bluuebunny/crossref_metadata_2025 huggingface dataset:
Early unsuspected neuron and axon terminal loss in scra pie‐infected mice revealed by morphometry and immunocytochemistry
Authors: Jeffrey M. , Fraser J. R. , Halliday W. G. , Fowler N. , Goodsir C. M. , Brown D. A.
Published: May 2008

Neuronal loss is often quoted as an element of the pathology of the transmissible spongiform encephalo‐pathies, but few data are published. To determine whether neuronal loss is a salient feature of murine scrapie, and whether there is a relationship with the other hallmark lesions of scrapie we compared the numbers of neurons, severity of vacuolation, axonal bouton density and distribution of prion protein (PrP) in the dorsal lateral geniculate nucleus (dLGN) following intraocular infection of C57BL/FaBtDk mice with ME 7 scrapie. This route of infection limits the initial spread of infection to the retinal efferents, thus directing infectivity and subsequent pathological changes to the dLGN which is a major projection of the optic nerve. Morphometric assessment of neuron number in the dLGN was made on semi‐serial sections from five infected and five normal brain injected controls at four 50‐day intervals during the incubation period, and on terminally affected mice. The number of neurons decreased from around 20 000 at 50 days to under 1000 in the terminal group. Significant loss was identified in individual mice at 150 days post‐infection, coincident with the onset of vacuolation: neuron number was found to have an inverse relationship to the severity of vacuolation. Axonal boutons in the dLGN (demonstrated by synaptophysin immunolabelling) were reduced at 200 days, and virtually absent in terminal mice. The intensity of PrP immunostaining progressively increased from 150 days, and in a separate experiment PrP was detected from 175 days by polyacrylamide gel electrophoresis of brain extracts. These results show that early neuronal loss is a significant feature of experimental scrapie infection, and the possible mechanisms of this degeneration are discussed.
The neuronal ceroid‐Iipofuscinoses (Batten disease): comparative aspects
Authors: Jolly R. D. , Palmer D. N.
Published: May 2008

The ceroid‐lipofuscinoses are a group of inherited neurodegenerative diseases of human beings characterized by the accumulation of a fluorescent lipopigment in neurons and other cells within the body. There is usually atrophy of both brain and retina with preferential loss of particular neurons. Biochemically, the diseases divide into at least two groups, i.e. those that accumulate subunit c of mitochondrial ATP synthase and those that do not. Dolichol pyrophosphate linked oligosaccharides are also present in storage material. As the underlying biochemical anomalies are not known, the various clinicopathological entities are classified on clinical grounds, by age of onset and, to a lesser extent, by the course of the disease. The best recognized diseases are infantile, late infantile, early juvenile, juvenile and adult onset forms but other variants occur indicating considerable heterogeneity within the group. The infantile, late infantile and juvenile diseases are not allelic. Analogous diseases occur in a variety of animal species. That in the sheep has been extensively studied as a model of the human disease and is the prototype subunit c storage disease.
The neonatal progeroid syndrome (Wiedemann‐Rautenstrauch) and its relationship to Pelizaeus‐Merzbacher's disease
Authors: Ulrich J. , Rudin C. , Bubl R. , Riederer B. M.
Published: May 2008

The neuropathology of a clinically well‐documented case of the neonatal progeroid syndrome Wiedemann‐Rautenstrauch is described. The most striking feature was a nearly complete absence of mature myelin in the brain. When immunohistochemistry for myelin basic protein was applied, some subcortical nerve fibres were accompanied by immature myelin sheaths. The neuropathology corresponds exactly to that of Pelizaeus‐Merzbacher disease (Seitelberger type). Furthermore, this morphology, with the presence of myelin basic protein in the absence of mature myelin sheaths is reminiscent of the early stages of myelination in the newborn. From a brief review of the literature on Wiedcmann—Rautenstrauch syndrome, we conclude, that the neuropathology of the syndrome is heterogeneous, and that there is a relationship between the progeroid aspect and pathological myelination.
Focal brain damage enhances experimental allergic encephalomyelitis in brain and spinal cord
Authors: Phillips M. J. , Weller R. O. , Kida S. , Iannotti F.
Published: May 2008

The immunological basis of multiple sclerosis (MS) is well recognized but the factors inducing MS lesions are unclear. In this study, we test the hypothesis that focal brain injury, inflicted during the pre‐clinical stages of experimental allergic encephalomyelitis (EAE), will enhance the severity of immunological damage in the cerebral hemispheres and spinal cord. Acute EAE was induced in 30 Lewis rats by the injection of guinea pig spinal cord homogenate in complete Freund's adjuvant. A cryolesion to the surface of the left cerebral hemisphere was induced at 3 days (n=6) or 8 days (n=10) post‐inoculation (pi) and animals were killed at 15 days pi. Control animals were EAE only (n = 9), cryolesion only (n=4), EAE and sham cryolesion (n=5) and normal animals (n=3). Brain and spinal cord were stained by immunocytochemistry using W3/13 (T‐lymphocytes) OX6 (MHC Class II) and GFAP (astrocytes) antibodies. The results showed a 2‐fold increase in the number of EAE lesions in the brain with significant and widespread increase of MHC Class II antigen expression by microglia, in the cryolesion EAE 8 days p.i when compared with EAE only animals. The pattern of enhancement suggests that it is due to (i) local spread of tissue or serum factors from the cryolesion; (ii) neural factors affecting remote regions of the CNS; (iii) stimulation of the immune system which may occur due to products of brain injury draining to regional cervical lymph nodes. Investigation of the mechanisms involved may prove fruitful in establishing factors which initiate, aggravate or ameliorate brain damage in multiple sclerosis.
Apoptotic neurons in brains from paediatric patients with HIV‐I encephalitis and progressive encephalopathy
Authors: Gelbard H. A. , James H. J. , Sharer L. R. , Perry S. W. , Saito Y. , Kazee A. M. , Blumberg S. M. , Epstein L. G.
Published: May 2008

