening of potential therapeutic measuring of the prevention and treatment of both infarction and selective cell death.
Zn‐binding globulin in human fetal brain and liver: a marker for passive blood/CSF transfer of protein
Authors: Dziegielewska K. M. , Bell J. E. , Matthews N. , Møllgård K. , Saunders N. R.
Published: May 2008

The presence of Zn‐binding globulin (ZnbG) during human fetal development was studied in cerebrospinal fluid (CSF) and plasma with immunodiffusion methods and in brain, CSF, plasma and liver using immunocytochemical methods. At the earliest stages examined with immuno‐cytochemistry (5–6 weeks gestation) no staining for ZnbG was visible in liver, plasma, CSF or brain. However, the primitive mesenchyme exhibited a prominent staining reaction. In late embryonic and early fetal stages, staining for the protein was most prominent in the spinal cord, brain stem and diencephalon and in the choroid plexuses and marginal and subplate zones in the telencephalon. At the cellular level, synaptic strata and territories were most strongly stained. The distribution of ZnbG in the early developing central nervous system suggests that this protein may be involved in the initial establishment of CNS circuitry. Embryonic brain was positive for ZnbG well before the protein could be detected in CSF, plasma or liver. The early occurrence of ZnbG in brain tissue prior to its presence in liver or plasma also suggests that the protein is synthesized in early fetal brain. At the time when CSF first became positive (17 weeks gestation), the brain staining had largely disappeared. ZnbG in plasma increased throughout gestation to reach 2.6 ± 0.4 mg/100 ml at term and subsequently increased to an adult value of 6.8 ± 1.5 mg/100 ml. The CSF to plasma ratio did not change significantly during development and was low (1–2%) at all fetal ages examined when compared with other plasma proteins; this is consistent with passive transfer between the two compartments both in the fetus and in the adult.
Brown‐Vialetto‐Van Laere Syndrome
Authors: Francis D. A. , Ponsford J. R. , Wiles C. M. , Thomas P. K. , Duchen L. W.
Published: May 2008

The clinical and pathological findings of a male with the Brown—Vialetto—Van Laere syndrome are described. This rare and fatal affection of the nervous system involves mainly the brain stem with the prominent and early manifestation of sensorineural deafness. Increased awareness and documentation of this disorder has added information on the mode of inheritance.
Histochemical and immunocytochemical study of ubiquitinated neuronal inclusions in amyotrophic lateral sclerosis
Authors: Mather K. , Martin J. E. , Swash M. , Vowles G. , Brown A. , Leigh P. N.
Published: May 2008

Ubiquinated cytoplasmic inclusions are a characteristic feature of the anterior horn cell pathology of amyotrophic lateral sclerosis. The underlying abnormality leading to the production of these inclusions in this neurodegenerative motor system disease is unknown. Despite the application of a wide range of histochemical and immunocytochemical techniques we have been unable to identify a core constituent protein in these intraneuronal inclusions. A novel approach to this problem is required.
Corpora amylacea could be an indicator of neurodegeneration
Authors: Singhrao S. K. , Neal J. W. , Newman G. R.
Published: May 2008

We describe an investigation of corpora amylacea (CA) in the brain tissue of Alzheimer's disease (AD) cases and normal ageing controls, using both light (LM) and electron (EM) microscopic techniques. CA populations were shown by routine histological staining of LR White resin sections with methenamine silver and PAS, and were compared with those shown by immunocytochemistry using antibodies to tau, GFAP, tubulin, ubiquitin, β‐amyloid and serum amyloid P component in serial sections. All CA were immunoreactive with anti‐tau and all were unreactive with anti‐β‐amyloid. Most were immunoreactive with anti‐serum amyloid P component, although this was often weak in AD. CA from normal ageing brain were immunoreactive for proteins that are associated with the neuronal cytoskeleton and cell injury. CA from AD brain shared some of these but differed from those in normal ageing brain by being in much larger number and more variable in their immunoreactivity. In all CA, X‐ray microanalysis illustrated the presence of the metallic elements Ca, Fe and Cu. Aluminium, often associated with AD, was not present, even in CA from AD brain. Phosphorus and sulphur, probably from phosphorylated proteins associated with degenerating cytoskeleton elements, were usually detected. In AD brain, the greater numbers of CA and their variable biochemical and elemental composition, when compared with CA in the normal ageing brain, suggests that they may derive from a number of sources both neuronal and glial as a result of the neurodegenerative disease.
IDPN impairs post‐traumatic regeneration of rat sciatic nerve
Authors: Morbin M. , Monaco S. , Zanette G. , Rizzuto N.
Published: May 2008

