bluuebunny/crossref_metadata_2025 huggingface dataset:
PATHOLOGICAL BASIS FOR NEUROTRANSMITTER CHANGES IN PARKINSON'S DISEASE
Authors: MANN D. M. A. , YATES P. O.
Published: May 2008

In eight patients with idiopathic Parkinson's disease, loss of nerve cells from the locus caeruleus, together with reductions in capacity for function in those of the dorsal motor vagus nucleus, the supraoptic and paraventricular nuclei of the hypothalamus and the nucleus basalis of Meynert in the substantia innominata are reported. These changes were more severe in three of these eight patients where mental impairment was present, though in none of these three was the number of senile plaques and neurofibrillary tangles or extent of granulovacuolar degeneration greater in the hippocampus and other cerebral cortical areas than would be expected for the age of the patient. Although these same three patients had received long term L‐dopa, it seems that their pathology was related to the disease process and was not drug induced. It is possible therefore, that the dementia seen in some patients with Parkinson's disease is related to degeneration and failing function of noradrenergic and cholinergic neurotransmitter systems and not always associated with the coincidental acquisition of Alzheimer type lesions (Alzheimer's disease).
STRUCTURAL CHANGE IN MUSCLES OF THE DYSTROPHIC CHICKEN. I. QUANTITATIVE INDICES
Authors: PIZZEY J. A. , BARNARD E. A.
Published: May 2008

Pizzey J.A. & Barnard E.A, (1983) Neuropathology and Applied Neurobiology 9, 21–38

Structural change in muscles of the dystrophic chicken. I. quantitative indices

The pectoral and posterior latissimus dorsi (PLD) muscles in the dystrophic chicken show many pathological changes. At 7 weeks of age, in a strain of these birds bred for early onset of this inherited disorder, physical weakness is established and these changes can be clearly assessed. Quantitative indices of these progressive changes were obtained by light and electron microscopic analyses; these indices cover fibre hypertrophy, fibre area variation, nuclei distribution, phagocytosis and satellite cell and fibroblast populations. The dystrophic pectoral muscle at 7 weeks is more severely affected than the PLD. In the former, there is an increase of peripheral myonuclei per fibre cross‐section of over 200%, a hypertrophy factor nearly 200‐fold greater than normal and longitudinal fibre splitting in 11% of the fibres. Many foci of degeneration are also present at this early stage. Although regenerating fibres are uncommon, an increased satellite cell population is observed. These indices provide a basis for assessing the effects of in vivo drug treatments, at the level of muscle structure.
PROCEEDINGS OF THE SIXTY‐THIRD MEETING OF THE BRITISH NEUROPATHOLOGICAL SOCIETY HELD AT CHURCHILL COLLEGE, CAMBRIDGE 15–16 JULY 1982
Authors: ADAMS PRESIDENT: J. HUME
Published: May 2008

Craggs R. (introduced) & King R. H. M. (Royal Free Hospital School of Medicine, London NW3 2PF)

King R. H. M. & Thomas P. K. (Royal Free Hospital School of Medicine, London NW3 2PF) Love S. (Institute of Neurology, Queen Square, WCIN 3BG)

Jones H. B. (introduced) & Cavanagh J. B. (Institute of Neurology, London WCIN 3BG)

Kemplay Sheila (introduced) & Cavanagh J. B. (Institute of Neurology, London WClN 3BG)

Reske‐Nielsen E. & Daa Schroder H. (introduced) (Aarhus Kommunehospital, DK‐8000 Aarhus C, Denmark)

Goebel H. H., Fidzianska A. (introduced) & Osborn M. (introduced) (University of Gottingen and Max Planck Institute for Biophysical Chemistry, D‐3400 Gottingen, FRG)

Koppel H., Clarke S. (introduced) & Innocenti G. M. (introduced) (Institute of Anatomy, Lausanne, Switzerland)Anderson J. R. & Treip C. S. (Addenbrooke's Hospital Cambridge CB2 2QQ)

Sapsford I. (introduced) & Weller R. O. (Southampton General Hospital,

Reid H. (Department of Pathology, University of Manchester M13 9PT)

Deane B. R., Greenwood J., (introduced) Lantos P. L. & Pratt O. E. (Institute of Psychiatry, London SE5 8AF)

Ilgren E. B. (introduced) & Kaye A. (introduced) (Radcliffe Infirmary, Oxford OX2 6HE)

Garson J. A., Coakham H. B., Harper E. I., Kemshead J. (all introduced) & Brownell Betty. (Brain Tumour Research Laboratory, Frenchay Hospital, Bristol. Imperial Cancer Research Fund, London)

McLellan D. R., Adams J. H., Doyle D., Graham D. I, Kerr A. (introduced) & Murray L. S. (introduced) (Institute of Neurological Sciences, Glasgow G51 4TF)

Harper C. G. (introduced) & Blumbergs P. C. (introduced) (Royal Perth Hospital, Western Australia and Institute of Medical and Veterinary Science, Adelaide, South Australia)

Allsop D. (introduced), Landon M. (introduced) & Kidd M. (The Medical School, Nottingham NG7 2UH)

Wilcock G. K. (introduced), Esiri M. M. & Bowen D. M. (introduced) (Radcliffe Infirmary Oxford OX2 6HE & Institute of Neurology, London WCIN 3BG)

Mann D. M. A. & Yates P. O. (University of Manchester, Manchester M13 9PT)

Esiri M. M. & Tomlinson A. H. (introduced) (Radcliffe Infirmary, Oxford OX2 6HE)

Anderson J. R & Field H. J. (introduced) (Addenbrooke's Hospital, Cambridge CB2 2QQ and University of Cambridge, Cambridge)

Kristensson K. Leestma J. (introduced), Norrby E. (introduced) & Orvell C. (introduced) (Karolinska Institute,

Griffiths T. (introduced), Evans M. C. (introduced) & Meldrum B. S. (Institute of Psychiatry, London SE5 8AF)