The pathogenesis of human immunodeficiency virus type 1 (HIV‐1) associated dementia in adults involves neuronal loss from discrete areas of the neocortex and subcortical regions, but the mechanism for neuronal death is poorly understood. Gene‐directed cell death resulting in apoptosis is thought to be a normal feature of neuronal development, but little is known about neuronal apoptosis in disease states. We investigated whether HIV‐1 infection of the central nervous system is spatially associated with apoptosis of neurons. Using an in situ technique to identify newly cleaved 3′‐OH ends of DNA as a marker for apoptosis, we demonstrate the presence of apoptotic neurons in cerebral cortex and basal ganglia of children that had HIV‐1 encephalitis with progressive encephalopathy. Furthermore, an association was observed between the localization of apoptotic neurons and perivascular inflammatory cell infiltrates containing HIV‐1 infected macrophages and multinucleated giant cells. Apoptotic neurons and p24–positive macrophages were observed infrequently in cerebral cortex and basal ganglia in children with HIV‐1 infection without encephalitis or clinical encephalopathy. In nine control (HIV‐1 negative) brains, ranging from the first post‐natal month of life to 16.5 years of age, infrequent neuronal apoptosis was observed in three cases. These findings suggest that neuronal apoptosis is unlikely to be associated with post‐natal development except in early post‐natal germinal matrix, and that it may instead represent the end result of specific pathological processes, such as HIV‐1 encephalitis.
Grumose or foamy spheroid bodies involving astrocytes in the human brain
Authors: Arai N.
Published: May 2008

Grumose or foamy spheroid bodies (GFSB), which correspond to the classical pathological description, ‘grumose degeneration’, are described. By light microscopy, GFSB are faintly eosinophilic and spheroidal structures with a foamy appearance in haematoxylin and eosin stains; they vary from 10 to 50 μm in diameter and contain amorphous debris‐like material. Some GFSB, however, contain a varying amount of eosinophilic grumose aggregates, some of which are randomly stained with periodic acid Schiff (PAS), Schmorl, Berlin blue, Grimelius or silver methods. The Gallyas stain, on the other hand, usually stains the contents of GFSB black or brown. Immunohistochemically, most GFSB are ubiquitin‐positive. Characteristically glial fibrillary acidic protein is associated with some GFSB giving a foamy appearance. Ultrastructurally, GFSB consist of dense bodies of various sizes and configuration. Glial fihrillary bundles and astrocytic punclate adhesions are occasionally observed associated with GFSB. Anatomically, GFSB are observed preferentially in the rostroventral parts of both the substantia nigra pars reticulata and the globus pallidus in a number of human neurodegenerative diseases and aged brains. GFSB, however, appear outside the above regions in various circumstances such as trauma, infarction and astrocytomas. In conclusion, GFSB are ubiquitinated structures closely related to astrocytes in their formation and with a preferred location in the deep regions of the basal ganglia.
Microglial inter leukin‐1α expression in brain regions in Alzheimer's disease: correlation with neuritic plaque distribution
Authors: Sheng J. G. , Mrak R. E. , Griffin W. S. T.
Published: May 2008

Interleukin‐1α‐immunoreactive (IL‐1α+) microglia are prominent components of neuritic plaques in Alzheimer's disease, and may be important in the evolution of neuritic plaques from diffuse amyloid deposits. Neuritic plaques show a characteristic distribution across cerebral regions and are absent in the cerebellum of patients with Alzheimer's disease. We used single‐ and dual‐immunohistochemical labelling to investigate the possibility that the expression of IL‐1α is correlated with this regional distribution of neuritic (tau 2‐immunoreactive, tau 2+) plaques. In Alzheimer's disease, tau 2+ neuritic plaques occurred with increasing frequency in grey matter of frontal and occipital lobes, temporal lobe, and hippocampus. There were positive correlations between the regional patterns of distribution of activated IL‐1α+ microglia and tau2+ neuritic plaques as well as between activated IL‐1α+ microglia and activated astrocytes. No activated IL‐1α+ microglia, tau 2+ neuritic plaques, or activated astrocyies were observed in cerebellum of these Alzheimer patients. These regional relationships between activated IL‐1α+ microglia, tau 2+ neuritic plaques, and activated astrocytes, together with the established functions of IL‐1, support a causal association between the overexpression of IL‐1 and the evolution of β‐amyloid deposits into neuritic plaques in Alzheimer's disease.
Cytolytic effects of autologous lymphokine‐activated killer cells on organotypic multicellular spheroids of gliomas in vitro
Authors: Kaaijk P. , Troost D. , Das P. K. , van den Berg F. , Leenstra S. , Bosch D. A.
Published: May 2008