The role played by cytoskeletal proteins in nerve regeneration was investigated in a model in which the axonal transport of neurofilaments (NF) is almost selectively impaired. The administration of β, β‐iminodipropionitrile (IDPN), a synthetic lathyrogenic compound, induces an axonopathy characterized by proximal axonal enlargements, due to NF accumulation, and by diffuse atrophic changes associated with spatial segregation of NF from microtubules (MT). We investigated post‐axotomy regeneration of rat sciatic nerve following IDPN administration. Changes induced by IDPN, as examined in the proximal and distal nerve stump at 15 and 30 days after lesion, consisted of a statistically significant reduction of the mean axonal diameter (P < 0.0001) as compared to control rats. In addition, the number of regenerating myelinated fibres was smaller in dosed rats (P < 0.001) 15 days after crush, whereas at the later stage the number of axons approached that of control animals. Electrophysiological investigation revealed a delay in target reinnervation in dosed rats. Regenerating IDPN axons, both 15 and 30 days after crush contained fewer NF (P < 0.001), while the number of MT was slightly increased as compared to controls. Taken together, our results suggest that severe alteration of NF transport, coupled with mild alteration of other components of cytoskeletal proteins, impairs the longitudinal and radial growth of regenerating myelinated axons and confirm that the number of NF is the major determinant of the cross‐sectional area of each segment of the axon.
Oedema‐related tissue damage after temporary and permanent occlusion of the middle cerebral artery
Authors: Nordborg C. , Sokrab T.E.O. , Johansson B.B.
Published: May 2008

Oedema‐related tissue damage after temporary and permanent occlusion of the middle cerebral arteryEleven adult spontaneously–hypertensive male rats (SHR) were studied 2 2 h or 7 days after a 2 h unilateral occlusion of the right middle cerebral artery (MCA). Another 11 SHR were studied after 24 h or 7 days of permanent MCA ligation. The brain infarcts were significantly larger (P < 0.05) after permanent occlusion than after a 2h occlusion. More extensive and widespread vasogenic oedema, emanating from the infarcts, was visualized immunohistochemically in the temporarily–ligated animals and the relative number of astrocytes in their contralateral hemispheres was greater, thereby indicating that the vasogenic oedema influences the degree of gliosis. An immunopositivity for albumin but not for fibrinogen extended via the white matter into the ipsilateral thalamic nuclei, where cytolytic nerve cell damage, severely shrunken and karyorrhectic nerve cells as well as gliosis were found one week after permanent and temporary MCA ligation. The histological changes in the thalamus indicated a difference in timing between lateral and medial parts of the lesion as well as between temporarily–and permanently–ligated SHR. These findings together with the close spatial correlation with albumin immunoreactivity indicate that the spread of extravasated plasma constituents or degradation products with the oedema bulk flow from the infarct influences the timing, character and extent of thalamic lesions after cerebral infarction.
New immunocytochemical evidence for a neuronal/oligodendroglial origin for corpora amylacea
Authors: Singhrao S. K. , Neal J. W. , Piddlesden S. J. , Newman G. R.
Published: May 2008

New immunocytochemical evidence for a neuronal/oligodendroglial origin for corpora amylaceaStudies employing a bank of antisera applied to sections of LR White embedded AD and normal ageing brain tissue, may throw new light on the derivation of CA. Conspicuous levels of immunoreactivity were found in the CA of both tissues with markers for oligodendrocytic proteins such as antisera against myelin basic proteolipid protein, galacto–cerebroside and myelin/oligodendrocyte glycoprotein. CA were unreactive with MRC OX–42, a marker for microglia and macrophages. In a previous publication [22] we demonstrated that the much more abundant CA in the brains of Alzheimer's disease (AD) sufferers, although slightly more varied in their immunoreactivity than those found in normally ageing controls, were universally immunoreactive with anti–tau, a neuronally derived protein and often also contained amyloid. The cores of CA were not immunoreactive with anti–GFAP, suggesting a lack of involvement with astrocytes. Our results now show that in addition to amyloid and neuronal proteins, a significant proportion of the content of CA is derived from oligodendrocytes and/or myelin. The substantial Fe peak previously reported [22] following X–ray microanalysis of CA was probably due to ferritin. However, immuno–staining with antisera to ferritin showed that high ferritin immunoreactivity was common to both micro– and macroglia as well as CA. More significantly, the immunoreactivity of CA with anti–ubiquitin [22] suggests that degeneration of neuronal/oligodendrocytic elements may precede CA formation.
Meeting report
Authors: Kirk Dr J.
Published: May 2008

