bluuebunny/crossref_metadata_2025 huggingface dataset:
INHERITED PRENATAL HYDROCEPHALUS IN THE H–Tx RAT: A MORPHOLOGICAL STUDY
Authors: JONES H. C. , BUCKNALL R. M.
Published: May 2008

Inherited prenatal hydrocephalus in the H–Tx rat: a morphological study

The H–Tx rat has inherited hydrocephalus which is present at birth. In order to investigate the onset and early stages of hydrocephalus, the heads of fetuses from 16 to 21 days gestation and at 1 day after birth, were serially sectioned using conventional wax histology. Lateral and third ventricle volumes were measured with a graphics tablet and microcomputer. Hydrocephalus was first detected at 18–20 days gestation by enlarged lateral ventricles and it was sometimes accompanied by a large third ventricle. Most hydrocephalics had a non–patent cerebral aqueduct between the third ventricle and the posterior collicular recess and the remainder (about 25%) had an aqueduct which was patent but with a smaller lumen than in non–hydrocephalic littermates. Some fetuses prior to 18 days gestation with normal lateral ventricles also had nonpatent aqueducts. Abnormal aqueducts were lined by ependymal cells which were ventrally displaced by thickening of the overlying midbrain; also the subcommissural organ was foreshortened. Infusion with fluorescent markers confirmed that the flow pathway through the aqueduct was obstructed in many hydrocephalic rats. It is concluded that the hydrocephalus may be the result of abnormal brain development in the midline region of the dorsal mesencephalon, leading to aqueduct closure.
PERSISTENT MERCURY IN NERVE CELLS 16 YEARS AFTER METALLIC MERCURY POISONING
Authors: HARGREAVES R. J. , EVANS J. G. , JANOTA I. , MAGOS L. , CAVANAGH J. B.
Published: May 2008

Hargreaves R.J., Evans J. G., Janota I., Magos L. & Cavanagh J. B. (1988) Neuropathology and Applied Neurobiology 14, 443–452

Persistent mercury in nerve cells 16 years after metallic mercury poisoning

A male subject, after exposure to mercury metal at work in 1968, developed classical signs of mercurialism from which he made a slow clinical recovery. He subsequently developed psychoneurotic symptoms and became an alcoholic; he never returned to work and died in 1984. No histological changes relevant to mercury intoxication were found in the brain, but staining by Danscher & Schroeder's method for mercury showed many positively staining lysosomal dense bodies in a large proportion of nerve cells, and the presence of mercury was confirmed by elemental X–ray analysis. The mercury content of the brain was increased, much of it being present in colloidal form.
VARICOSITIES IN HUMAN FETAL SCIATIC NERVE FIBRES
Authors: TOMÉ F. M. S. , TEGNÉR R. , CHEVALLAY M.
Published: May 2008

Tome F. M. S., Tegner R. & Chevallay M. (1988) Neuropathology and Applied Neurobiology 14, 495–504

Varicosities in human fetal sciatic nerve fibres

A morphological study performed on sciatic nerves from 10 fetuses aged 19 to 32 weeks revealed variations in axonal diameter along the length of the fibres but a uniform myelin sheath thickness. This gave the fibres a beaded appearance. The diameter of the axon in the varicosities was up to seven–times greater than that of the intervening axon. The varicosities were separated by distances up to 50 μm. Both myelinated and single unmyelinated fibres had varicosities. Neurofilaments and neurotubules were more densely packed in the axons between the varicosities. The absolute number of filaments and tubules per axon was similar in axons with equal numbers of myelin lamellae but with different diameters, as calculated from transverse sections. The varicosities were observed in all fetuses aged 19 to 24 weeks, but in only one of the two fetuses aged 28 weeks. They were not present in the 32 week fetus. They appear to be a characteristic morphological feature of nerve fibres during early fetal life and can be identified only in teased fibre preparations or in longitudinal sections of the nerve. Their presence explains the bimodal or markedly skewed distribution of myelinated fibre axon diameters that was seen in nerves from young fetuses. It also helps in understanding the discrepancies reported in size patterns between axon diameter and myelin thickness. It is possible that the varicosities may be partially artefactual but their occurrence may imply a particular vulnerability of fetal nerve fibres. Their production may be related to movements of the axoplasmic fluid which is abundant in young fetuses.
INCREASED DIAMETER OF DEMYELINATED AXONS IN CHRONIC MULTIPLE SCLEROSIS OF THE SPINAL CORD
Authors: SHINTAKU M. , HIRANO A. , LLENA J. F.
Published: May 2008