Knowledge about lymphokine‐activated killer (LAK) cell infiltration and LAK cell cytotoxicity is essential to improve the effectiveness of LAK cell therapy against gliomas. In the present study, organotypic multicellular spheroids (OMS) of glioma tissue were used as a culture model to study the effects of LAK cells on gliomas. Compared to tumour cell lines and spheroids derived from tumour cell lines, OMS have several advantages with respect to preservation of tumour cell heterogeneity and the maintenance of the tumour architecture, e.g. capillaries and extracellular matrix. Four glioma specimens, obtained at surgery, were cultured directly on agarose to form OMS, which were then co‐cultured with either autologous LAK cells or autologous non‐activated peripheral blood lymphocytes (PBLs). After various time periods of co‐cultivation. the OMS were fixed and examined both histologically and immunocytochemically. The present results showed that LAK cells infiltrated the OMS completely within 24 h of co‐cultivation and severe cellular damage was observed, whereas PBLs infiltrated the OMS poorly and there was only marginal cellular damage. The present study indicates that OMS of gliomas provide an experimental model to investigate the infiltration and cytotoxicity of LAK cells on glioma tissue in vitro.
A comparison of leucocyte responses to heat‐killed bacillus Calmette‐Guérin in different CNS compartments
Authors: Matyszak M. K. , Perry V. H.
Published: May 2008

We have previously shown that heat‐killed bacillus Calmette‐Guérin (BCG) injected into the CNS parenchyma does not produce a typical delayed‐type hypersensitivity (DTH) response [23]. In this paper we have compared the initial leucocyte response in the CNS parenchyma, ventricles and skin to gain insight into the mechanisms by which the DTH response in the CNS might be controlled. We have found that 105 organisms of heat‐killed BCG injected into either the CNS parenchyma or the lateral ventricles produced a rapid neutrophil response at the site of the injection, which was comparable with that in the skin. The neutrophil response resolved within the first week. Unlike the neutrophil response, the mononuclear phagocyte response in the CNS parenchyma was much smaller than that seen in the ventricles and the skin and it resolved within 4 weeks. Furthermore, the myelomonocytic response in the CNS parenchyma failed to clear the BCG. The acute inflammatory response in the choroid plexus/ventricles and skin developed with a similar time‐course into a typical DTH response. After the first week, lesions at these two sites were composed predominantly of T‐cells and macrophages. DTH lesions were still detected at both sites after 6 weeks. The failure of the immune system to recognize foreign antigens sequestrated in the CNS parenchyma may have significant implications especially in studies of inflammatory responses in the CNS of unknown origin.
Nerve and muscle biopsy in a case of hereditary motor and sensory neuropathy type III with basal lamina onion bulbs
Authors: Bomemann A. , Hansen F. J. , Schmalbruch H.
Published: May 2008

A. Bornemann, F. J. Hansen and H. Schmalbruch (1996) Neuropathology and Applied Neurobiology 22, 77‐81

Nerve and muscle biopsy in a case of hereditary motor and sensory neuropathy type III with basal lamina onion bulbs

A girl presented at age 8 months with generalized hypotonia and areflexia. The parents were unrelated and without symptoms. At the age of 2 years and 10 months she was able to stand and walk with support. Intellectual development was normal. The mean fibre size in the lateral vastus muscle was normal, the variability was slightly increased. Type I and II fibres tended to be aggregated, but there was no type grouping. Motor and sensory nerve conduction velocities were less than 6 m/s. The sural nerve lacked myelin sheaths, and large non‐myelinated axons were surrounded by concentric layers (‘onion bulbs’) of basal lamina material. The disease was classified as ‘autosomal recessive hereditary motor and sensory neuropathy type III(HMSN (III) with basal lamina onion bulbs’. The muscle biopsy findings suggest that congenital amyelination or hypomyelination does not necessarily result in neurogenic atrophy.
Prion protein genotype and pathological phenotype studies in sporadic Creutzfeldt‐Jakob disease
Authors: MacDonald S. T. , Sutherland K. , Ironside J. W.
Published: May 2008

A comparative semi‐automated morphometric study was performed on the distribution of prion protein, spongiform change and astrocytosis in the brains of nine cases of sporadic Creutzfeldt‐Jakob disease of differing genotype at the methionine‐valine polymorphism at codon 129 of the prion protein gene. Custom‐designed image analysis software was used to produce objective figures for each of the different pathological features throughout 13 different areas of the brain used for analysis. A significant positive correlation was observed between prion protein deposition and astrocytosis in all cases and no significant correlation was observed between spongiform change and prion protein deposition. Different patterns of pathology were found to relate to codon 129 genotype; valine homozygosity favoured the targeting of pathology to deep grey matter structures, while methionine homozygosity favoured cortical targeting of pathology. These results provide evidence that prion protein deposition is closely associated with an astrocytic reaction and suggest that codon 129 genotype may influence the pathological phenotype.
Cyclin D1 in astrocytic tumours: an immunohistochemical study
Authors: Chakrabarty A. , Bridges L. R. , Gray S.
Published: May 2008