Blood–Brain Barrier Workshop, Portrush, County Antrim, Northern Ireland, 2 October 1993 (Sponsored by the Multiple Sclerosis Society of Great Britain and Northern Ireland and by Neuropathology and Applied Neurobiology)
Herpes simplex virus type 1 gene expression and reactivation of latent infection in the central nervous system
Authors: Steiner I. , Mador N. , Reibstein I. , Spivack J. G. , Fraser N. W.
Published: May 2008

Restricted gene expression takes place during latent infection of herpes simplex virus type 1 (HSV–1) in the human peripheral nervous system and has been linked with viral reactivation. The state of HSV–1 gene expression in the central nervous system (CNS) during latency is unclear and we. therefore, examined gene expression in the brainstem of experimental mice and normal humans. Only part of the transcription pattern present during latent infection in peripheral sensory ganglia (PSG) was identified in the human brainstem by in situ hybridization and Northern blot analysis for HSV–1–specific transcripts. Instead of three HSV–1 latency associated transcripts (LATs) present in PSG and demonstrated by Northern blot analysis, only one was identified in mouse brainstem and none was detected in human brainstem. These findings might be attributed to the relatively low amounts of HSV–1–specific latency–associated RNAs in brainstem tissue. Combined with our inability to reactivate HSV–1 from explanted mouse brainstem, these findings suggest that tissue levels of latency–associated gene expression play a role in HSV–1 reactivation and have relevance to the very low incidence of HSV–1–induced CNS disease compared with peripheral mucocutaneous disease.
A morphological and functional assessment of Mycobacterium leprae‐induced nerve damage in a guinea‐pig model of leprous neuritis
Authors: de Blaquiere G. E. , Santamaria L. , Curtis J. , Terenghi G. , Polak J. M. , Turk J. L.
Published: May 2008

Nerve damage, resembling that caused by Mycobacterium leprae in man, was created by the injection of cobalt–irradiated M. leprae organisms into the tibial nerve of guinea–pigs. Assessment of nerve damage was made by clinical, electrophysiological and morphometric means at intervals up to 13 weeks after injection. Quantitative immunohistochemical analysis of neuropeptide–containing fibres in the skin of the foot was also carried out. Significant nerve damage occurred 3 weeks after injection of M. leprae organisms. Motor and sensory functional loss peaked at 5 weeks after injection, and there was a significant decrease of peptide–immunoreactive nerves in all skin compartments. The nerve damage was self–limiting and functional recovery had occurred by 13 weeks. The model shows many of the features found in the nerve damage of treated leprosy patients.
A modified NOR–silver impregnation technique for amyloid plaques and neurofibrillary tangles: comparative assessment
Authors: Abe H. , Mehraein P. , Weis S.
Published: May 2008

A modified nucleolar organizer region (NOR)–silver impregnation technique was recently introduced allowing the simultaneous staining of neurofibrillary tangles (NFT) and amyloid plaques (AP) in a single section. This impregnation technique proved to be very effective, rapid, of low cost, and to yield consistent results even in brain tissue fixed for long periods of time. In the present study, several silver impregnation and immunohis–tochemical techniques were applied and their reliability for the demonstration of NFT and AP was analysed. The modified NOR stain allowed the reliable and simultaneous demonstration of both amyloid plaques and neurofibrillary tangles; this method produced better results than the standard silver impregnation techniques. It is only in their early stages of formation that NFT cannot be detected by this method and, instead. immunohistochemistry for tau–2 is required. There was no significant difference in the staining properties for amyloid plaques between the modified NOR silver impregnation technique and the anti–β–A4 immunostain.
Freeze–fracture analysis of muscle plasma membrane in Becker's muscular dystrophy
Authors: Shibuya S. , Wakayama Y. , Jimi T. , Oniki H. , Kobayashi T. , Misugi N. , Kumagai T. , Hasegawa O. , Suzuki Y. , Kuroiwa Y.
Published: May 2008