Shintaku M., Hirano A. & Llena J. F. (1988) Neuropathology and Applied Neurobiology 14, 505–510

Increased diameter of demyelinated axons in chronic multiple sclerosis of the spinal cord

In an autopsied case of chronic multiple sclerosis, many axons in some demyelinated plaques of the spinal cord had remarkably increased diameters and reduced argentophilia. The increase in axonal diameter extended for some distance and was restricted to the demyelinated areas. A review of 22 autopsy cases of chronic multiple sclerosis revealed similar findings in the plaques of the spinal cord in seven cases. They were also noted in the brain but much less frequently. On electron microscopy, the neurofilaments in these enlarged demyelinated axons were not closely packed but were separated by an increased amount of electron–lucent axoplasm. It is thought that this finding may be a manifestation of increased water content in the axoplasm secondary to increased permeability of the demyelinated axolemma.
ROSENTHAL FIBRES ARE BASED ON THE UBIQUITINATION OF GLIAL FILAMENTS
Authors: LOWE J. , MORRELL K. , LENNOX G. , LANDON M. , MAYER R. J.
Published: May 2008

Rosenthal fibres are based on the ubiquitination of glial filaments

Immunocytochemical localization of the cell stress‐associated protein ubiquitin was performed on human lesions containing Rosenthal fibres. Ubiquitin was localized around the periphery of classical Rosenthal fibres but not in the amorphous central areas; the ubiquitin‐positive regions corresponded to the immunocytochemical localization of glial fibrillary acidic protein (GFAP). Compact bundles of GFAP in glial processes without a non‐staining core were also associated with ubiquitin, while loosely aggregated cellular GFAP was not. The relationship between compact bundles of GFAP and the amorphous osmiophilic central component of Rosenthal fibres has been uncertain. These data, however, show that the compact bundles of glial filaments are distinct from normal GFAP in being associated with ubiquitin. A role for ubiquitin in Rosenthal fibre formation is suggested. We propose that the term Rosenthal fibre be restricted to mean the hyaline amorphous core of these structures, while realizing that this is based on a wider abnormality of surrounding glial fibrillary acidic protein filaments.
THE CORRELATION OF ELECTRORETINOGRAPHIC AND HISTOPATHOLOGICAL FINDINGS IN THE EYES OF MICE INFECTED WITH THE 79A STRAIN OF SCRAPIE
Authors: CURTIS R. , FRASER H. , FOSTER J. D. , SCOTT J. R.
Published: May 2008

The correlation of electroretinographic and histopathological findings in the eyes of mice infected with the 79A strain of scrapie

Retinal degeneration was produced using the 79A strain of scrapie injected intracerebrally into mice of the MM inbred strain, and studied by electroretinography and light and electron microscopy during the preclinical and clinical phases of the disease. The changes in the electroretinogram (ERG), detectable in some mice at 118 days postinjection (d.p.i.), appeared to coincide with the earliest morphological evidence of photoreceptor damage. In the early stages there was a progressive reduction of b‐wave amplitude without marked loss of retinal sensitivity or significant change in a‐ and b‐wave peak implicit times. Extinction of the ERG, observed in half the mice examined at 144 d.p.i., approximated to a stage of the retinopathy in which the outer nuclear layer was reduced to about four rows of nuclei. Early morphological changes suggested that the primary lesion involved the integrity of the photoreceptor as a whole, the electrophysiological findings reflecting a primary loss of light sensitive tissue rather than impairment of the transduction mechanism or neurotransmission.
REPORTS OF MEETINGS
Authors: LUTHERT P. , PILKINGTON G. J.
Published: May 2008

BLOOD–BRAIN BARRIER CLUB: FOURTH ANNUAL SYMPOSIUM, INSTITUTE OF PSYCHIATRY, LONDON 27 APRIL (1988)

THE BRITISH GLIOMA GROUP: EIGHTH ANNUAL MEETING, UNIVERSITY OF SURREY, GUILDFORD 2728 JULY 1988
EXPERIMENTAL MURINE HERPES SIMPLEX ENCEPHALITIS: IMMUNOHISTOCHEMICAL DETECTION OF VIRUS ANTIGENS
Authors: WEBB S. J. , EGLIN R. P. , READING M. , ESIRI M. M.
Published: May 2008