Forty‐eight astrocytic tumours were stained immunohistochemically with antibodies to the cell cycle‐regulating protein, cyclin D1, and to the proliferation marker MIB1 (Ki‐67) using formalin fixed paraffin embedded tissue and a microwave antigen retrieval system. Cases were classified by the WHO system (1993). The labelling indices (LI) for both antibodies were compared with each other and with the tumour type. The mean labelling indices for both antibodies increased with the degree of malignancy, and a significant difference was seen between the pilocytic astrocytoma and diffuse astrocytoma together vs anaplastic astrocytoma and glioblastoma together. However, within each tumour type there was considerable variation in the labelling indices and a clear cut off value could not be demonstrated. There was a strong positive correlation between labelling indices for cyclin D1 and MIB1 in diffuse astrocytoma, but this correlation broke down increasingly in anaplastic astrocytoma and glioblastoma. There was poor correlation between cyclin D1 and MIB1 in pilocytic astrocytoma, a feature which appeared to separate them from the diffuse astrocytoma. Average labelling indices for cyclin D1 were higher than those of MIB1, which suggests that cyclin D1 positive cells represent a pool of cells from which proliferation and hence MIB1 expression can take place. In conclusion, cyclin D1 is overexpressed in astrocytic tumours, more so with increasing grade of malignancy and in a way which approximately correlates with MIB1 expression.
Hyperbaric oxygenation prevents delayed neuronal death following transient ischaemia in the gerbil hippocampus
Authors: Kondo A. , Baba S. , Iwaki T. , Harai H. , Koga H. , Kimura T. , Takamatsu J.
Published: May 2008

The mechanism of the neuroprotective effect of hyperbaric oxygenation remains unclear although its clinical benefits have been well recognized for human ischaemic neuronal disease. The preventive effect of hyperbaric oxygenation against delayed neuronal death was investigated in the gerbil following transient forebrain ischaemia. Delayed neuronal death in the gerbil was produced by clips on both the common carotid arteries (10 min). Morphological examination was carried out after several protocols of hyperbaric oxygenation, modified from the protocols for human ischaemic neuronal disease. Neurons in the hippocampal CA1 were well preserved in the gerbils treated with hyperbaric oxygenation, more so than in the gerbils with no hyperbaric oxygenation. Moreover, more neurons were preserved in the CA1 treated with hyperbaric oxygenation within 6 h of the ischaemia, than when the hyperbaric oxygenation was started 24 h after the ischaemia. The induction of heat shock proteins (HSP72 and HSP27) became weaker in the gerbils with hyperbaric oxygenation than in those without hyperbaric oxygenation, as seen immunohistochemically. We also observed an increase in dense bodies, that were shown to be lysosomes and myelinoid structures in the cytoplasm of the neurons ultrastructurally, in the hippocampus with hyperbaric oxygenation. However, no oxygen toxicity to the neurons was detected, up to at least two atmospheres absolute. This experimental system was useful to investigate the preventive mechanism of hyperbaric oxygenation against delayed neuronal death in the gerbil, and to determine the clinical indications and the most effective protocol for hyperbaric oxygenation for ischaemic neuronal damage in the human brain.
Amyloid deposition is associated with c‐Jun expression in Alzheimer's disease and amyloid angiopathy
Authors: Ferrer I. , Seguí J. , Planas A. M.
Published: May 2008

Since the PAD gene (also called promoter of Alzheimer's disease amyloid A4 precursor gene or amyloid β‐protein precursor promoter) has two AP‐1 consensus sequences, and members of the Fos and Jun families are the major components of the transcription factor activator protein‐1 (AP‐1), we have investigated the localization of c‐Fos and c‐Jun immunoreactivity and its relationship to β‐amyloid deposition in the brains of patients with Alzheimer's disease and amyloid angiopathy. c‐Jun, but not c‐Fos, immunoreactivity is observed in the muscular layer of meningeal and cerebral blood vessels with amyloid angiopathy, and in the soma of glial cells and cellular processes of unknown origin surrounding β‐amyloid deposits in the brain. These results show that c‐Jun may participate in the cascade of events leading to increased β‐APP (β‐amyloid precursor protein) production and β‐amyloid deposition in the brains of patients with Alzheimer's disease and amyloid angiopathy.
Morphology of oligodendrocytes during demyelination in optic nerves of mice infected with Semliki Forest virus
Authors: Butt A. M. , Tutton M. G. , Kirvell S. L. , Amor S. , Jenkins H. G.
Published: May 2008

Multiple sclerosis (MS) is a demyelinating disease which affects oligodendrocytes, the myelinating cells of the CNS. Demyelination is known to occur in the optic nerves of Balb/c mice infected with the avirulent A7(74) strain of Semliki Forest virus (SFV), and many of the changes are similar to those of patients with MS. The aim of the present study was to determine how demyelination proceeds in individual oligodendrocytes in SFV infection, to help in understanding the pathology of demyelination and remyelination in MS. The whole‐cell morphology of individual oligodendrocyte units (defined as the oligo‐dendrocyte, its processes and the internodal myelin segments of the axons it ensheaths) was characterized using intracellular dye injection in isolated intact optic nerves. In untreated control mice, oligodendrocytes had a relatively uniform morphology and each cell on average provided 20 or so nearby axons with single myelin sheaths with internodal lengths of ∼ 150 μm. In SFV infected mice, during the peak of demyelination at post inoculation days 14–21, 55% of oligodendrocytes displayed a range of morphological abnormalities, which most likely represented sequential changes in oligodendrocytes during demyelination. Thus, at the earliest stage of demyelination oligodendrocytes developed swellings or vacuolations along their internodal myelin sheaths, which became gradually attenuated and were completely lost in extreme cases. The results show that whole oligodendrocyte units were affected during SFV‐induced demyelination and this is the basis of the focal nature of lesions in this viral model of MS. Individual oligodendrocyte units which had lost their full complement of myelin sheaths had the appearance of immature oligodendrocytes, suggesting they had undergone de‐differentiation. We concluded that these cells may not be destroyed during demyelination and it is possible they are capable of remyelination which is a feature of SFV infection in mice and MS in humans.
Apoptosis and necrosis in the newborn piglet brain following transient cerebral hypoxia–ischaemia
Authors: Yue X. , Mehmet H. , Penrice J. , Cooper C. , Cady E. , Wyatt J. S. , Reynolds E. O. R. , Edwards A. D. , Squier M. V.
Published: May 2008