The intramembranous particle (IMP), orthogonal array (OA) and orthogonal array subunit particle (OASP) densities in skeletal muscle plasma membranes from eight patients with Becker*s muscular dystrophy (BMD) were analysed by the freeze–fracture technique. The results showed almost normal IMP density with the significant decrease of OA and OASP densities in BMD. The group mean densities ± SE of IMPs on the protoplasmic faces with and without OASPs, and on extracellular faces/μm2 were 2137 ± 207, 1839 ± 68 and 895 ± 108, respectively in controls; whereas those of BMD were 1989 ± 259, 1837 ± 203 and 900 ± 239, respectively (P > 0.1 by two–tailed t–test). The group median density of OAs and their pits/nm2 was 4.89 with mid–ranges (25˜75% values of the counts) of 2.66 ˜ 10.18 in controls; whereas that in BMD was 2.15 with mid–ranges of 1.14 ˜ 4.31 (P < 0.01 by Wilcoxon rank–sum test). The group mean density ± SE of OASPs in controls was 15.99 ± 1.83; whereas that in BMD was 13.47 ± 1.07 (P < 0.01 by two–tailed t–test). However, the diminution of OA and OASP densities in BMD muscle plasma membranes was not as severe as in Duchenne's muscular dystrophy. There was a relationship between OA density and clinical severity in BMD patients; the decrease of OA density in a severe BMD patient was more marked than that in mildly affected BMD patients. Therefore, it seems that marked depletion of OA density may lead to the severe disability in muscular dystrophies.
Detection of multidrug resistance gene product (P‐glycoprotein) expression in ependymomas
Authors: Geddes J. F. , Vowles G. H. , Ashmore S. M. , Cockburn H. A. , Darling J. L.
Published: May 2008

A neurosurgical series of 33 ependymal tumours was examined for expression of the membrane transport molecule P‐glycoprotein, which is linked with the development of multidrug resistance in many human tumours. We employed the monoclonal antibodies JSB1 and C219, raised to two different epitopes of the P‐glycoprotein molecule, and found P‐glycoprotein expression both in normal ependyma and in 29 of the tumours. This is the first time that ependymal tumours have been demonstrated to express the protein, and we conclude that its expression may contribute to the reported failure of adjuvant chemotherapy to improve outcome in ependymomas.
Oxidative stress in Parkinson's disease
Authors: Schapira A. H. V.
Published: May 2008

Oxidative damage and mitochondrial dysfunction are now considered to be important events in the cause of dopaminergic cell death in Parkinson's disease (PD). It is not known whether these biochemical abnormalities represent primary causes of PD or whether they are the end result of a series of reactions precipitated by environmental and genetic factors. Both oxidative damage and complex 1 deficiency are linked in a reciprocal manner and can potentially produce a toxic cellular environment capable of attacking a variety of biomolecules as well as inhibiting energy production. Defining the roles that these two biochemical defects play in nigral neuronal loss will provide important insights into the aetiology of PD.
Distribution of β‐amyloid protein in the brain following severe head injury
Authors: Graham D. I. , Gentleman S. M. , Lynch A. , Roberts G. W.
Published: May 2008

Deposits of β‐amyloid protein (PAP) can be found in the brains of 30% of fatally head‐injured patients: they have been found in children and after survival times of only 4 h. The principal aims of this study were to map the distribution of βAP in 14 patients aged 65 years or less in whom it was known that the protein had been deposited, and to correlate its distribution with the pathologies of traumatic brain injury. The results show that βAP is widely distributed, and that there is no correlation between its presence and cerebral contusions, intracranial haematoma, axonal injury, ischaemic brain damage, brain swelling or the pathology of raised intracranial pressure. These findings suggest that the deposition of βAP is a consequence of the acute phase response of nerve cells to stress in susceptible individuals. Further studies will be required to establish the possible relationship between the deposition of βAP following head injury and the molecular neuropathology of Alzheimer's disease.
Neurodegeneration in the limbic and paralimbic system in progressive supranuclear palsy
Authors: Higuchi Y. , Iwaki T. , Tateishi J.
Published: May 2008

Progressive supranuclear palsy is neuropathologically characterized by neuronal degeneration of the basal ganglia, brain stem, and cerebellum. In addition, cortical neuronal degeneration associated with neurofibrillary tangles formation has been identified over wide areas of the brain in patients with progressive supranuclear palsy. We studied the distribution of αB‐crystallin‐positive degenerating neurons in cases with progressive supranuclear palsy, and compared them with those in Pick's disease, Alzheimer's disease, senile dementia of Alzheimer type, and normal aged individuals. A large number of αB‐crystallin‐positive neurons was found in the cerebral cortices of four out of nine patients with progressive supranuclear palsy. In particular, αB‐crystallin‐positive ballooned neurons were frequently observed in deep cortical pyramidal cell layers of the limbic and paralimbic systems in these diseases. The involvement of the limbic and paralimbic systems may thus contribute to personality changes as well as to memory and cognitive impairment in some patients with progressive supranuclear palsy.
The response of neurons and microglia to blast injury in the rat brain
Authors: Kaur C. , Singh J. , Lim M. K. , Ng B. L. , Yap E. P. H. , Ling E. A.
Published: May 2008