Inbred Balb/c female mice were intranasally inoculated with 1 μd of a suspension of herpes simplex virus type 1 adjusted to contain the required infectivity. Doses of virus inoculated ranged from 1 × 102 plaque forming units (p.f.u.) to 1 × 106 p.f.u. Humoral and cellular immunological response of the animals was studied for the acute phase of the disease, defined as being up to 14 days post infection. Localization of virus–antigen positive cells, detected by immunoperoxidase staining, was monitored daily for the acute phase. Immune responses directly reflected virus input, with the highest response to 1 × 106 p.f.u. of herpes simplex virus. The neuro–anatomical localization of virus–antigen positive cells was found mainly in the hippocampus and entorhinal cortex for inoculum doses of 1 × 106 p.f.u. and mainly in the brain stem for inoculum doses 5 × 102 p.f.u. The lower–mortality rate of animals inoculated with 5 × 102 p.f.u. has identified this dose as suitable for use in the study of sites of latency within the central nervous system and in the investigation of reactivation of herpes simplex virus type 1 in causing encephalitis.
FIBRE DISORGANIZATION IN THE NEOCORTEX OF PATIENTS WITH SENILE DEMENTIA OF THE ALZHEIMER TYPE
Authors: DUYCKAERTS C. , KAWASAKI H. , DELAERE P. , RAINSARD C. , HAUW J. J.
Published: May 2008

The loss of neurons, which is thought to occur during senile dementia of the Alzheimer type, could alter the fibre organization of the neocortex. In the present study, the density and course of the fibres were measured in histological sections in 14 cases: all were women over 75 years of age who had been living in a long–stay hospital and had been prospectively assessed by the test score of Blessed et al. (1968). Their intellectual status ranged from nearly normal to severely demented. Samples from the supramarginal and prefrontal gyri were studied after Bodian's impregnation. The course of the fibres in 3–dimensional space was determined by two angles: (a) the angle which characterized their orientation in the plane of section and discriminated between horizontal (tangential), vertical (radial) and oblique fibres and (b) the angle of section with which the fibres were cut. The total density of fibres correlated neither with the test score nor with the density of neurofibrillary tangles or senile plaques. The percentage of obliquely orientated fibres and of fibres with a high sectioning angle increased in the course of the disease. This increase was mainly at the expense of the horizontal fibres in the supramarginal gyrus and could be explained by the presence of a great number of small, tortuous and abnormally orientated fibres (kinked fibres) in the most severely affected cases. The methodology employed in this study could be useful in the investigation of fibre architecture in other diseases involving the cerebral cortex.
IMMUNOCYTOCHEMICAL CHARACTERIZATION OF THE MACROPHAGE AND LYMPHOCYTE INFILTRATE IN THE BRAIN IN SIX CASES OF HUMAN ENCEPHALITIS OF VARIED AETIOLOGY
Authors: ESIRI M. M. , READING M. C. , SQUIER M. V. , HUGHES J. T.
Published: May 2008

Monoclonal antibodies that react with various macrophage and lymphocyte sub–populations have been applied to acetone–fixed cryostat sections of brains from six cases of human meningo–encephalitis (two cases of subacute sclerosing panencephalitis, two cases of allergic encephalitis, one case of suspected entero–virus meningo–encephalitis and one case of meningo–encephalitis of undetermined origin). The patterns of inflammatory cell response that these antibodies reveal is described and discussed in comparison with published descriptions of the corresponding cell types found in the brain in Japanese encephalitis, herpes simplex encephalitis and multiple sclerosis. In general, in the acute phases of inflammatory central nervous system diseases, T lymphocytes and macrophages predominate in the parenchyma, while the early phases of a B cell response take place in perivascular spaces.
INTRANEURONAL EOSINOPHILIC BODIES OF BEEF CATTLE (JAPANESE BROWN)
Authors: FUKUDA T. , KISHIKAWA M.
Published: May 2008

Eosinophilic cytoplasmic inclusion bodies were observed in the midbrain, pons, medulla and spinal cord of beef cattle (Japanese Brown). The inclusion bodies, observed in 14 of 20 cases exhibiting neurological signs and in one of nine healthy cases, differed in morphology and/or staining properties from previously reported inclusion bodies in humans and animals.
CEROID–LIPOFUSCINOSIS (BATTEN'S DISEASE): PATHOGENESIS AND SEQUENTIAL NEUROPATHOLOGICAL CHANGES IN THE OVINE MODEL
Authors: JOLLY R. D. , SHIMADA A. , DOPFMER I. , SLACK P. M. , BIRTLES M. J. , PALMER D. N.
Published: May 2008