We have used a porcine model of global hypoxia–ischaemia to examine the mode and extent of cell damage to the newborn brain. Apoptosis and necrosis were observed in neurons and glial cells following transient cerebral hypoxic–ischaemic injury (HII) by haematoxylin and eosin staining and by in situ end labelling (ISEL). Quantitative neuropathological analysis of the cingulate gyrus, the hippocampus and the cerebellum showed that the degree of both apoptosis and necrosis increased with the severity of injury in these brain areas. The hippocampus and cerebellar cortex were particularly sensitive to HII. Furthermore, some cell types were more susceptible to a particular mode of cell death. In the cerebellum, Purkinje cells died by necrosis but never by apoptosis. In contrast, cerebellar granule cells were frequently apoptotic, but never necrotic. In the hippocampus, apoptosis occurred in the inner layer neurons of the dentate fascia and necrosis in the more mature outer layer neurons. This suggests that immature neurons may be more prone to apoptotic death while terminally differentiated neurons die by necrosis. Apoptosis but not necrosis was seen in cerebral white matter. This model may help to elucidate the factors that determine cell fate following HII and aid the development of cerebroprotective strategies.
A comparative freeze‐fracture study of plasma membrane of dystrophic skeletal muscles in dy/dy mice with merosin (laminin 2) deficiency and mdx mice with dystrophin deficiency
Authors: Shibuya S. , Wakayama Y. , Oniki H. , Kojima H. , Saito M. , Etou T. , Nonaka I.
Published: May 2008

The intramembranous particle (IMP), orthogonal array (OA) and orthogonal array subunit particle (OASP) densities of skeletal muscle plasma membranes of merosin deficient dy/dy mice and their control mice at 7, 14 and 28 days after birth were analysed by freeze‐fracture electron microscopy. Similar studies were performed on dystrophin‐deficient mdx mice with mild muscle weakness at 28 days after birth for the comparison with those of dy/dy mice with severe muscle weakness at the same age. In the pre‐clinical stage of dy/dy mice at 14 days after birth, the membranes showed a significantly decreased density of OAs (P<0.01 by Wilcoxon rank‐sum test) as compared with control mice, while those in the clinical stage of dy/dy mice at 28 days after birth showed normal IMP density but a marked depletion of OA density (P<0.01). Moreover, at 28 days after birth, the reduction of OAs in the plasma membranes of dy/dy mice was more marked than that of mdx mice (P<0.05 by Wilcoxon rank‐sum test). These results provided us with the information that the OA density was affected more severely with merosin deficiency than with dystrophin deficiency, and again supported our previously proposed concept that the clinical severity in muscular dystrophies correlated with the OA density.
Viliuisk encephalomyelitis — review of the spectrum of pathological changes
Authors: McLean C. A. , Vladimirtsev V. A. , Prokhorova I. A. , Goldfarb L. G. , Asher D. M. , Vladimirtsev A. I. , Alekseev V. P. , Gajdusek D. C.
Published: May 2008

Viliuisk encephalomyelitis (VE) is an unique neurological disease occurring in the Iakut (Sakha) people of Siberia. Evolution of the disease follows one of three broad clinical forms: subacute, slowly progressive or chronic. Death occurs within 3 to 6 months in subacute cases and within 6 years in the slowly progressive cases. Chronic cases lack a subacute phase but show a slowly progressive dementia associated with bradykinesia, dysarthria and spastic paraparesis that stabilizes late in the disease process. In subacute and slowly progressive cases, focal necrotizing encephalomyelitis is seen at necropsy. Chronic cases show multifocal areas of lysis with a gliotic margin, predominantly within grey matter, lacking associated chronic inflammatory changes seen in the other forms of the disease. Epidemiological studies are consistent with a disease of low‐grade communicability, but laboratory studies have so far failed to reveal an infectious organism. The spectrum of neuropathological changes are reviewed in this examination of 11 cases. Although the aetiology of VE remains obscure, further studies are warranted since it may represent a novel disease process.
The role of the polyamine inhibitor eflornithine in the neuropathogenesis of experimental murine African trypanosomiasis
Authors: Jennings F. W. , Gichuki C. W. , Kennedy P. G. E. , Rodgers J. , Hunter C. A. , Murray M. , Burke J. M.
Published: May 2008