Rats subjected to a single non‐penetrative blast were examined for possible neuronal damage and glial reaction by immunohistochemistry and electron microscopy. The most dramatic feature in rats killed between 1 and 14 days after the blast was the widespread response of microglial cells in various parts of the brain in which the cells were hypertrophied and their surface antigens, like complement type three receptors (CR3), were upregulated. The blast wave also induced the vigorous expression of major histocompatibility complex (MHC) class I and II (Ia) antigens. In rats killed 21 days after the blast, the elevated immunoreactivity of microglia had subsided and at 28 days both the microglial external morphology and immunoreactivity were comparable to those of normal animals. In rats killed 4–7 days after the blast, the neurons in the cerebral and cerebellar cortex appeared normal except for the occurrence of some ‘darkened dendrites’. The incidence of ‘darkened’ den‐drites was most common in rats killed at day 14 but they were absent at 21 and 28 days. Microglial cells were closely associated with some of the ‘darkened’ dendrites.

Results in this study show that a non‐penetrative blast in rats provokes a widespread microglial activation suggesting increased endocytosis and immunological responses. However, it remains uncertain whether such a drastic response was a direct activation of the cells by the blast wave or elicited indirectly by some chemical factors released from the damaged brain tissues.
Cytochrome c oxidase deficiency in zidovudine myopathy affects perifascicular muscle fibres and arterial smooth muscle cells
Authors: Chariot P. , Mague F. Le , Authier F. J. , Labes D. , Poron F. , Gherardi R.
Published: May 2008

In order to assess the pathogenesis of myopathological alterations induced by zidovudine, we studied muscle samples from 21 patients infected by human immunodeficiency virus with zidovudine myopathy. Cytochrome c oxidase histoenzymatic reaction was evaluated in slreletal muscle fibres and arterial smooth muscle cells. Other investigations included immunocytochemistry for membrane attack complex and endomysial capillary counts. All patients had partial cytochrome c oxidase deficiency. A perifascicular distribution of cytochrome c oxidasedeficient fibres was found in 14 of 21 patients. Cytochrome c oxidase‐deficient fibres were significantly more frequent in perifascicular areas than in the complete muscle sections (28% vs 12%, P<0.001). Cytochrome c oxidase‐deficient arteries were found in 11 patients, of whom 10 also had a perifascicular deficiency. Mono‐nuclear microvascular inflammation was obsenred in four patients and membrane attack complex deposition in capillary walls in two patients. The capillary counts were not significantly different in the patients and in the controls. These results suggest that, in addition to a direct action of zidovudine on mitochondrial DNA, chronic muscle ischaemia related to zidovudine‐induced vascular dysfunction might be implicated at the inception of muscle damage in zidovudine myopathy.
Wernicke's encephalopathy with ballooned neurons in the mamillary bodies: an immunohistochemical study
Authors: Freiesleben W. , S|f‐ylemezoglu F. , Lowe J. , Janzer R. C. , Kleihues P.
Published: May 2008

Two cases of Wernicke's encephalopathy with the rare phenomenon of ballooned neurons in the mamillary bodies are reported. Both patients suffered from acute Wernicke's symptoms starting approximately two weeks before death. The mamillary bodies contained grossly enlarged, ballooned neurons, in one case associated with focal necrosis. The affected neurons were immunoreactive for phosphorylated neurofilament (160 and 200 kDa), and synaptophysin. Ubiquitin and αβ crystallin expression were not detected. The mamillothalamic tract appeared normal in both cases. There was a marked associated microglial reaction, as shown by the antibody Ki‐M1P. It is concluded that the ballooning of mamillary neurons reflects an acute retrograde reaction to primarily axonal damage. Rather than being a rare manifestation of the disease, these cases may constitute a typical intermediate early stage (10–15 days) in the development of Wernicke's encephalopathy.
Expression of cell adhesion molecules by microvascular endothelial cells in the cortical and subcortical regions of the normal human brain: an immunohistochemical analysis
Authors: Navratil E. , Couvelard A. , Rey A. , Hénin D. , Scoazec J.‐Y.
Published: May 2008