McConnell P. (introduced) & Berry M. (Medical School, Birmingham, B15 2TJ)

Allen Y.S., RobertsG.W., Crow T.J. M. (Histochemistry Unit, Royal Postgraduate Medical School, London, W12 and Clinical Research Centre, Harrow, Middlesex)
STRUCTURAL CHANGE IN MUSCLES OF THE DYSTROPHIC CHICKEN. II. PROGRESSION OF THE HISTOPATHOLOGY IN THE PECTORALIS MUSCLE
Authors: PIZZEY J. A. , BARNARD E. A.
Published: May 2008

Pizzey J.A.&Barnard E.A.(1983)Neuropathology and Applied Neurobiology 9, 149–164

Structural change in muscles of the dystrophic chicken. II. Progression of the histopathology in the pectoralis muscle

Dystrophic (D) and normal (N) chicken pectoral muscle was analysed for histopathological differences from the embryo (day 20) through to the mature adult stage. A variety of indices of structural changes were used, to express the progression quantitatively. At the embryonic stage, fibroblast numbers (but not satellite cell numbers) are increased in D. D shows fibre hypertrophy discernable from about 4 days after hatching. Other abnormalities of fibre size and shape appear in D from about 2 weeks onwards. Nuclei numbers and location change characteristically in D, compared to N, from about 4 days, and these differences subsequently become very prominent. Fibre splitting and phagocytosis become significant in D from about 2 weeks onwards and increase noticeably thereafter. The later stages in D, with gross loss of muscle fibres, are also described, in the pectoral and posterior latissimus dorsi muscles. The analyses show that some of the structural changes in D precede the discernable difference in fibre type composition which develops between D and N. The changes in the muscle used provide a basis for assessing the effects of drug treatments at various stages, including the early post‐hatch period.
INTRACRANIAL CAVITY VOLUMES: A NEW METHOD AND ITS POTENTIAL APPLICATIONS
Authors: HARPER C. , KRIL JILLIAN , RAVEN D. , JONES NARELLE
Published: May 2008

Variations of brain weights and volumes often reflect pathological states. However, these parameters are more meaningful when related to intracranial volume. The most useful derived parameter is the difference between intracranial volume and brain volume expressed as a percentage (potential intracranial space). In patients with cerebral atrophy the potential intracranial space will be large, whereas in patients with space occupying lesions or brain swelling the potential intracranial space will shift towards 0%. Previously described techniques to determine intracranial volume have been unsatisfactory for routine application in the autopsy room. The technique described herein is based on the production of a permanent polyurethane cast of the cranial cavity. The casts can be formed in about 20 min with little modification of standard autopsy technique. Duplicate casts were made in twenty‐seven unselected cases and in all cases there was less than 2% error in duplicate cast volumes. The cast provides a permanent record of the size and shape of the cranial cavity and can be used to determine intracranial volume or other intracranial dimension. The usefulness of the derived parameter, potential intracranial space, is evident in some of the cases studied.
SIGNIFICANCE OF FLUID FLOW FOR MORPHOLOGY OF ACUTE HYPOXIC‐ISCHAEMIC BRAIN CELL INJURY
Authors: PALJÄRVI L. , ALIHANKA J. , KALIMO H.
Published: May 2008

It has been suggested that the presence or absence of hypoxic fluid flow during ischaemia determines the structural character of the ischaemic nerve cell injury. It is hypothesised that if a flow of fluid irrigates the injured neurons, there will be major shifts of ions and water, with consequent volumetric changes in the tissue and the ‘dark’ type of neuronal injury will result; otherwise, the structural changes are less striking and are designated as the ‘pale’ type. To test this hypothesis, rats were subjected to a global cerebral insult by filling the vasculature with a plasma substitute, which was either left stagnant or was flowing, and was either oxygenated (hypoxic flow) or nitrogenated (anoxic flow). Light and electron microscopy of the brain following 10 to 60 min of hypoxic or anoxic ischaemia disclosed that, under all three circumstances, the predominant nerve cell injury was of the pale type. The results indicate that some additional factors present in whole blood (but not in the plasma substitute) are needed during or after the insult to induce in quantity the dark type of ischaemic nerve cell injury.
IMMUNOHISTOCHEMICAL DEMONSTRATION OF AMYLOID P COMPONENT IN CEREBRO‐VASCULAR AMYLOIDOSIS
Authors: ROWE I. F. , JENSSON O. , LEWIS P. D. , CANDY J. , TENNENT G. A. , PEPYS M. B.
Published: May 2008

The presence of amyloid P component (AP) in cerebral amyloid deposits was sought using a direct immunoperoxidase technique. AP was detected in the amyloid deposits in the vessel walls but was absent from the intra‐cerebral plaques in tissue from patients with senile cerebral amyloidosis. AP was also present in the amyloid deposits in the vessel walls of patients with the Icelandic form of hereditary cerebral haemorrhage associated with amyloidosis.
ALZHEIMER'S PRESENILE DEMENTIA, SENILE DEMENTIA OF ALZHEIMER TYPE AND DOWN'S SYNDROME IN MIDDLE AGE FORM AN AGE RELATED CONTINUUM OF PATHOLOGICAL CHANGES
Authors: MANN D. M. A. , YATES P. O. , MARCYNIUK B.
Published: May 2008

A loss of nerve cells from the nucleus basalis of Meynert and the locus caeruleus together with a reduction in nucleolar volume in surviving cells was measured in twenty‐two patients with Alzheimer's disease who ranged in age from 48–92 years, and in six patients over 50 years of age with Down's syndrome who also showed extensive formation of senile plaques and neurofibrillary tangles within their cerebral cortex. When compared with age matched controls the severity of these changes was greatest in the younger patients with Alzheimer's disease, but this fell with age such that by 90 years the level of change in Alzheimer's disease approached that in old age alone. There were only slight differences in the extent of these pathological changes in those patients with Down's syndrome when compared with others of similar age with Alzheimer's disease. It is concluded that the presenile dementia of Alzheimer's disease, the senile dementia of Alzheimer type and Down's syndrome in middle age all form an age‐related continuum of pathological change.
OPENING OF THE BLOOD‐BRAIN BARRIER IN ANOLIS CAROLINENSIS. A HIGH VOLTAGE ELECTRON MICROSCOPE PROTEIN TRACER STUDY
Authors: SHIVERS R. R. , HARRIS R. J.
Published: May 2008