The treatment of late‐stage human African trypanosomiasis is complicated by a post‐treatment reactive encephalopathy, also referred to as a ‘reactive arsenical encephalopathy’, that may be fatal. This study used a well established experimental mouse system to assess the use of the trypanostatic drug, eflornithine, in the management of this post‐treatment reaction. Female CD‐1 mice infected with an eflornithine‐resistant trypanosome stabilate and treated with the trypanocidal compound diminazene aceturate on or after day 21 post‐infection develop a reactive encephalopathy and relapsing parasitaemia. If these animals are re‐treated with diminazene aceturate, a severe encephalopathy develops histologically comparable with that of human cases and characterized by a severe meningoencephalitis and astrogliosis. Histopathological and immunocytochemical examination shows that administration of eflornithine before or after the development of this reactive encephalopathy prevented or ameliorated the inflammatory reaction. Since an eflornithine resistant stabilate was used, this effect appears to be independent of the drug's trypanostatic action and illustrates an important, previously unrecognized, pharmacological property of eflornithine. Consideration can now be given to the use of eflornithine for the management of human trypanosomiasis cases, even where trypanosome resistance to eflornithine exists.
The distribution of amyloid β protein deposition in the corpus striatum of patients with Alzheimer's disease
Authors: Brilliant M. J. , Elble R. J. , Ghobrial M. , Struble R. G.
Published: May 2008

The distribution of amyloid β protein deposition in the corpus striatum of patients with Alzheimer's disease The distribution of amyloid β peptide (Aβ) was quantified in the corpus striatum and pallidum of 10 patients with Alzheimer's disease (AD) and three patients with both Alzheimer's disease and Parkinson's disease (AD–PD). Aβ occurred almost exclusively in plaques that did not have neurites or amyloid cores. Caudate, accumbens nuclei and rostral putamen contained more of the diffuse plaques than did caudal putamen. No diffuse plaques were found in the neighbouring globus pallidus. This distribution of Aβ deposition may reflect the distribution of diseased synaptic cortical afferents rather than a putative vascular source of Aβ.
Case report
Authors: Love S. , Bateman D. E. , Hirschowitz L.
Published: May 2008

S. Love, D. E. Bateman and L. Hirschowitz (1997) Neuropathology and Applied Neurobiology, 23, 512–515

Case report. Bilateral λ light chain amyloidomas of the trigeminal ganglia, nerves and roots

We describe a patient who developed chronic bilateral trigeminal neuropathy that was found at autopsy to be due to λ light chain amyloidosis involving the trigeminal nerves, ganglia and roots bilaterally, as well as part of the intrapontine course of the trigeminal nerve fibres. No amyloid was found elsewhere in the nervous system or systemically. Review of previous reports indicates that the clinical features of trigeminal amyloidosis are quite stereotyped, with initial trigeminal neuralgia or dysaesthesiae, and subsequent development of facial anaesthesia and weakness of muscles of mastication. The disorder is usually unilateral but may rarely, as in the present case, occur bilaterally.
Protein microarray analysis identifies human cellular prion protein interactors
Authors: Satoh J. , Obayashi S. , Misawa T. , Sumiyoshi K. , Oosumi K. , Tabunoki H.
Published: May 2008

Aims: To obtain an insight into the function of cellular prion protein (PrPC), we studied PrPC‐interacting proteins (PrPIPs) by analysing a protein microarray. Methods: We identified 47 novel PrPIPs by probing an array of 5000 human proteins with recombinant human PrPC spanning amino acid residues 23–231 named PR209. Results: The great majority of 47 PrPIPs were annotated as proteins involved in the recognition of nucleic acids. Coimmunoprecipitation and cell imaging in a transient expression system validated the interaction of PR209 with neuronal PrPIPs, such as FAM64A, HOXA1, PLK3 and MPG. However, the interaction did not generate proteinase K‐resistant proteins. KeyMolnet, a bioinformatics tool for analysing molecular interaction on the curated knowledge database, revealed that the complex molecular network of PrPC and PrPIPs has a significant relationship with AKT, JNK and MAPK signalling pathways. Conclusions: Protein microarray is a useful tool for systematic screening and comprehensive profiling of the human PrPC interactome. Because the network of PrPC and interactors involves signalling pathways essential for regulation of cell survival, differentiation, proliferation and apoptosis, these observations suggest a logical hypothesis that dysregulation of the PrPC interactome might induce extensive neurodegeneration in prion diseases.
Improved strategy for screening prospective blood donors for anaemia
Authors: Boulton F. E. , Nightingale M. J. , Reynolds W.
Published: May 2008

SUMMARY. Women (568) and men (531) attending blood donation sessions in Wessex in September, 1992, were assessed for anaemia by the standard CuSO4 method on finger‐prick (FP) blood samples. The haemoglobin (Hb) concentration on FP samples and on venous blood was also checked using the HemoCue. Different FP samples from the same donors revealed a wide variation on HemoCue. We recommend retaining the CuSO4 method on FP samples as the initial screen, and follow‐up of apparent failures by determining the Hb concentration on venous sampling with the HemoCue. As 54% of females were found on venous samples to be below the current recommended threshold (125 g/L) for Hb concentration, we also recommend lowering the threshold to 115 g/L for women, and to 130 g/L for men. We further recommend a close re‐examination of normal haematology values for adults.
Mulched cover crops as an alternative to conventional weed management systems in vineyards
Authors: STEINMAUS S , ELMORE C L , SMITH R J , DONALDSON D , WEBER E A , RONCORONI J A , MILLER P R M
Published: May 2008