We studied the repertoire of junctional, cell–matrix and leucocyte–endothelial adhesion molecules normally expressed by cortical and subcortical brain microvessels, as compared with large intracranial vessels. An indirect immunoperoxidase method was applied to acetone‐fixed cryostat sections of normal brain tissue obtained from 10 adult patients during surgical resections for intracranial aneurysms or at autopsy. Like large intracranial vessels, brain microvessels expressed the two endothelial‐specific junctional cell adhesion molecules VE‐cadherin and platelet–cell adhesion molecule‐1. We verified that they also expressed the molecular components of adherens‐type junctions, including catenins, plakoglobin, vinculin and α‐actinin. Brain microvessels expressed a large repertoire of integrin molecules of the β1, β3 and β4 subfamilies. However, they displayed apparently lower levels of α2, α5, αV and β3 integrin chains than large intracranial vessels. Brain microvessels constitutively expressed large amounts of the leucocyte–endothelial adhesion molecules, intercellular adhesion molecule (ICAM)‐2 and CD34 and very low amounts of ICAM‐1 and lymphocyte function‐associated antigen‐3. In contrast to large intracranial vessels, brain microvessels presented no constitutive expression of P‐selectin. Our study shows that, in contrast to their highly specific structural and functional characteristics, brain microvascular endothelial cells present a repertoire of cell adhesion molecules very similar to that of most other capillary vessels in the body.
Role of high molecular weight extracellular matrix proteins in glioma cell migration
Authors: Mahesparan R. , B. Tysnes B. , Edvardsen K. , Haugeland H. K. , Garcia Cabrera I. , Lund‐Johansen M. , Engebraaten O. , Bjerkvig R.
Published: May 2008

Malignant human gliomas are characterized by an uncontrolled cell proliferation and infiltrative growth within the brain. Complete surgical removal is difficult due to disseminated tumour cells, and the fundamental mechanisms responsible for this spread are poorly understood. An extensive tumour cell movement along blood vessels is frequently observed and this may be due to specific interactions between tumour cell surface receptors and specific extracellular matrix (ECM) components present in conjunction with vascular elements. In order to investigate the influence of ECM on glioma cell migration, three different human glioma cell lines (U‐373 MG, A‐172 MG and HF‐66) were exposed to known ECM components of the basement membrane (laminin, fibronectin and collagen type IV). Cell migration from multicellular spheroids was studied, using a custom‐made medium which was prepared by removing the high molecular weight protein fraction (>100 kDa) from newborn calf serum by ultrafiltration. To this medium, the specific ECM components were added. For two of the cell lines (A‐172 MG and U‐373 MG), laminin was the most potent stimulator of glioma cell migration; the effect of laminin exceeded that evoked by ordinary serum‐supplemented medium. For the HF‐66 cell line, fibronectin was the most potent stimulator of migration. Western blot analysis showed that the A‐172 MG and HF‐66 cell lines expressed low amounts of laminin compared with U‐373 MG, which showed extensive intrinsic synthesis of this ligand. U‐373 MG was the only cell line that migrated in pure filtered medium. The cells stimulated by fibronectin expressed a different morphology from those stimulated by laminin suggesting that specific ECM‐receptor binding may activate different cytoskeletal components within the cells. Furthermore, it was shown that there was no difference in the amount of protein synthesis between cells grown in filtered medium and in filtered medium supplemented with different ECM components. This suggests that ECM‐induced cell migration is not dependent on a high level of protein synthesis. It is also shown that α3 integrin, which is a receptor‐subunit for laminin, fibronectin and collagen type IV, was highly expressed in all cell lines. This study indicates that glioma cells need serum proteins with a molecular weight >100 kDa to migrate in vitro, and that laminin and fibronectin play an important role in this process.
Interleukin‐1 expression in inflammatory myopathies: evidence of marked immunoreactivity in sarcoid granulomas and muscle fibres showing ischaemic and regenerative changes
Authors: Authier F. J. , Mhiri C. , Chazaud B. , Christov C. , Cherin P. , Barlovatz‐Meimon G. , Gherardi R. K.
Published: May 2008

