bluuebunny/crossref_metadata_2025_split huggingface dataset:
UNUSUAL DEVELOPMENT OF POLYOMA VIRUS IN THE BRAINS OF TWO PATIENTS WITH THE ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)
Authors: SCARAVILLI F. , ELLIS D. S. , TOVEY G. , HARCOURT–WEBSTER J. N. , GUILOFF R. J. , SINCLAIR E. 
Published: May 2008

Two HIV–positive male patients presented with a variety of symptoms including hemiparesis, unsteadiness, progressive loss of vision and poor memory. There were multiple non–enhancing lesions shown by CT scan in the white matter of the cerebral hemispheres. Specimens obtained by burr–hole biopsy showed the features of progressive multifocal leucoencephalopathy (PML) in both cases. Electron microscopy demonstrated round and rod shaped particles of papovavirus in the nuclei and cytoplasm of oligodendrocytes and in processes of astrocytes where abnormal and florid modes of viral replication were seen. Additional features observed were viral particles suggestive of an enterovirus in Case 1 and, in both specimens, massive membrane proliferation within both nuclei and cytoplasm of infected cells together with the presence of tubuloreticular structures (TRS) in the cytoplasm of endothelial cells. At post–mortem, the brain of patient 2 showed PML and HIV encephalitis. The presence of HIV was confirmed by immunohistochemical methods.We suggest that in AIDS patients the abnormality of the immune system induced by HIV causes abnormal replication patterns of papovavirus in the brain. In addition, these cases confirm the frequent occurrence in AIDS patients of TRS, now considered to be a marker for HIV.
EXPERIMENTAL TRACTION INJURIES OF VENTRAL SPINAL NERVE ROOTS. A SCANNING ELECTRON MICROSCOPIC STUDY
Authors: BRISTOL D. C. , FRAHER J. P. 
Published: May 2008

The aims of this experimental scanning electron microscopic study were to identify the levels at which cervical ventral nerve roots, or the rootlets by which they are attached to the spinal cord, rupture under traction and to document the resulting damage. This information would provide the basis of a rationale for repairing rootlet avulsions which may follow brachial plexus traction injuries in man and which cause severe impairment of upper limb function.Traction was applied to C4 to Tl ventral roots until rupture occurred, in 10 freshly fixed and three living anaesthetized Wistar albino rats and in one human post–mortem specimen. Rupture occurred at the rootlet–cord junction in 80% of cases. Most individual myelinated fibres broke at the central–peripheral nervous system (CNS–PNS) transitional node which, in the cervical region, lies at the bottom of an endoneurial invagination surrounding each fibre and extending deep to the cord surface. Fibre rupture at more distal levels occurred internodally, and a length of axon commonly protruded well beyond the level of sheath rupture. Some sheaths broke cleanly across but the torn surfaces of others tapered, perhaps because of rupture at Schmidt–Lanterman incisures. The cellular and connective tissue rootlet sheaths ruptured where they were continuous with the pia mater. Ruptured fixed and unfixed tissues were ultrastructurally similar.It is clear from the findings of this study that regeneration would take place entirely in a PNS environment. The endoneurial invaginations would ensure that sprouts emerging from transitional nodes would be guided distally into rootlets surgically apposed to the torn transitional zone.
Kinetics and glial fibrillary acidic (GFA) protein production in a transplantable human giant cell glioblastoma (D‐212 MG) of near haploid karyotype maintained in an organ culture system. An immunohistochemistry study
Authors: IBAYASHI N. , HERMAN M. M. , BOYD J. C. , CACCAMO D. V. , FRIEDMAN H. S. , BIGNER D. D. , RUBINSTEIN L. J. 
Published: May 2008