Conventional methods of weed management in vineyards rely primarily on herbicides and tillage. The desire to adopt alternatives to these methods is driven by environmental and economic reasons. Weed suppression and grape yield under mulched cover crop systems at two rainfed northern California vineyards were similar to, and at times exceeded, those under conventional tillage or herbicide management. Cover crop productivity was positively correlated with weed suppression and mulch decomposition rates and seemed to be determined primarily by location and then by cover crop type. The mulch from mowed cover crops averaged 603(± 94) gm−2 at the two sites. Weed suppression was linked to light interception by the mulch cover for most weed species. Subterranean clover planted directly in the vine row significantly reduced weed cover where it established. The increased dominance of the perennial Convolvulus arvensis and reduction of certain annual species was indicative of species compositional changes in all treatments. Profits under the cover cropping systems exceeded those under conventional tillage and herbicide systems by € 794 ha−1 averaged over the duration of the experiment at both locations.
Investigation of threatened arable weeds and their conservation status in Turkey
Authors: TÜRE C , BÖCÜK H
Published: May 2008

Agronomic operations carried out in arable lands may cause changes in weed populations and also decrease the number of animal species that depend on these weed species. An emerging paradigm is the conservation and sustainability of weed species. In this study, risk status of arable weeds in Turkey was evaluated and it was determined that 112 of them (76 endemic and 36 non‐endemic species) were at risk according to the IUCN Red List. Turkey is extremely diverse, with over 3000 endemic plant species out of nearly 12 000 recorded. Considering endemic weeds, they are classified in the following risk categories: critically endangered (four weed species), endangered (EN) (six), vulnerable (VU) (14), near threatened (seven), least concern (41) and data deficient (DD) (four species). Among the non‐endemic weeds, three species are EN, 31 VU and two are DD. The families with the highest threatened weed species are Scrophulariaceae, Fabaceae, Asteraceae, Brassicaceae and Lamiaceae. The identification of weed species in arable habitats and their risk status is a useful tool for assessing and monitoring how the sustainability of weed populations is affected by farming practices. The results show the necessity of adopting new environment‐friendly agricultural methods to conserve the high number of endemic weed species under threat in Turkey.
Bone mineral density and bone turnover markers in patients receiving a single course of isotretinoin for nodulocystic acne
Authors: Tekin Nilgun Solak , Ozdolap Senay , Sarikaya Selda , Keskin Selda Isık
Published: May 2008

Background High‐dose isotretinoin has been reported to have adverse effects on bone mineral density (BMD); however, studies evaluating changes in BMD with isotretinoin therapy at different dosages and with varying treatment durations have produced conflicting results.

Objective To investigate the effect of a standard, single course of isotretinoin therapy on BMD and bone turnover markers in patients with nodulocystic acne.

Methods Thirty‐six patients (15 male, 21 female) with severe, recalcitrant, nodulocystic acne and 36 healthy controls (16 male, 20 female) were enrolled in the study. Patients received isotretinoin treatment for 4–6 months until a cumulative dose of 120 mg/kg had been achieved. BMD in the lumbar spine and femur was measured at baseline and at the end of therapy by dual‐energy X‐ray absorptiometry. Serum calcium, phosphate, parathormone, total alkaline phosphatase, osteocalcin, free deoxypyridinoline, and urinary calcium were also measured before and at the end of treatment.

Results No significant differences were found in lumbar spine and femoral BMD between the patient and control groups at the beginning of the study (P > 0.05), and no statistically significant difference was observed between the BMD values in patients at the beginning vs. the end of treatment (P > 0.05). No statistically significant difference in bone turnover markers was found between patients and controls at the beginning of the study (P > 0.05), and no statistically significant changes in bone turnover markers were observed in patients at the beginning vs. the end of treatment (P > 0.05).

Conclusion A single course of isotretinoin therapy has no clinically significant effect on bone metabolism.
Clinicopathologic challenge: Linear brown macules on the chest and arm
Authors: Erkek Emel , Bozdogan Onder , Sanli Cihat , Ozoguz Pinar
Published: May 2008

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Hematopoietic stem cell transplantation in a CD3γ‐deficient infant with inflammatory bowel disease
Authors: Turul Özgür Tuba , Türkkanı Asal Gülten , Çetinkaya D. , Orhan D. , Kılıç S. Ş. , Usta Y. , Özen H. , Tezcan İlhan
Published: May 2008

Abstract:  Partial or total CD3 chain expression defects including CD3 gamma, epsilon, delta, and zeta chain are among the autosomally inherited SCID presenting with T−B+NK+ phenotype with lymphopenia. The clinical findings are generally severe in all except for CD3 gamma deficiency. Here we present a 10‐month‐old CD3 gamma deficient boy with IBD. The patient had suffered from intractable diarrhea, recurrent pulmonary infections and oral moniliasis since two months of age. Following the first allogeneic HSCT from his HLA‐identical (6/6) sister after a reduced intensity regimen, a second transplantation was performed five months later. On day +19 after second transplantation, the CD3 TCR alfa/beta chain expression increased to 66% with development of full donor chimerism (98.6%). A significant improvement in diarrhea, perianal lesions, and rectal fistula was observed suggesting an improvement in inflammatory bowel disease. The patient died at home on day +50 with a sudden respiratory failure secondary to an undetermined infection. The case was interesting being the first reported case with SCID and inflammatory bowel disease who responded very well to HSCT by full recovery of intractable diarrhea, failure to thrive, laboratory findings, and improvement of fistula formation.
Unusual case of Epstein–Barr virus DNA tissue positive: Blood negative in a patient with post‐transplant lymphoproliferative disorder
Authors: Levenson Brian M. , Ali Sabina A. , Timmons Charles F. , Mittal Naveen , Muthukumar Alagar , Payne Deborah A.
Published: May 2008