A sequential morphological study of ovine ceroid–lipofuscinosis showed that brains of affected lambs were normal at birth, grew until four months of age but then atrophied. Laminar necrosis of cerebral cortex was noted at 10 weeks, occurring first in the parietal area, then spreading to involve frontal and occipital areas while the temporal lobe was least and last affected. With progression of the disease, the laminar pattern was lost. Neuronal necrosis was accompanied by a severe astrocytosis. The granular and multilamellar storage cytosomes increased in size with age. Their structure was interpreted as paracrystalline in which repeating molecules of the dominantly stored lipid binding subunit of mitochondrial ATP synthase interact with neutral lipids and phospholipids. Abnormal cytosomes in neurons of lamb fetuses and a neonate were interpreted as early lesions which contained whorls or stacks of bilayered membrane as well as the more complex multilamellar material. The underlying anomaly leading to the storage of the lipid binding subunit of mitochondrial ATPsynthase remains to be defined. However, it is noted that this disease should be regarded as a lipid binding protein proteinosis or alternatively as a proteolipid proteinosis.
AN IMMUNOHISTOCHEMICAL CHARACTERIZATION OF THE PRIMITIVE AND MATURING NEUROEPITHELIAL COMPONENTS IN THE OTT–6050 TRANSPLANTABLE MOUSE TERATOMA
Authors: CACCAMO D. V. , KATSETOS C. D. , FRANKFURTER A. , COLLINS V. P. , VANDENBURG S. R. , HERMAN M. M.
Published: May 2008

The neuroepithelial component of the OTT–6050 mouse teratoma has previously been characterized as an experimental system for the study of differentiation and cytologic maturation in embryonal tumours of the human central nervous system. A number of transplantable tumours composed of primitive stem cells and of a neuroepithelial component displaying a spectrum of differentiation were previously produced by centrifugal elutriation of the dissociated OTT–6050 teratoma. These tumours have provided a reproducible cell population that has permitted the study of both the early and later stages of neoplastic neurocytogenesis.

The purpose of the present study was to detect, by immunohistochemistry, the earliest stages of neurocytogenesis in these tumours as shown by the expression of neuron–associated microtubule proteins. This was correlated to the appearance and localization of other markers associated with neuronal and glial differentiation. The primitive neuroepithelial structures resembling neural tubes (medulloepithelial rosettes) contained single or small groups of cells which reacted with the monoclonal antibody TUJl, specific for the neuron–associated class III β–tubulin isotype. Immature neuroblasts and maturing polar neurons also showed immunoreactivity with TUJl, whereas reactivity for microtubule–associated protein 2 (MAP2), tau, the 200 kilodalton isoform of neurofilament protein, neuron–specific enolase and synaptophysin was primarily seen in maturing neurons. By comparison, both medulloepithelial and ependymoblastic rosettes, neuroblasts and glial cells were immunopositive with monoclonal antibody TU27, which defines an antigenic site shared by most mammalian β–tubulin isotypes. Astroglia were reactive with antisera to glial fibrillary acidic and S–100 proteins, but not with monoclonal antibody (MAb) TUJ1, or with MAbs to the other neuron–associated cytoskeletal proteins, MAP2, tau and the 200 kilodalton subunit of neurofilament protein.

Our findings suggest that (1) expression of the class III β–tubulin isotype is an early event during neoplastic neurocytogenesis, (2) this isotype is subsequently preserved in maturing neuronal populations, and (3) it is not present at detectable levels in stem cells or glial cells. The observation that morphologically undifferentiated neuroepithelial cells express a neuron–associated β–tubulin isotype signifies the value of examining tubulin isotype expression in the characterization of normal and neoplastic neuroepithelial differentiation.
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.
SPONTANEOUS RECOVERY FROM THE ENCEPHALOMYELITIS IN MICE CAUSED BY STREET RABIES VIRUS
Authors: JACKSON A. C. , REIMER D. L. , LUDWIN S. K.
Published: May 2008