A transplantable subcutaneous tumour (designated D‐212 MG), sequentially passaged in athymic nude mice and originally derived from a human giant cell glioblastoma, was maintained in an organ culture (matrix) system and studied immunohistochemically after in vitro pulse‐labelling with bromodeoxyuridine (BrdU) and for the presence of glial fibrillary acidic (GFA) protein, after 1, 2 and 3 weeks in culture. The histological characteristics of the tumour, showing two cell populations of giant multinucleated cells and small cells, were preserved in the explants.An increased percentage of multinucleated giant cells was found after 3 weeks in vitro. A small but constant fraction (4–6%) of these cells continued to synthesize DNA. The labelling index of the small cells was somewhat higher, but decreased slightly although significantly over the 3‐week period in vitro (from approximately 10.5 to 8%). The percentage of small cells that were positive for GFA protein was in the region of 75% and that of the giant multinucleated cells was in the region of 45%; it did not change significantly during the 3 weeks in vitro.The in vitro results confirm the astrocytic nature of both the small cells and the giant multinucleated cells in this tumour, the capacity of both cell populations to synthesize DNA in culture and to demonstrate invasiveness, and suggest the possibility that some of the giant multinucleated cells may have originated from the conversion of a number of small tumour cells.
Influence of host sex on the growth of a human glioblastoma line in athymic mice
Authors: VERZAT C. , DELISL M. B. , COURRIERE P. , HOLLANDE E. 
Published: May 2008

Glioblastomas are generally thought to be more common in men than in women. In erder to investigate the hormone‐dependence of these tumours, we established a human glioblastoma line in athymic mice. The tumour cell type was characterized using immunocyto‐chemical methods. The influence of host sex on growth was evaluated, and hormone receptors were characterized biochemically.The histological features of the initial tumour were conserved in the hetero‐transplanted tumours, which consisted of vimentin and GFAP immunoreactive astrocytes. There was a highly significant difference in tumour growth between the two sexes (P < 0.01). In the male mice, tumours were from 2.5 to 10 times larger than in the females, the latency periods were 30% shorter, and the growth phases were characterized by periods of slow or zero growth. In addition, androgen and oestrogen receptors were detected at low levels (80–270 fmol/g tumour) in the heterotransplanted tumours especially in the males. The fact that the male tumour growth profiles resembled those of some hormone‐dependent lines, and that androgen receptors were found preferentially in the male rather than in female tumours would tend to indicate that there is a hormonal influence on the growth of the heterotransplanted tumours. These results provide further evidence for an influence of sex‐steroid hormones on the growth of glioblastomas.
Studies on the pathogenesis of neurological diseases associated with Varicella‐Zoster Virus
Authors: KENNEDY P. G. E. , BARRASS J. D. , GRAHAM D. I. , CLEMENTS G. B. 
Published: May 2008

Immunocytochemical techniques and in situ hybridization with three different Varicella‐Zoster Virus (VZV)‐specific RNA probes have been used to study the pathogenesis of VZV‐associated neurological syndromes. Varicella‐Zoster Virus antigens were not detected using the avidin‐biotin peroxidase technique with a polyvalent anti‐VZV antibody in any of the formalin‐fixed tissue sections from eight cases of VZV‐associated neurological disease (encephalitis, myelitis, ganglionitis); one case was immunosuppressed although inflammatory lesions were present. Intense labelling was detected within the inflammatory lesions in several representative VZV cases with a monoclonal antibody against Class II MHC antigens, whereas cases of Herpes Simplex Virus encephalitis and normal controls were not so labelled.Three VZV probes from open reading frames 62, 16 and 40, which show homology with the Herpes Simplex Virus immediate early 175 kd protein, the 65 kd DNA binding protein and the major capsid protein respectively, were used for in situ hybridization studies in these VZV tissues. Although the probes were able to detect VZV RNA in VZV‐infected CV‐1 and Flow 2002 cell cultures and formalin‐fixed VZV skin biopsy sections, positive hybridization was not seen in any of the neurological cases studied. Thus neither VZV nucleic acid nor antigens were detected in any of the cases of VZV‐associated neurological disease. It is proposed that the mechanism of neurological damage in the syndromes is immune‐mediated, there being increased expression of Class II MHC antigens associated with persistent inflammation.
The role of Schwann cells and basal lamina tubes in the regeneration of axons through long lengths of freeze‐killed nerve grafts
Authors: NADIM W. , ANDERSON P. N. , TURMAINE M. 
Published: May 2008