The tight junctions between endothelial cells of capillaries in the forebrain of Anolis carolinensis are a common component of the structural basis for the blood‐brain barrier in this reptile. The complexity of these junctions, which is apparent in platinum replicas of freeze‐fractured brain capillaries, is unchanged by treatments designed to render the blood‐brain barrier of these lizards leaky to horseradish peroxidase. An alternative route for extravasation of horseradish peroxidase, following injection of chameleons with 2.7 mg of D‐glucose to render their brain capillaries leaky, is a system of transient cytoplasmic vesicles and vesiculo‐tubular channels whose lumina may be open to the luminal or abluminal surface (or both) of the capillary endothelial cell. High voltage electron microscopy (HVEM) of 0.25 and 0.5 μm thick plastic sections of experimental brain capillary endothelium confirmed the existence of vesiculo‐tubular conduits. These channels display a sigmoid morphology and are situated in the cytoplasm at angles oblique to the luminal and abluminal surfaces of the endothelium. Occasionally, the channels spanned the entire endothelial wall of the capillary, and in such cases, appeared to connect the lumen with the brain extracellular compartment. HVEM images (including stereo pairs) of the vesiculo‐tubular channels show them to have a scalloped, irregular profile consistent with their proposed formation by fusion of pinocytotic vesicles. Also, HVEM examinations of experimental capillaries from peroxidase‐treated lizards reveal massive quantities of dense reaction product in cytoplasmic vesicles and vesiculo‐tubular membrane compartments of the endothelium, and the complex pleomorphism exhibited by these structures. Observations made in the present study suggest that as a consequence of severe hyperglycaemia, transendothelial channels form in the brain capillaries by fusion of pinocytotic vesicles generated by accelerated pinocytosis at the luminal surface of the endothelium, and subsequently serve as open routes for massive floods of tracer into the central nervous system.
NAKED AXON BUNDLES ENCLOSED BY SINGLE SEGMENTS OF MYELIN SHEATHS IN THE NERVES OF NON‐DYSTROPHIC C57BL‐ob/+ MICE
Authors: BEUCHE W. , FRIEDE R. L.
Published: May 2008

Bundles of axons enclosed by a single myelin sheath were found in the peripheral nerves of heterozygous obese C57BL‐obl + mice. Serial sections showed them to consist of two to forty naked axons encompassed by a common cuff of myelin formed by a single Schwann cell, with adjoining non‐myelinated Schwann cells protruding from either side into the cuff. These structures are similar to those found in dystrophic mice, but there were no signs of dystrophy in the obese mice. It is suggested that the axon bundles result from a disturbance of early myelination, presumably of the phase of Schwann cell proliferation or of the communication between Schwann cells and axons.
BOVINE GLYCOGENOSIS TYPE II. BIOCHEMICAL AND MORPHOLOGICAL CHARACTERISTICS OF SKELETAL MUSCLE IN CULTURE
Authors: DI MARCO P. N. , HOWELL J. McC. , DORLING P. R.
Published: May 2008

The biochemical and morphological properties of cultured skeletal muscle from calves born into a herd of cattle, which are heterozygous for glycogenosis type II, were studied over 17 days. Muscle was cultured by a modification of the explant technique in which the mononucleated cells that grew from the explants were subcultured. Skeletal muscle from animals up to 15 months of age grew in culture to produce mature, cross‐striated and spontaneously contractile myotubes. The creatine kinase activity was 310 (±45.4) mU/mg protein on day 7 when fusion was complete, and 210 (±15.1) mU/mg protein on day 17 of culture. Mature muscle cultures from animals affected by glycogenosis type II showed the characteristic biochemical and morphological abnormalities previously observed in vivo. Acid α‐glucosidase activity was absent whereas the activities of neutral α‐glucosidase, lysosomal a‐mannosidase and creatine kinase were the same as in cultures of unaffected muscle. The concentration of glycogen was higher in cultured affected muscle than in cultured unaffected muscle. On days 7, 9 and 17 of culture the glycogen concentrations were 66.7 (±2.7), 89.0 (±5.5) and 120.3 (±34.2) μg/mg protein respectively in affected muscle and 51.8 (±3.6), 59.9 (±5.4) and 55.4 (±1.0) μg/mg protein respectively in non‐affected muscle. Electron microscopic studies showed that the glycogen accumulated within the lysosomes. These results indicate that bovine glycogenosis type II is expressed in tissue culture since the cultured skeletal muscle from affected animals shows the same abnormalities as skeletal muscle in vivo.
THE EFFECTS OF MULTIPLE SEQUENTIAL EPISODES OF DEMYELINATION IN THE SCIATIC NERVE OF THE MOUSE
Authors: HALL SUSAN M.
Published: May 2008

The effects of multiple sequential episodes of demyelination in the sciatic nerve of the mouse

Intraneural injections of lysophosphatidyl choline were used to examine the effects of multiple episodes of demyelination and repair in the sciatic nerves of adult mice. It was found that the early phases of repair, from initiation of myelinolysis to the appearance of promyelinated fibres, were achieved more rapidly in multiple‐injected nerves than in single‐injected nerves. However, this lead was temporary, since subsequent remyelination was delayed in the multiple‐injected nerves until several days after it had been established in most single‐demyelinated nerves. Cell‐mediated demyelination was seen in multiple‐injected nerves, but never in single‐injected nerves. The results are discussed in terms of a the contribution of supernumerary Schwann cells to the acute stage of the programme of cellular repair; and b the possibility that the ‘normal’ response to an injection of LPC in a nerve which has previously undergone several episodes of demyelination is exacerbated by a local and self‐limiting immune‐mediated reaction.
NEURAL TISSUE GRAFTS AND REPAIR OF THE INJURED SPINAL CORD
Authors: REIER PAUL J.
Published: May 2008