Recovery from rabies was studied in an experimental model. Young adult mice were inoculated in a hindlimb footpad with street rabies virus (fox salivary gland isolate). In a group of 62 mice, 97% developed clinical rabies with paresis of the extremities and spasticity, and 37% recovered with neurological sequelae. There was an acute inflammatory reaction in the brainstem and grey matter of the spinal cord, and degeneration of myelinated axons in the white matter of the cord and in the dorsal roots. Rabies virus antigen was found in the central nervous system of all mice examined between day 5 and 13, and also in trigeminal and dorsal root ganglia. Surviving mice had neutralizing antibodies in serum and brain tissue, and 90% survived an intracerebral challenge with the CVS strain of fixed rabies virus. Spontaneous recovery from rabies encephalomyelitis was demonstrated with evidence of viral replication and pathological changes in the central nervous system.
REGENERATION IN THE PERIPHERAL NERVOUS SYSTEM
Authors: HALL SUSAN M.
Published: May 2008

Mammalian peripheral nerve fibres can regenerate after injury. Repair is most likely to succeed if axons are simply crushed or have only a very short (< 0–5 cm) interstump gap to cross and most likely to fail if the interstump gap is long (> l cm) and associated with soft tissue damage. Whereas reactive axonal sprouting appears to be an intrinsic neuronal response to injury, the subsequent organization of the axonal sprouts, in particular their orderly outgrowth in minifascicles towards a distant distal stump does not occur unless Schwann cells are present. During the injury response, Schwann cells proliferate; co–migrate with regrowing axons (when the proximal stump is separated from the distal stump); respond to axonal cues by transient upregulation or re–expression of molecules which provide a favourable substrate for axonal extension; and attract bundles of regrowing axons and their associated Schwann cells across interstump gaps up to 1 cm in length. Recruited macrophages remove myelin debris from the Schwann cell tubes; they probably interact with Schwann cells in other ways during the injury response, e.g. by presenting mitogens and cytokines.
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.
Cell proliferation patterns in the diagnosis of astrocytomas, anaplastic astrocytomas and glioblastoma multiforme: a Ki‐67 study
Authors: RAGHAVAN R. , STEART P. V. , WELLER R. O.
Published: May 2008

Although astrocytomas, anaplastic astrocytomas and glioblastoma multiforme differ in their clinical courses, histological distinction between these three tumours and between astrocytomas and anaplastic astrocytomas in particular may be unclear on histology alone especially in small biopsies. In the present study, a more objective way of distinguishing between the three types of tumour is sought. Frozen sections from 26 astrocytomas, 26 anaplastic astrocytomas and 38 glioblastomas were stained by an indirect immunoperoxidase technique using the monoclonal antibody Ki‐67 which binds to nuclear proteins in the G1, S, G2 and M phases of the cell cycle. The Ki‐67 staining was assessed quantitatively through direct observation of the stained sections by the use of a drawing tube attached to a microscope. A minimum of 1000 cells was counted in each case and labelled cells were expressed as a percentage of the total number of cells. These results, when correlated in each case with the histology of the tumour in paraffin sections, showed Ki‐67 labelling indices ranging from 0 to 1.9% (mean 0.5% SD±0.54) in astrocytomas, 0.6 to 10.9% (mean 4.1% SD±2.8) in anaplastic astrocytomas and 0.9 to 16.2% (mean 6.4% SD±3.34) in glioblastoma multiforme. The differences in the three types of tumour were statistically significant. The results suggest that Ki‐67 staining is a useful addition to the panel of techniques for distinguishing between astrocytomas, anaplastic astrocytomas and glioblastoma multiforme.
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.
Inclusion body myositis in French patients. A clinicopathological evaluation
Authors: MHIRI C. , GHERARDI R.
Published: May 2008

In order to establish the frequency of inclusion body myositis (IBM) in a European neuropathological unit and to evaluate the specificity of IBM pathology, we reviewed the 850 muscle biopsies performed in our laboratory over the past 7 years. Clinical histopathological and ultrastructural evaluation of all cases showing rimmed vacuoles, a constant histopathological feature of IBM, was done and the diagnosis of IBM was assessed using the clinico‐pathological criteria of Calabrese, Mitsumoto & Chou (1987). Among the nine cases showing rimmed vacuoles, five were classified as IBM (group 1), either definite (3/5) or probable (2/5), and four suffered from a chronic denervating process of muscle (group 2). The overall frequency of IBM (06% of all muscle biopsies) was similar to that reported by North American authors. IBM represented 16% of adult idiopathic inflammatory myopathies investigated in our laboratory. Clinical and histopathological findings in group 1 were homogeneous and distinctive. Muscle biospy was consistent with an inflammatory myopathy in all patients in group 1 and with a non‐inflammatory denervating process in 3/4 patients in group 2. Typical intrasarcoplasmic inclusions were detected by electron microscopy in 3/5 cases in group 1 and 1/4 in group 2, which raises questions about the specificity of the 16 18 nm tubulofilaments. Failure to demonstrate inclusions in two patients with otherwise typical IBM, was probably related to the paucity of rimmed vacuoles observed in these cases.
Segregation of viral structural proteins in cultured neurons of rat spinal ganglia and cord
Authors: WECLEWICZ K. , KRISTENSSON K. , ÖRVELLM C.
Published: May 2008