The ability of long acellular nerve grafts to support axonal regneration was examined using inbred rats. Grafts (40 mm long) of tibial/plantar nerves were used either as live grafts or after freeze‐drying to render the grafts acellular. The grafts were sutured to the proximal stump of severed tibial nerves in host animals which were then killed 1–12 weeks later. Axons rapidly regenerated through the living grafts but only extended 10–20 mm into the acellular grafts. This distance was achieved by 6 weeks and thereafter no significant further axonal extension occurred in the acellular grafts. A few naked axons lacking Schwann cell contact were identified in all acellular grafts, but became more numerous near the distal extent of axonal penetration into 6–12 week grafts. These axons contained large numbers of neurofilaments.When the distal 20 mm of 6 week acellular grafts (segments into which axons had not penetrated) were sutured to freshly severed tibial nerves, axons grew readily into the grafted tissue to a maximum distance of 9 mm. It is therefore likely that the limits to axonal regeneration through initially acellular grafts were set by factors intrinsic to the severed nerve. It is suggested that the limited migratory powers of Schwann cells may be one such factor. The concept that basal lamina tubes are not essential for axonal regeneration but may act as low resistance pathways for both axonal elongation and Schwann cell migration is discussed.
Aluminium maltol–induced neurocytoskeletal changes in fetal rabbit midbrain in matrix culture
Authors: HEWITT C. D. , HERMAN M. M. , LOPESM M. B. S. , SAVORY J. , WILLS M. R. 
Published: May 2008

We have developed a neuronal culture system to evaluate the neurotoxic effects of aluminium maltol on fetal rabbit midbrain sections containing the oculomotor nucleus. Cultures were treated with 5, 7, 9, 11, 13 and 15 μ.mol/1 aluminium maltol or 39 and 45 umol/1 maltol (molal equivalents to 13 and 15 umol/1 aluminium maltol). Control cultures were maintained in nutrient medium alone. Silver–positive neuritic swellings and occasional perikaryal neurofibrillary tangles were observed in cultures treated with 11, 13 and 15 umol/1 aluminium maltol. The number of tangles (involved neurons) produced in aluminium maltol treated cultures were counted and compared to (untreated) controls. We observed a total of 3, 7 and 7% of involved neurons following treatment with 11, 13 and 15 μmol/1 aluminium maltol respectively, and none in the control group. By immunohistochemistry, neurofibrillary tangles were immunoreactive with MAbs to phosphorylated (SMI–31), non–phosphorylated, phosphorylation dependent (SMI–32) and phosphorylation independent (SMI–33) epitopes of the high (–H) and middle (–M) molecular weight neurofilament subunits (NF–H/M). By contrast these lesions were nonreactive with MAbs recognizing tau, MAP2 or different β–tubulin isotypes. The perikaryal tangles consisted of focal accumulations of 10 nm straight filaments by electron microscopy.These findings are in agreement with previous data from rabbit in vivo studies after the administration of aluminium maltol intravenously (Bertholf et al, 1989) or intraventricularly (Katsetos et al, 1990). Using this in vitro system, aluminium–induced neurofibrillary tangles can be consistently produced, and changes in the distribution of neurofilament proteins evaluated. These studies may aid in the assessment of the possible role of aluminium in the aetiology of human neurodegenerative disorders.
Pituitary hyperplasia after goserelin (LHRH–analogue) therapy
Authors: RADNER H. , PUMMER K. , LAX S. , WANDSCHNEIDER G. , HÖFLER H. 
Published: May 2008

A 78–year–old male was treated with goserelin (Zoladex®) for 16 months for metastasizing prostate carcinoma. This therapy is clinically equivalent to orchidectomy, as the application of the luteinizing hormone–releasing hormone (LHRH)–analogue Zoladex® causes suppression of follicle–stimulating hormone (FSH) and luteinizing hormone (LH) by down–regulation of pituitary receptors. Consequently, testicular androgen production is inhibited and testosterone levels are decreased to castration levels.In the present case we found diffuse, partially nodular hyperplasia of growth hormone (GH) and adrenocorticotropin (ACTH) producing cells in the anterior pituitary gland at autopsy. As Zoladex® reduces pituitary receptors for releasing hormones (RH), a globally increased hypothalamic secretion of RH might be responsible for the ACTH– and the GH–cell hyperplasia. We cannot exclude that Zoladex® may cause not only adenomas in rat pituitary glands as Reported previously, but also a (nodular) hyperplasia of the pituitary gland in man.
Expression of alternative isoforms of the neural cell adhesion molecule (NCAM) on normal brain and a variety of brain tumours
Authors: FROST G. , PATEL K. , BOURNE S. , COAKHAM H. B. , KEMSHEAD J. T. 
Published: May 2008