Neural tissue grafting presently stands as one of the more intriguing experimental strategies being applied to the problem of spinal cord regeneration. The following annotation presents an overview of recent investigations which have shown: (1) that peripheral nerve grafts can stimulate axonal outgrowth in many descending and ascending fibre populations of the injured spinal cord and (2) that central nervous system (CNS) implants, derived from segmental and supraspinal levels of the embryonic neuraxis, may likewise have the potential for promoting repair of damaged intraspinal neural circuitries in adult and neonatal recipients.
A CEREBELLAR ABNORMALITY IN THE MOUSE WITH MOTOR END‐PLATE DISEASE
Authors: BOAKES R. J. , HARRIS J. B. , DICK D.K.
Published: May 2008

A cerebellar abnormality in the mouse with motor end‐plate disease

The murine mutant with motor end‐plate disease (med) exhibits a progressive weakness which is due to a functional denervation of skeletal muscle. It is inherited as an autosomal recessive trait and has two alleles. One of these is the jolting (medjo) mouse which also suffers from a disturbance of locomotion. Although the jolting animal was originally thought to suffer from a disorder of neuromuscular transmission, the organization of the peripheral nervous system is indistinguishable from normal and neuromuscular transmission is unimpaired. It is now clear that abnormalities in the cerebellum are responsible for the gait problems of the jolting mouse, and a preliminary morphological and neurophysiological examination of the mouse with motor end‐plate disease has shown that it also has cerebellar abnormalities. Axonal spheroids may be seen on cerebellar Purkinje cell axons in the med mouse, and the character of extra‐cellular recordings obtained from the Purkinje cells is abnormal.
CHANGES OF 5 ‐NUCLEOTIDASE ACTIVITY IN CULTURED GLIOMA CELLS
Authors: AMANO S. , SASAHARA M. , YAMADA E. , KATAOKA H. , HAZAMA F.
Published: May 2008

Amano S., Sasahara M., Yamada E., Kataoka H. & Hazama F. (1984) Neuropathology and Applied Neurobiology 11, 161–170

Changes of 5 ‐nucleotidase activity in cultured glioma cells

Changes of 5′‐nucleotidase (5′‐N) activity during subcultivation of C6 clonal rat glioma cells were studied histochemically, cytochemically and biochemically. Two different cell populations were seeded with high or low cell density respectively. 5′‐N activity in cultured cells increased continuously in both populations. The enzyme activity was always higher in the cells growing in high density than in those growing in low density, and this difference became statistically significant after 6 days of subcultivation. It seemed likely that the increase in 5′‐N activity depended on cell density, not on the frequency of mitosis. Cytochemically, enzyme activity was detected on the outer surface of the plasma membrane of cell bodies or cell processes. Strong activity was found on the processes and cell membranes where cells touched each other. In the regions where cells had intimate cell‐to‐cell contact, marked elevation of the enzyme activity was seen. Increased 5′‐N activity, which appeared to depend on cell density, was considered to be related with this cell‐to‐cell contact.
IRRADIATION AND BCNU EFFECTS IN THE STROMA IN A RAT TRANSPLANTED GLIOMA MODEL: ANALYSIS OF CEREBRAL TUMOR BED EFFECT
Authors: SPENCE A. M. , GERACI J. P. , CENT R. R.
Published: May 2008

Spence A. M., Geraci J. P. & Cent R. R. (1985) Neuropathology and Applied Neurobiology 11, 229–244

Irradiation and BCNU effects in the stroma in a rat transplanted glioma model: analysis of cerebral tumor bed effect

F‐344 rats were treated with whole‐brain fractionated or unfractionated 137Cs at several time intervals up to 6 weeks before they received intracerebral grafts of an ethylnitrosourea‐induced rat astrocytoma (36B‐10). Rats treated with a single dose of 18 Gy at 3‐ and 2 week intervals prior to tumor implantation died earlier than unirradiated control tumor recipients (P< 005, log rank sum test). Delivered 2 weeks prior to tumor grafting single doses of 10, 15, and 20, but not 5 Gy also reduced animal life span (P< 005). Similarly, a total dose of 38 but not 28‐5, 19, or 9‐5 Gy, each delivered in five daily fractions 2% weeks before tumor grafting, shortened survival (P < 005). Chemotherapy with l,3‐bis(2‐chloroethyl)‐l‐nitrosourea (133mg/kg) alone or in combination with a single dose of irradiation of 18 Gy 3 weeks preceding transplantation showed no effect on animal survival. Unirradiated control tumors demonstrated sheets of densely‐packed isomorphic astrocytes, perivascular brain parenchymal invasion, sparse, thin‐walled vasculature, frequent mitoses, but little necrosis or hemorrhage. The tumors of rats irradiated before transplantation showed large areas of confluent necrosis associated with microvascular thrombosis, edema, and multifocal acute hemorrhages. These survival results and morphological changes indicate that the cerebral tumor bed effect involves early animal death and extensive morphological changes in the tumors; and they suggest that tumor cell death in irradiated brain tumors may, in part, result from radiation‐induced vascular injury.
TRANSIENT RETINO‐INFERIOR COLLICULAR FIBRES IN NEONATAL RATS: THEIR PERSISTENCE AFTER REMOVAL OF ONE EYE AT BIRTH
Authors: KATO T. , HIRANO A. , HONDA K. , KATAGIRI T. , SASAKI H.
Published: May 2008

Kato T., Hirano A., Honda K., Katagiri T. & Sasaki H. (1985) Neuropathology and Applied Neurobiology 11, 265–272