The most frequent autoimmune adult inflammatory myopathies are dermatomyositis, polymyositis, inclusion body myositis, and sarcoid myopathy. Interleukin‐1 (IL‐1) is a pleiotropic molecule, implicated in the inflammatory process, but also in tissue protection and remodelling. We evaluated the immunocytochemical expression of IL‐1α and β in frozen muscle biopsy specimens from patients with dermatomyositis (15 cases), polymyositis (five cases), inclusion body myositis (five cases) and sarcoid myopathy (five cases). Positive immunoreactivities, were observed in both inflammatory cells and muscle fibres. Specificity of the immunostaining was assessed by Western blot experiments. IL‐1 positive inflammatory cells were rare in polymyositis and inclusion body myositis, moderately abundant in dermatomyositis, and prominent in sarcoid myopathy granulomas. In sarcoid myopathy, 24.6±4.1% inflammatory cells were IL‐1α‐positive and 45.2±2.6% were IL‐1β‐positive. IL‐1 positive muscle fibres were mainly observed in dermatomyositis, usually remote from inflammatory infiltrates. Positive immunostaining for IL‐1 was observed in fibres showing ischaemic punched‐out vacuoles, that correspond to areas of myosinolysis, in atrophic perifascicular fibres, and in fibres located within healing microinfarcts. All NCAM‐positive regenerating fibres were IL‐1 positive. We conclude that: (i) IL‐1 is expressed in granulomas of sarcoid myopathy, which is in keeping with the role ascribed to IL‐1 in the formation of granulomas; (ii) IL‐1 is expressed by muscle fibres undergoing ischaemic damage; and (iii) IL‐1 expression by muscle fibres is associated with myofibrillar protein breakdown and regeneration.
DNA‐fragmentation and expression of apoptosis‐related proteins in muscular dystrophies
Authors: Tews D. S. , Goebel H. H.
Published: May 2008

Although numerous sarcolemmal protein defects in muscular dystrophies have been identified, the mechanisms linking these defects and muscle fibre degeneration are not fully characterized. As there is evidence that apoptosis is part of muscle fibre loss in dystrophin‐deficient mdx‐mice, apoptotic muscle fibre death may also play a role in humans with muscular dystrophies. We investigated in‐situ DNA‐fragmentation by the TUNEL‐method and expression of apoptosis‐related proteins immunohistochemically in 14 children suffering from deficiencies of dystrophin, adhalin, and merosin, and found TUNEL‐positive chromatin‐cleavage of muscle fibre nuclei in about 10% of non‐necrotic muscle fibres. DNA‐fragmentation also occurred in groups of ‘necrotic and regenerating’ muscle fibres with labelling of nuclei in myogenic cells and phagocytizing macrophages. These lesions also revealed expression of apoptosis‐promoting factors, such as bax and ICE, inducing cleavage of myofilaments, and of the apoptosis‐inhibiting proteins bcl‐xL and bcl‐2 which neutralized high bax levels. Mimicking embryonal myogenesis, chromatin‐fragmentation in ‘necrotic and regenerating’ areas seems to be part of the regulating events in muscle regeneration to eliminate excessive proliferating satellite cells. Nevertheless, macrophages are also affected by apoptosis after successful removal of necrotic fibres. In humans, DNA‐fragmentation and expression of apoptosis‐related proteins indicate that apoptosis plays a role in muscle degeneration and regeneration in muscular dystrophies.
IL‐27‐Mediated Activation of Natural Killer Cells and Inflammation Produced Antitumour Effects for Human Oesophageal Carcinoma Cells
Authors: Liu L. , Wang S. , Shan B. , Shao L. , Sato A. , Kawamura K. , Li Q. , Ma G. , Tagawa M.
Published: May 2008

Interleukin (IL)‐27, composed of p28 and EBV‐induced gene 3 subunits, has diverse functions in enhancing cell‐mediated immunity and silencing the immunity. We examined whether forced expression of the p28‐linked EBI3 gene in human oesophageal carcinoma cells (Eca109) produced antitumour effects in a T cell‐defective condition. Tumour growth of Eca109 cells expressing IL‐27 (Eca109/IL‐27) was retarded in nude mice compared with parental and vector DNA‐transduced tumours and survival of the mice inoculated with Eca109/IL‐27 cells was prolonged. Expression of the tumour necrosis factor‐α, IL‐1β and IL‐6 genes was up‐regulated in Eca109/IL‐27 tumour specimens while the tumours remained small in size but the increased transcription was subsequently down‐regulated in enlarged tumours. Spleen cells from mice‐bearing Eca109/IL‐27 tumours produced interferon‐γ and showed YAC‐1‐targeted cytotoxic activities greater than those of mice inoculated with parental or vector DNA‐transducer tumours. Numbers of DX5+CD69+ natural killer cells in spleen of mice‐bearing Eca109/IL‐27 tumours and those of CD31+ cells within Eca109/IL‐27 tumours remained the same as found in mice‐bearing parental or vector DNA‐transduced tumours. These data collectively suggest that the IL‐27‐mediated antitumour effects produced in a mature T cell‐defective condition were attributable to enhanced interferon‐γ production and natural killer activities.
High‐value oils from plants
Authors: Dyer John M. , Stymne Sten , Green Allan G. , Carlsson Anders S.
Published: May 2008