A panel of monoclonal antibodies, including a reagent designated ERIC‐1, have been characterized as binding to the human neural cell adhesion molecule (NCAM). These monoclonal antibodies bind in a relatively uniform manner to a variety of normal and neoplastic tissues arising from the neuroectoderm. However, multiple forms of the protein are known to arise from the differential splicing of exons within the NCAM gene located on chromosome 11 at q23. On human adult brain, four isoforms of 180, 170, 145 and 120 kDa have been identified. Here, we Report the identification of another NCAM isoform of 95 kDa that is apparent on tissues following either N‐glycanase or neuraminidase treatment to remove carbohydrate and sialic acid residues from the molecule respectively.NCAM expression is further complicated by differential post‐translational modification of the molecule which is developmentally regulated. In general, fetal NCAM is more heavily polysialylated than the adult forms of the molecule. Human fetal brain has been shown to express the heavily sialylated embryonic form of NCAM, but following neuraminidase digestion, a similar pattern of NCAM expression is seen to that in adult brain. A variety of human brain tumours examined also show different patterns of NCAM expression, despite their uniform staining with monoclonal antibodies. The significance of these observations for designing new molecular and immunological approaches to the diagnosis of a variety of primary tumours is reviewed.
Vascular factors in the neurotoxic damage caused by 1, 3‐dinitrobenzene in the rat
Authors: ROMERO I. , BROWN A. W. , CAVANAGH J. B. , NOLAN C. C. , RAY D. E. , SEVILLE M. P. 
Published: May 2008

Using a 3 times 10 mg/kg dose schedule of 1, 3‐dinitrobenzene (DNB) over two days in Fischer rats, we have found the following changes in vascular function and structure during the early phase of the symmetrical brain stem lesions.1 Marked increase in cerebral blood flow generally but especially in the inferior colliculi, from 6 h after the final dose of DNB.2 Increasing incidence of petechial haemorrhages in inferior colliculi, cerebellar roof, vestibular and superior olivary nuclei from 12 h.3 Focal leakage of horseradish peroxidase and many sleeve‐like arteriolar haemorrhages seen in vibratome sections and by scanning electron microscopy (SEM) in these regions from 12 h.4 Periarteriolar oedema and protein leakage present in step‐serial sections in these regions from 12 h, with astrocyte swelling and occasional small infarcts.These changes suggest that the vascular bed may play an important role in the pathogenesis of these lesions, perhaps in parallel with early astroglial damage. They are discussed in relation to (i) the known presence of xanthine oxidase in the vascular bed of the brain and the likelihood of ‘useless redox cycling’ with free radical generation from this enzyme's interaction with nitroheterocyclic compounds, and (ii) the possible role of free radical damage to endothelial cells in this intoxication and in the analogous lesions of natural and experimental Wernicke's encephalopathy.
Ubiquitin, PGP 9.5 and dense body formation in trimethyltin intoxication: differential neuronal responses to chemically induced cell damage
Authors: ANDERSON V. E. R. , HAJIMOHAMMADREZA I. , GALLO J. M. , ANDERTON B. H. , UNEY J. , BROWN A. W. , NOLAN C. C. , CAVANAGH J. B. , LEIGH P. N. 
Published: May 2008

Ubiquitin in normal cells may be important in degrading or transferring short‐lived or aberrant proteins to lysosomal dense bodies. To examine its role in degrading proteins produced by a chemical insult, changes in the distribution of ubiquitin and the carboxy‐terminal hydrolase, PGP 9.5, have been studied in rat hippocampal neurons and cerebellar Purkinje cells in trimethyltin intoxication. Here tubulovesicular dense bodies (TVBs) form from 12 h onwards associated with vacuolation of the Golgi apparatus. Striking accumulations of lysosomal dense bodies follow in hippocampal pyramidal cells but not in cerebellar Purkinje cells; many of the hippocampal neurons later die, while the Purkinje cells generally survive.Ubiquitin immunoreactivity was diffusely increased in hippocampal pyramidal and Purkinje cells 6h after dosing. By 12 h both diffuse and granular ubiquitin immunoreactivity was present that intensified over 24 and 48 h. Both by light and electron microscopy TVBs showed ubiquitin immunoreactivity, but dense bodies in hippocampal perikarya did not stain with an anti‐ubiquitin antibody. PGP 9.5 immunoreactivity was not altered in hippocampal cells at any time, while Purkinje and Golgi cell dendrites and perikarya showed intensified labelling at 3 h that reached a peak of 12 h. At 48 h Western blot analysis of hippocampal homogenates showed significant increases in high molecular weight (HMW) ubiquitin conjugates, while cerebellar homogenates showed an increase in ubiquitin‐histone conjugates. Northern blot analyses showed no change in ubiquitin or PGP 9.5 gene expression in hippocampus or cerebellum. These findings suggest that the material in the TVBs in hippocampal cells is not being degraded by the ubiquitin system but passes unubiquitinated into the lysosomal system, while material in Purkinje cell TVBs is degraded by the ubiquitin system, suggesting it may have a different composition in each type of neuron.
Parvalbumin and calbindin D‐28k in the human motor system and in motor neuron disease
Authors: Ince P. , Stout N. , Shaw P. , Slade J. , Hunziker W. , Heizmann C.W. , Baimbridge K.G. 
Published: May 2008