Transient retino‐inferior collicular fibres in neonatal rats: their persistence after removal of one eye at birth

Retinal projections to the inferior colliculus in the newborn albino rat were demonstrated by intraocular injection with horseradish peroxidase. During normal development, these retino‐inferior collicular fibres disappeared by 26 days of age. However, after removal of one eye at birth, distinct retino‐inferior collicular fibres arising from the remaining eye were preserved contralaterally in rats at 26 days of age.
PRIMARY DEMYELINATION IN THE CENTRAL NERVOUS SYSTEM OF CATS
Authors: COOK R. D. , WILCOX G. E.
Published: May 2008

Cook R. D. & Wilcox G. E. (1985) Neuropathology and applied Neurobiology 11, 361–367

Primary demyelination in the central nervous system of cats

Primary demyelinating lesions have been observed in the central nervous system of 16 (approximately 7%) of a total of 235 clinically normal cats. The size of the lesions varied from small perivascular lesions in white matter to a large lesion occupying the diameter of an optic nerve. Intracytoplasmic inclusions consisting of tubular structures were common to all lesions examined by electron microscopy. The features of these feline lesions are briefly compared with those seen in multiple sclerosis.
VENTRAL ROOT AXONOPATHY AND ITS RELATION TO THE NEUROFIBRILLARY DEGENERATION OF LOWER MOTOR NEURONS IN ALUMINUM‐INDUCED ENCEPHALOMYELOPATHY
Authors: TRIARHOU L. C. , NORTON J. , BUGIANI O. , GHETTI B.
Published: May 2008

Triarhou L. C, Norton J., Bugiani O. & Ghetti B. (1985) Neuropathology and Applied Neurobiology 11, 407–430

Ventral root axonopathy and its relation to the neurofibrillary degeneration of lower motor neurons in aluminum‐induced encephalomyelopathy.

The injection of metallic aluminum (Al) into the cerebrospinal fluid of adult rabbits induces neurofibrillary degeneration of lower motor neurons. We studied the ventral roots and the corresponding motor neurons of Al‐treated animals to clarify the modality and extent of reaction of the axon in relation to the severity of perikaryonal involvement. Moreover, the involvement of dorsal root ganglion cells was compared to that of lower motor neurons. Rabbits received 015 ml of a 1% Al slurry intracisternally and were perfused through the heart with aldehydes at 14–62 days after injection. Spinal cords and roots were embedded in Epon and examined morphologically and by morphometric techniques. An axonopathy was observed in the ventral roots, characterized by neurofilamentous axonal swellings and myelin attenuation in several size classes of axons. Results obtained from axons traced in serial sections indicate that there may be a unifocal or a multifocal axonopathy. Dorsal root ganglion cells showed milder changes by comparison with motor neurons and their axons in the ventral roots. The most severe axonopathy was associated both with an incidence of 66–81% of motor neurons showing neurofibrillary degeneration and with a rapidly progressing motor weakness. These findings are related in the discussion section to the pathological expression of human neurological disorders in which the lower motor neurons are selective targets.
HISTOCHEMICAL FIBRE TYPING AND ULTRASTUCTURE OF THE SMALL FIBRES IN DUCHENNE MUSCULAR DYSTROPHY
Authors: WATKINS S. C. , CULLEN M. J.
Published: May 2008

Watkins S. C. & Cullen M. J. (1985) Neuropathology and Applied Neurobiology 11, 447–460

Histochemical fibre typing and ultrastructure of the small fibres in Duchenne muscular dystrophy

Fibre type differentiation was carried out on 20 biopsies from Duchenne Muscular Dystrophy (DMD) sufferers using the acid‐preincubated reaction for myofibrillar ATPase. Fibres, classified as either type 1, type 2 or 2C, were counted and their minimum diameters (least fibre axis) measured. Particular attention was paid to the population of small fibres that becomes increasingly prominent with the increasing age of the patient. Type 1 fibres were always predominant in the fibre population as a whole. The numbers of type 2 fibres declined with the increasing age of the patients while the numbers of 2C fibres increased. All fibre types were represented in the population of small fibres and the ratio of the numbers of types 1:2: 2C fibres was approximately 1:1:3. Ultrastructural examination of the small fibres showed them to be at varying stages of regeneration and differentiation. The continuous presence of regenerating fibres in DMD while the muscles are wasting implies that while regeneration can be initiated it becomes increasingly constrained or restricted as the disease progresses. The cause of this restriction and whether it is related to the basic genetic lesion is unknown. It is suggested that the accumulation of fibrous connective tissue interferes with growth, either directly, in the formation of pseudomyotendinous junctions, or indirectly, by reducing nutrient exchange with the vascular system.
CURRENT TOPICS IN NEUROPATHOLOGY CUSHING'S DISEASE
Authors: McNICOL A. M.
Published: May 2008

McNicol A. M. (1985) Neuropathology and Applied Neurobiology 11, 485–498

Cushing's disease

The application of modern investigative techniques, particularly electron microscopy and immunohistochemistry, to the pituitary gland in Cushing's disease have confirmed that in the majority of cases (up to 90% in some series) the disease is due to a corticotroph microadenoma. It has also been shown that the tumours may produce not only ACTH, but also other peptides derived from the same precursor molecule, pro‐opiomelanocortin and, in a small minority of cases, other pituitary hormones (e.g. prolactin). Since these peptides are known to have physiological actions they may account for some of the varied symptoms and signs of Cushing's disease. Because of the high incidence of single tumours the treatment of choice in many centres has become selective adenomectomy by the transsphenoidal route. However, a minority of cases appear to be the result of primary hypothalamic or central abnormalities and this may account for the identification of a normal pituitary gland or of corticotroph hyperplasia (with or without tumour formation). It is not possible at the present to identify these groups of patients on the basis of biochemical testing. It is hoped that detailed prospective studies correlating hormone secretion, responses to biochemical testing and detailed investigation of pathological tissue will provide further insight into the pathogenesis of particular variants of the disease.
SPONGIFORM ENCEPHALOPATHY: A NEUROCYTOLOGIST'S VIEWPOINT WITH A NOTE ON ALZHEIMER'S DISEASE
Authors: GRAY E. G.
Published: May 2008