Cultured spinal ganglion and spinal cord neurons were used to examine the intraneuronal distribution of five structural proteins of Sendai virus by immunohistochemistry. In spinal ganglion cells the internal, cytosolic viral proteins (the nucleocapsid, polymerase and matrix proteins) were confined to the perikarya, while the envelope glycoproteins (the haemagglutinin‐neuraminidase and fusion proteins) also appeared in the axon‐like processes. All five proteins occurred in the dendrite‐like processes of spinal cord neurons. In both types of neuron the cytosolic viral proteins showed a pattern of distribution similar to that observed for the microtubule‐associated protein MAP2. The segregated occurrence of the viral envelope and cytosolic proteins in axons may prevent virus assembly in axons and limit long‐distance spread of paramyxoviruses in the nervous system.
Immunohistochemical evidence for the selective involvement of dorsal root fibres in Friedreich's ataxia
Authors: GOTO S. , HIRANO A.
Published: May 2008

An immunohistochemical study was carried out in order to elucidate the selective involvement of the dorsal root fibres from two patients with Friedreich's ataxia in comparison with those of 10 neurologically normal control individuals. For this purpose, antibodies to substance P and to synaptophysin were used. Substance P‐immunoreactive unmyelinated fibres forming a dense network in the normal substantia gelatinosa of the spinal dorsal horn predominantly originate from a subpopulation of small cells of the dorsal root ganglia, while synaptophysin is present in virtually all nerve cell axon terminals and is useful for visualizing axon terminals in the nervous system. Strong substance P‐like immunoreactivity was seen in the substantia gelatinosa of patients with Friedreich's ataxia. By contrast, there was marked depletion of synaptophysin immunoreactivity in the posterior column nuclei, with the gracile nucleus showing greater loss of positive puncta than the cuneate nucleus.
Monocyte‐mediated entry of pathogens into the central nervous system
Authors: WILLIAMS A. E. , BLAKEMORE W. F.
Published: May 2008

The origin of the microglia has long been a subject of debate. However it is now clear that monocytes enter the normal central nervous system and follow a series of morphological transformations as they differentiate into microglia. Thus, microglia are of monocytic origin. Since monocytes migrate into the normal CNS, they represent potential vehicles for the entry of pathogens into the nervous system and indeed may carry particulate matter into the CNS. Both viruses and bacteria use this ‘Trojan horse’ mechanism of entry in the pathogenesis of CNS disease.
Presence of inclusion body myositis‐like filaments in oculopharyngeal muscular dystrophy. Ultrastructural study of 10 cases
Authors: COQUET M. , VITAL C. , JULIEN J.
Published: May 2008

Ten cases of oculopharyngeal muscular dystrophy (OPMD) were examined ultrastructurally. Two very different types of filamentous inclusions were observed: (1) Nuclear inclusions composed of 8.5 nm external diameter tubular filaments organized in palisades and similar to those described by Tomé and Fardeau (1980). They have not yet been reported in other muscle diseases. Their presence in 100% of our cases confirms they are the morphological hallmark of OPMD. (2) 16–18 nm external diameter tubular filaments. These were similar to the inclusions observed in inclusion body myositis (IBM) and morphologically very different from the first type. They were randomly dispersed or arranged in bundles near cytoplasmic debris and whorls of membranes. They were found in cytoplasm. Only once were they observed in a nucleus. These inclusions have been described in IBM but also in other diseases. They were found in 80% of our OPMD cases.
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.
Nucleolar organizer regions and post–operative survival in glioblastoma multiforme
Authors: NICOLL J. A. R. , CANDY E.
Published: May 2008