Calbindin D‐28k and parvalbumin are neuronal calcium binding proteins of interest in relation to neurodegenerative diseases. Expression of calbindin and parvalbumin may be one of the determinants of selective vulnerability in these disorders. The distribution of these proteins was surveyed in the normal human motor system and in motor neuron disease (MND) using immunocytochemistry in formalin fixed post‐mortem tissues. CNS tissues from 14 MND patients (mean age 61.2 years, mean post‐mortem delay 24.6 h) and seven controls (mean age 62.6 years, mean post‐mortem delay 25.3 h) were studied. Preliminary studies on the effects of fixation were performed. In normal cases upper and lower motor neurons showed absent expression of both proteins.Several neuronal groups characteristically spared in MND showed varying patterns of immunoreactivity: oculomotor neurons showed parvalbumin staining of the perikaryon; the thoracic preganglionic sympathetic neurons showed calbindin staining in perikarya, Onuf's nucleus showed calbindin staining in the neuropil only. In motor neuron disease a loss of ventral horn interneurons and calbindin immunoreactive processes was observed with no other disease related changes in the spinal cord, brainstem, or motor cortex. These findings are consistent with the hypothesis that the distribution of these proteins is one determinant of selective vulnerability to the neurodegenerative processes in MND acting via disturbance of neuronal calcium homeostasis.
Partial reversal of aluminium‐induced neurofibrillary degeneration by desferrioxamine in adult male rabbits
Authors: Savory J. , Herman M. M. , Erasmus R. T. , Boyd J. C. , Wills M. R. 
Published: May 2008

J. Savory, M. M. Herman, R. T. Erasmus, J. C. Boyd and M. R. Wills (1994) Neuropathology and Applied Neurobiology 20, 31–37Partial reversal of aluminium–induced neurofibrillary degeneration by desferrioxamine in adult male rabbitsDesferrioxamine, a chelating agent with a high affinity for aluminium, has been reported to slow the clinical progression of dementia associated with Alzheimer's disease [4], We report here the effects of desferrioxamine treatment on aluminium–induced neurofibrillary degeneration in rabbits. Adult male New Zealand white rabbits received a single injection of aluminium–maltolate into the lateral cerebral ventricle. Three days later, one group of rabbits was treated with intramuscular injections of desferrioxamine twice daily; a second group received saline instead of desferrioxamine. Both groups were sacrificed 4 or 5 days following initiation of desferrioxamine or saline treatment. Minimal neurofibrillary degeneration was found in two of six desferrioxamine–treated rabbits, while all six rabbits treated with saline showed extensive neurofibrillary degeneration, particularly in the ventral horn of the lower spinal cord. Quantitation of the neurofibrillary degeneration in ventral horn neurons of lumbar cord revealed 30% to be affected in saline–treated animals compared to zero affected neurons following desferrioxamine treatment. When sacrificed just 3 days after aluminium treatment, 50% of the rabbits already revealed neurofibrillary degeneration, corresponding to the timepoint when desferrioxamine treatment was begun in the above animals; on quantitation, 7.5% of ventral lumbar cord neurons were involved. These findings indicate a partial reversal of aluminium–induced neurodegeneration by desferrioxamine. Delaying desferrioxamine treatment to 6 days after aluminium administration prevented any reversal of the aluminium effect; all animals had abundant neurofibrillary degeneration as well as a striking basophilic spicular deposit of calcium and argyrophilic material in the leptomeninges, lateral ventricles and brain parenchyma adjacent to these areas. Pre–treatment of rabbits with desferrioxamine did not provide the expected protective effect against aluminium–induced neurofibrillary degeneration. No pathological effects were observed when saline or desferrioxamine were given alone, without aluminium