Gray E.G. (1986) Neuropathology and Applied Neurobiology 12, 149–172

Spongiform encephalopathy: a neurocytologist's viewpoint with a note on Alzheimer's disease

Ultrastructural studies of spongiform encephalopathy (SE) reveal no very early pathological changes in kuru where membrane lamellation has been reported. This observation is challenged. In the later stages of SE, two main theories are examined‐the spiroplasma theory and the prion (6 nm filament) theory. Neither are sufficiently convincing at present. In my own ultrastudies of Creutzfeldt‐Jakob disease brain, extensive dismantling of the dendritic microtubule cytoskeleton has been observed. Loss of dendritic cytoskeleton implies loss of dendritic cytotransport with abolition of postsynaptic events. This would explain neurological symptoms and death where other causes, pneumonia etc. are not involved. My experimental model, involving depletion or loss of dendritic microtubules, indicates that spongy vacuoles may be fixation artifacts. In a brief consideration of Alzheimer's disease, loss of dendritic microtubules has also been observed, with the implications mentioned above. Finally, the neuritic plaque will be considered.
INTRANUCLEAR VACUOLES IN CREUTZFELDT‐JAKOB DISEASE
Authors: CERVOS‐NAVARRO J. , CRUZ‐SANCHEZ F. , GIMENO‐ALAVA A. , FERSZT R.
Published: May 2008

In an electron microscopic study of brain biopsy material from a case with Creutzfeldt‐Jakob disease intranuclear vacuoles containing membrano‐vesicular structures were found. To our knowledge this finding has not been previously reported in human spongiform encephalopathies. It may represent a specific alteration associated with Creutzfeldt‐Jakob disease, and suggests the possibility of nuclear infection.
IDIOPATHIC PARKINSON'S DISEASE AND THE LEWY BODY DISORDERS
Authors: GIBB W. R. G.
Published: May 2008

Idiopathic Parkinson's disease and the Lewy body disorders

A common clinical manifestation of idiopathic Lewy body disease is levodopa responsive idiopathic Parkinson's disease. Infrequently features such as dementia or autonomic failure predominate. The Lewy body is also reported; (a) as an incidental finding in 7–10% of normal individuals mostly over the age of 60 (b) as an incidental sporadic finding in Parkinson's syndrome from other causes, mostly over the age of sixty; (c) in an additional group of degenerative disorders at a younger age, some with familial inheritance. The incidental finding of Lewy bodies can precede clinical Parkinson's disease. It is thought they do not occur as an age‐related feature, although this cannot be stated with certainty. Current evidence suggests that about 10% of the population may possess the pathological substratum for idiopathic Parkinson's disease.
THE EFFECT OF INHIBITING SCHWANN CELL MITOSIS ON THE RE‐INNERVATION OF ACELLULAR AUTOGRAFTS IN THE PERIPHERAL NERVOUS SYSTEM OF THE MOUSE
Authors: HALL SUSAN M.
Published: May 2008

The effect of inhibiting Schwann cell mitosis on the re‐innervation of acellular autografts in the peripheral nervous system of the mouse

Reactive gliosis in the zone immediately proximal to transection of the sciatic nerve has been inhibited by intraneural injection of mitomycin C, an anti‐mitotic agent known to arrest Schwann cell division after transection, crush or demyelination. Mitomycin C‐pretreated proximal stumps were subsequently sutured to cellular or acellular autografts (0–5 cm long) and neurite growth into and within the grafts was examined during a 5‐week post‐operative period. Neurites grew into cellular autografts and became associated with the resident population of Schwann cells within the grafts, to the extent that remyelination was well established in the majority of Schwann cell basal lamina tubes by week 5 post‐suture. In marked contrast, very few neurites grew into acellular grafts during this time, and where axons and Schwann cells were seen they tended to be grouped in ‘minifascicles’. The results suggest that neurite outgrowth from proximal stumps is dependent upon active Schwann cell participation.
MULTIFOCAL ISCHAEMIC ENCEPHALOMYELOPATHY ASSOCIATED WITH FIBROCARTILAGINOUS EMBOLI IN THE LAMB
Authors: JEFFREY M. , WELLS G. A. H.
Published: May 2008

Multifocal ischaemic encephalomyelopathy associated with fibrocartilaginous emboli in the lamb

Multifocal, arterial, fibrocartilaginous embolism of the cervical spinal cord, medulla oblongata and cerebellum is described in a neonatal lamb. The emboli contained mucosubstances which, by the Alcian blue critical electrolyte concentration method, were identified as mainly keratan sulphate. This composition indicates the probable origin of emboli from the nucleus pulposus of intervertebral discs. Possible modes of entry of such material into the spinal cord vasculature are reviewed and a mechanism proposed to explain the localization of emboli in spinal cord, brain stem and cerebellar arteries in this case.
THE EFFECTS OF THYROID HORMONE ON DIFFERENTIATION AND NEUROFILAMENT EXPRESSION IN RAT BRAIN AGGREGATING CULTURES
Authors: WOODHAMS P. L. , ATTERWILL C. K. , BALAZS R.
Published: May 2008