Counts of argyrophil nucleolar organizer regions (AgNORs) have been proposed as a method of assessing tumour growth rate. AgNOR counts have been shown to correlate with histological grade in glial and some non–glial tumours but few studies have included data relating to clinical outcome. We have examined the relationship between tumour AgNOR counts and postoperative survival in a retrospective study of 54 patients with glioblastoma multiforme. The mean number of AgNORs per nucleus varied from 1.7 to 10.8 in biopsies from different patients and correlated with mitotic rate (P < 0.01) but not with post–operative survival, which ranged from 2 days to 54 months with four patients still alive. AgNOR counts were inversely related to patient age (P < 0.01) and older patients tended to survive for shorter periods (P < 0.05). Although AgNOR counts are related to the rate of tumour cell division, they are not useful for predicting the post–operative survival of patients with glioblastoma multiforme.
Ubiquitin and heat shock protein expression in amyotrophic lateral sclerosis
Authors: GAROFALO O. , KENNEDY P. G. E. , SWASH M. , MARTIN J. E. , LUTHERT P. , ANDERTON B. H. , LEIGH P. N.
Published: May 2008

The expression of two heat shock proteins, HSP72 and p57, in addition to ubiquitin, has been studied immunocytochemically in nine amyotrophic lateral sclerosis (ALS) cases and 10 agematched controls. HSP72 and p57 antibodies did not identify the characteristic ubiquitinimmunoreactive inclusions present in anterior horn cells in ALS spinal cord. Antibodies to HSP72, but not to p57 or ubiquitin, strongly labelled structures corresponding to polyglucosan bodies in spinal grey matter. Such immunoreactive profiles were more abundant in ALS cases, although they were also present in control material. They were sometimes identified by haematoxylin and eosin and periodic acid Schiff reaction, but were not labelled by phosphotungstic acid haematoxylin or by antibodies to glial fibrillary acidic protein. Although ubiquitin, HSP72 and p57 are stress–induced proteins, they are expressed differently and might therefore have different significance in neuronal degeneration.
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.
Heat shock in cultured neurons and astrocytes: correlation of ultrastructure and heat shock protein synthesis
Authors: NISHIMURA R. N. , DWYER B. E. , VINTERS H. V. , DE VELLIS J. , COLE R.
Published: May 2008

Cultured cerebral cortical neurons and astrocytes were compared after a brief heat shock. Morphological findings were correlated with the synthesis of the 68 kD heat shock protein (HSP68). Heat shocked neurons demonstrated many severe morphological changes after exposure to temperatures of 43°C for 15 min and 45°C for 10 min. Nuclear membrane ‘blebbing’ with lysis of the membrane, chromatin clumping, and disappearance of the nucleolus were prominent after both conditions. Lysis of the cell membrane was noted in severely injured neurons; this was more prominent at the higher temperature. In addition, alterations to polyribosomes, Golgi apparatus, rough endoplasmic reticulum and mitochondria were noted in the cytoplasm of neurons after heat shock. In contrast, no significant changes were noted in either the nucleus or cytoplasm of heat shocked astrocytes. The severity of morphological changes in neurons directly correlated with the low level of induction of HSP68 in neurons. Neurons synthesized much less 68 kD heat shock protein than similarly heat shocked astrocytes. We conclude that cultured cerebral cortical neurons are more susceptible to injury after heat shock than heat resistant astrocytes and that one possible mechanism of injury is failure to synthesize adequate amounts of HSP68 after injury.
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.
Autopsy neuropathological findings in ‘burnt out’ herpes simplex encephalitis and use of the polymerase chain reaction to detect viral DNA
Authors: NICOLL J. A. R. , MAITLAND N. J. , LOVE S.
Published: May 2008

We have conducted an autopsy study of the brains of three patients with ‘burnt out’ temporal and frontal lobe encephalitis, thought to be due to previous herpes simplex virus infection. The brains showed marked atrophy and yellow‐brown discolouration predominantly involving the anterior part of both temporal lobes. Histology revealed destruction of grey and white matter, perivascular and leptomeningeal aggregates of lymphocytes and macrophages, and severe gliosis. Immunohistochemistry for herpesvirus antigens was negative but, by use of the polymerase chain reaction, a segment of the thymidine kinase gene of herpes simplex virus type 1 was detected in sections of temporal lobe from all three brains. These findings support the hypothesis that herpes simplex virus may persist within the central nervous system after acute herpes encephalitis, to cause latent or low‐grade productive infection.