The seed oils of domesticated oilseed crops are major agricultural commodities that are used primarily for nutritional applications, but in recent years there has been increasing use of these oils for production of biofuels and chemical feedstocks. This is being driven in part by the rapidly rising costs of petroleum, increased concern about the environmental impact of using fossil oil, and the need to develop renewable domestic sources of fuel and industrial raw materials. There is also a need to develop sustainable sources of nutritionally important fatty acids such as those that are typically derived from fish oil. Plant oils can provide renewable sources of high‐value fatty acids for both the chemical and health‐related industries. The value and application of an oil are determined largely by its fatty acid composition, and while most vegetable oils contain just five basic fatty acid structures, there is a rich diversity of fatty acids present in nature, many of which have potential usage in industry. In this review, we describe several areas where plant oils can have a significant impact on the emerging bioeconomy and the types of fatty acids that are required in these various applications. We also outline the current understanding of the underlying biochemical and molecular mechanisms of seed oil production, and the challenges and potential in translating this knowledge into the rational design and engineering of crop plants to produce high‐value oils in plant seeds.
Production of renewable polymers from crop plants
Authors: Van Beilen Jan B. , Poirier Yves
Published: May 2008

Plants produce a range of biopolymers for purposes such as maintenance of structural integrity, carbon storage, and defense against pathogens and desiccation. Several of these natural polymers are used by humans as food and materials, and increasingly as an energy carrier. In this review, we focus on plant biopolymers that are used as materials in bulk applications, such as plastics and elastomers, in the context of depleting resources and climate change, and consider technical and scientific bottlenecks in the production of novel or improved materials in transgenic or alternative crop plants. The biopolymers discussed are natural rubber and several polymers that are not naturally produced in plants, such as polyhydroxyalkanoates, fibrous proteins and poly‐amino acids. In addition, monomers or precursors for the chemical synthesis of biopolymers, such as 4‐hydroxybenzoate, itaconic acid, fructose and sorbitol, are discussed briefly.
Harnessing plant trichome biochemistry for the production of useful compounds
Authors: Schilmiller Anthony L. , Last Robert L. , Pichersky Eran
Published: May 2008

Plant trichomes come in a variety of shapes, sizes and cellular composition. Some types, commonly called glandular trichomes, produce large amounts of specialized (secondary) metabolites of diverse classes. Trichomes are implicated in a variety of adaptive processes, including defense against herbivores and micro‐organisms as well as in ion homeostasis. Because trichomes protrude from the epidermis and can often be easily separated from it and harvested, the mRNAs, proteins and small molecules that they contain are unusually accessible to analysis. This property makes them excellent experimental systems for identification of the enzymes and pathways responsible for the synthesis of the specialized metabolites found in these structures and sometimes elsewhere in the plant. We review the literature on the biochemistry of trichomes and consider the attributes that might make them highly useful targets for plant metabolic engineering.
Biosynthesis of plant‐derived flavor compounds
Authors: Schwab Wilfried , Davidovich‐Rikanati Rachel , Lewinsohn Efraim
Published: May 2008

Plants have the capacity to synthesize, accumulate and emit volatiles that may act as aroma and flavor molecules due to interactions with human receptors. These low‐molecular‐weight substances derived from the fatty acid, amino acid and carbohydrate pools constitute a heterogenous group of molecules with saturated and unsaturated, straight‐chain, branched‐chain and cyclic structures bearing various functional groups (e.g. alcohols, aldehydes, ketones, esters and ethers) and also nitrogen and sulfur. They are commercially important for the food, pharmaceutical, agricultural and chemical industries as flavorants, drugs, pesticides and industrial feedstocks. Due to the low abundance of the volatiles in their plant sources, many of the natural products had been replaced by their synthetic analogues by the end of the last century. However, the foreseeable shortage of the crude oil that is the source for many of the artifical flavors and fragrances has prompted recent interest in understanding the formation of these compounds and engineering their biosynthesis. Although many of the volatile constituents of flavors and aromas have been identified, many of the enzymes and genes involved in their biosynthesis are still not known. However, modification of flavor by genetic engineering is dependent on the knowledge and availability of genes that encode enzymes of key reactions that influence or divert the biosynthetic pathways of plant‐derived volatiles. Major progress has resulted from the use of molecular and biochemical techniques, and a large number of genes encoding enzymes of volatile biosynthesis have recently been reported.