The effects of thyroid hormone on neural development in vitro were studied using rat fetal forebrain aggregating cultures. They were examined morphologically after growth for 21 days in medium containing fetal calf serum (S+), in a chemically denned medium (S‐), or in serum‐free medium containing 30 nM triiodothyronine (T3). Aggregates grown in S+ showed certain morphological differences compared to those grown in the absence of serum: a glia limitans was present in the former, but not the latter, which were further characterized by a marginal zone rich in fibres and containing few cells. Immunocytochemistry using a monoclonal antibody against neurofilaments showed that immunostaining was most pronounced in aggregates grown in T3 (especially in the marginal zone) and weakest in those grown in S+. Quantitative estimation using an immunoadsorbent assay confirmed that T3 medium increased the amount of neurofilament protein in the aggregates, consistent with the view that thyroid hormone promotes neural development in vitro.
REGENERATION IN CELLULAR AND ACELLULAR AUTOGRAFTS IN THE PERIPHERAL NERVOUS SYSTEM
Authors: HALL S. M.
Published: May 2008

The regeneration that occurs in cellular autografts of sciatic nerve has been compared with that seen in acellular models prepared either by cycles of alternating freezing and thawing, or by detergent‐extraction. The responses to either fresh or pre‐degenerate grafts (cellular and acellular) have been examined electron microscopically. It was found that whereas neurites grew into a fresh autograft and rapidly re‐established functional relationships with vital Schwann cells lying in bands of Biingner within the graft, penetration of acellular grafts was less efficient. Many basal lamina tubes in the acellular grafts remained either empty or filled with debris‐laden macrophages for the first 2 weeks after suture, although subsequently reinnervation did occur. The roles of Schwann cells, macrophages and basal laminae during reinnervation are discussed.
LIGHT AND ELECTRON MICROSCOPICAL STUDIES OF THE IMMUNOPEROXIDASE STAINING OF MULTIPLE SCLEROSIS PLAQUES USING ANTISERA TO A FELINE‐DERIVED AGENT AND TO GALACTOCEREBROSIDE
Authors: COOK R. D. , FLOWER R. L. P. , DUTTON N. S.
Published: May 2008

Antibodies have been raised to two agents (CCA147 and MV631) that were isolated from central nervous tissue of cats. The cells co‐cultivated with these agents are characterized by the presence of cytoplasmic inclusions consisting of 16–18 nm diameter tubular elements morphologically similar to inclusions seen in a demyelinating condition in cats and to inclusions described as ‘curved linear profiles’ in multiple sclerosis (MS) plaques. The peroxidase‐labelled antibodies to CCA147 and MV631 stain these inclusions in MS plaques as well as small virus‐like particles. The antisera do not stain normal white matter either in MS or non‐MS brain tissue. The staining reaction of one agent is blocked by pretreatment with antisera to the other agent and also by pretreatment with MS sera but not by normal human sera. Peroxidase‐labelled antibody to galactocerebroside stains normal myelin and myelin debris within MS plaques but does not stain the ‘curved linear profiles’ that are stained by the labelled antibodies to the feline‐derived agents. The results show that the ‘curved linear profiles’ described in MS plaques are not myelin degradation products, but are comparable to the nucleocapsids of morbilliviruses. In addition, the small virus‐like particles are morphologically similar to morbillivirus virions. The results are discussed with particular emphasis on the features of the morbilliviruses, canine distemper and measles viruses.
HUMAN AFRICAN TRYPANOSOMIASIS (T.b. GAMBIENSE): A STUDY OF 16 FATAL CASES OF SLEEPING SICKNESS WITH SOME OBSERVATIONS ON ACUTE REACTIVE ARSENICAL ENCEPHALOPATHY
Authors: ADAMS J. HUME , HALLER L. , BOA F. Y. , DOUA F. , DAGO A. , KONIAN K.
Published: May 2008

The principal clinical and pathological findings in 16 fatal cases of human African trypanosomiasis caused by T.b. Gambiense are described. The changes in the brain took the form of a non‐specific lymphoplasmacytic meningo‐encephalitis of varying intensity. Other features included morular cells, diffuse microglial hyperplasia, and large reactive astrocytes in the white matter. Carditis was identified in 10 cases. Acute reactive arsenical encephalopathy appeared to be the principal cause of death in 10 patients. Convulsions figured prominently in this type of encephalopathy in seven patients and were sufficiently severe to produce hypoxic brain damage. In three cases of acute reactive arsenical encephalopathy the structural changes in the brain were those of acute haemorrhagic leucoencephalopathy.
LEIGH'S DISEASE ‐SEVERAL NOSOLOGICAL ENTITIES WITH AN IDENTICAL HISTOPATHOLOGICAL COMPLEX?
Authors: WALTER G. F. , BRUCHER J. M. , MARTIN J. J. , CEUTERICK C. , PILZ P. , FREUND M.
Published: May 2008

Although Leigh's disease corresponds to a quite distinct histopathological complex, clinical and biochemical findings may be very divergent. By the description of classical and borderline cases and by the comparison with cases from the literature, it is suggested that Leigh's disease encompasses several nosological entities related to different disorders of the energy metabolism. They produce an identical histopathological complex. New evidence for a cerebral mitochondriopathy is also given.
LECTIN BINDING IN MENINGIOMAS
Authors: KLEINERT R. , RADNER H.
Published: May 2008

Forty‐two meningiomas of different morphological sub‐type were examined to determine their pattern of binding to 11 different lectins which characterize cell surface components such as carbohydrate residues. Histiocytic and xanthoma cells within meningiomas could be demonstrated with six different lectins: wheat germ agglutinin (WGA), peanut agglutinin (PNA) Bauhinia purpurea agglutinin (BPA), Helix pomatia agglutinin (HPA), Vicia fava agglutinin (VFA) and Soyabean agglutinin (SBA). Vascular elements including endothelial cells and intimal cells, bound Ulex europaeus agglutinin type 1 (UEA 1), WGA and HPA. The fibrous stroma in fibrous and fibroblastic meningiomas bound PNA, Laburnum alpinum agglutinin (LAA) and SBA. Tumour cells in meningotheliomatous meningiomas and some areas of anaplastic meningiomas bound Concanavalin A, PNA, LAA and VFA whereas tumour cells in fibrous and fibroblastic meningiomas bound BPA, LAA and VFA. Lectin binding has proved to be of value in detecting histiocytic and xanthoma cells together with vascular elements within meningiomas. In addition, the different lectin binding patterns allow different histological sub‐types of meningioma to be distinguished although the biological significance of the binding patterns is unclear.
‘EXPANDING CEREBRAL LACUNAE’ IN A HYPERTENSIVE PATIENT WITH NORMAL PRESSURE HYDROCEPHALUS
Authors: DEROUESNÉ C. , GRAY F. , ESCOUROLLE THE LATE R. , CASTAIGNE P.
Published: May 2008

A hypertensive patient who had been treated successfuly for normal pressure hydrocephalus (NPH), died from a left thalamic haemorrhage. Neuropathological examination showed recent and old thalamic haematomas and numerous parenchymal cavities or ‘cerebral lacunae’. Two lacunae bulged into the lateral ventricles, and had all the characteristics of so called ‘expanding lacunae’. They were surrounded by a single layer of epithelial‐like cells, contained a normal, patent, arteriole, and presented as space occupying lesions. Only two similar cases have been reported previously. The complexity of the neuropathological features of ‘cerebral lacunae’ is emphasized and the relationships between cerebral hypertensive disease, NPH, and expanding lacunae are discussed.
AN IMMUNOHISTOCHEMICAL STUDY OF THE GERMINAL LAYER IN THE LATE GESTATION HUMAN FETAL BRAIN
Authors: GOULD S. J. , HOWARD S.
Published: May 2008

In the cerebral lateral ventricle of the human fetus, the embryonic ventricular and subventricular zones (VZ and SVZ) persist into the latter half of gestation, particularly in the lateral wall. The SVZ is usually referred to as the germinal layer at this stage. The VZ is gradually replaced by ependyma, a single epithelial layer composed of tanycytes and ciliated columnar cells. In the prematurely born infant, the germinal layer is frequently the site of haemorrhage, the incidence of which diminishes with increasing maturity. There are many contributory pathogenetic factors but the structure of the germinal layer itself is considered important. It contains numerous, thin walled vessels in a cellular matrix which demonstrates little fibrillary background. Immunohistochemical evidence of glial differentiation in the germinal layer was sought in 21 preterm brains, using antibody to glial fibrillary acidic protein (GFAP). Early immunoreactivity was due to GFAP positive tanycyte fibres. Subsequently, associated with astrocyte differentiation, there was progressive development of a glial fibre network. It is suggested that the increase in glial fibres may be a significant factor in capillary stabilization, and in the inverse relationship between gestation of the infant and the risk of intracerebral haemorrhage. The possible structural significance of the tanycyte is also highlighted.
PLEOMORPHIC XANTHOASTROCYTOMA IN A 62‐YEAR‐OLD MALE
Authors: MACKENZIE J. M.
Published: May 2008

Pleomorphic xanthoastrocytoma has been described as a distinct clinicopathological entity with a relatively favourable prognosis. However, tumours closely resembling this entity have been shown to have the potential for aggressive behaviour, and to represent, on closer scrutiny, a number of disparate neoplasms. A case is described which, although otherwise typical of pleomorphic xanthoastrocytoma, occurred in a man of 62 years, and it is suggested that it should be considered a specific histological, rather than a clinicopathological entity.
NUCLEAR AND NUCLEOLAR DAMAGE IN ADRIAMYCIN‐INDUCED TOXICITY TO RAT SENSORY GANGLION CELLS
Authors: CAVANAGH J. B. , TOMIWA K. , MUNRO P. M. G.
Published: May 2008

A single dose (10 mg/kg) of Adriamycin was given to 23 adult Wistar rats and the spinal ganglia were studied from 6 h to 15 days after. As previously described, this drug results in the appearance of ‘clear’ areas in the nuclei of rat spinal ganglion cells as seen by light and by electron microscopy. The ‘clear’ areas become less conspicuous during the week before the onset of cytoplasmic degeneration. In addition, nucleolar changes become increasingly evident with time after injection. Fibrillar centres enlarge and nucleolar segregation is present from 24 h onwards, although the latter is invariably partial and more readily seen with the electron microscope. Nucleolar fragmentation is seen more frequently from 3 days onwards and nucleolar enlargement is common from 6 days. Early cytoplasmic abnormalities are associated with pronounced loss of Nissl substance. Adriamycin must bind extensively to nuclear DNA in spinal ganglion cells, causing the ‘cleared’ nuclear areas and the changes in dense chromatin. In addition, the binding of Adriamycin to nucleolar DNA with disturbance to nucleolar functions must be important in producing later cytoplasmic changes that precede cell death. There are thus similarities between the action of Adriamycin on these cells and those of Cisplatin, although in the latter intoxication the nuclear effects are significantly less prominent.
THE TOXICITY AND NEUROPATHOLOGY OF DIMETHYLETHYLTIN AND METHYLDIETHYLTIN IN RATS
Authors: ALDRIDGE W. N. , VERSCHOYLE R. D. , THOMPSON CAROL A. , BROWN A. W.
Published: May 2008

Triethyltin causes an increase in brain water with vacuolation of myelin sheaths, whereas trimethyltin is selectively damaging to neurons, especially of the hippocampal formations, causing chromatolysis, accumulation of cytoplasmic dense bodies and often cell death. The effects on rats of the analogues, dimethylethyltin and methyldiethyltin (oral LD50 14mg/kg and 7.5–10.0 mg/kg respectively) are now reported. The dimethylethyl compound produces functional changes resembling those caused by trimethyltin, while the methyldiethyl compound causes responses similar to those produced by triethyltin. Structurally, however, the dimethylethyl compound, while producing marked nerve cell changes of the trimethyltin type also causes moderate vacuolation of myelin sheaths. By contrast, methyldiethyltin causes marked vacuolation of myelin sheaths of the triethyltin type and relatively minor neuronal changes of the trimethyltin type. These findings are discussed in terms of the structure‐activity relationships of trialkyltin compounds.