Abstract:  Detection of PTLD uses PCR to detect circulating EBV DNA in the blood or in situ hybridization to identify EBV DNA in tissue biopsies. EBV DNA was detected in the tissue section using both real‐time PCR and in situ hybridization. We report an unusual presentation of PTLD with no detectable EBV DNA in the blood using EBER‐1 and EBNA‐1 PCR assays. This report suggests that the use of EBV‐PCR for the early detection of PTLD in blood samples may not be 100% effective in detecting disease.
Mycotic pseudoaneurysm following a kidney transplant: A case report and review of the literature
Authors: Osmán Ignacio , Barrero Rafael , León Eduardo , Medina Rafael , Torrubia Francisco
Published: May 2008

Abstract:  Vascular complications represent a significant cause of morbidity and mortality following a kidney transplant. Pseudoaneurysms are rare, occurring in approximately 1% of cases. We present a 15‐yr‐old patient who received a kidney transplant in the right iliac fossa. Thirty‐six days following the transplant, the patient was admitted to the hospital because of a marked increase in serum creatinine levels, arterial hypertension, scrotal edema, and lower right limb pain. The patient did not present fever or raised inflammatory markers. A pseudoaneurysm was diagnosed by means of a Doppler echography and a CT. By a selective arteriography of the right iliac artery, we placed a 8 × 5 cm stent to isolate the pseudoaneurysm, due to the high risk of an extensive defect occurring in the arterial wall. Forty‐eight h later the patient underwent transplant nephrectomy. Seven days following surgery, the patient experienced febrile syndrome and therefore another CT was carried out which showed a large abscess around the stent. So we decided to perform another intervention in order to drain this abscess. Due to the extensive loss of the arterial wall where the prosthesis was largely exposed, we ligated the common iliac and external iliac arteries, removed the prosthesis and performed a femoro‐femoral bypass with the usual subcutaneous positioning of the prosthesis (separate from surgical site). The stent and mural thrombus were sent for culture analysis and Candida albicans was observed. The diagnosis of a pseudoaneurysm in these types of patients continues to be considered as a surgical emergency by the majority of authors. Transplantectomy is the most frequently used treatment technique. Positioning a stent prior to transplantectomy avoids ligature of the iliac artery in the majority of cases.
Arterial Vascularization of the Uropygial Glands (Gl. Uropygialis) in the Japanese Quail (Coturnix coturnix japonica) and Silver Polish (Gallus gallus domesticus)
Authors: Atalgin H. , Kürtül İ.
Published: May 2008

This study focused on the morphological characteristics of the uropygial glands of the Japanese quail and silver polish, particularly the arterial nourishment. With this respect, coloured‐latex injected animals were dissected and their glands and related arteries were observed. The gland in the Japanese quail was relatively longer than that in the silver polish. The first caudal segmental arteries in the Japanese quail were specialized as the uropygial gland artery while the fourth caudal segmental ones were continued as the uropygial gland artery in the silver polish. Branches from the second and third caudal segmental arteries and skin also contributed bilaterally to the vascularization of the gland in the Japanese quail. Observing the more complex arterial structure in the Japanese quail suggests more active uropygial gland in this species, when compared with the silver polish.
Morphological Investigations on the Circulus Arteriosus Cerebri in Mole‐Rats (Spalax leucodon)
Authors: Aydin A. , Yilmaz S. , ÖZkan Z. E. , Ilgün R.
Published: May 2008

The aim of the present study is to investigate the circulus arteriosus cerebri in mole‐rats (Spalax leucodon). Six adult mole‐rats were used for this purpose. Coloured latex was injected into the left ventriculus of the hearts of all the animals. After careful dissection, the circulus arteriosus cerebri (the circle of Willis) was investigated. The cerebrum and the cerebellum were supplied by the internal carotid‐ and the basilar arteries respectively forming the circulus arteriosus cerebri in mole‐rats. In the investigated objects, the internal carotid‐ and the basilar arteries were not united directly and for this reason the circulus arteriosus cerebri was not formed completely in mole‐rat. The branches supplying the medulla oblongata and the cerebellum originate from the basilar artery formed by union of the left and right vertebral arteries and the internal ophthalmic, the caudal cerebral, the choroid, the median cerebral, the rostral cerebral arteries originated from the internal carotid artery. After giving off the medial cerebral artery, the right and left rostral cerebral arteries on every two sides divided into the lateral and medial twin branches and by union of the lateral branches the internal ethmoidal artery, and by union of the medial branches, the ramus extending to facies medialis cerebri were formed. The ramus extending to the facies medialis cerebri was anastomosed with the branch of the caudal cerebral artery on the back of the corpus callosum. The last part of the basilar artery gave the two branches running toward the right and left side on the pontocrural groove (sulcus pontocruralis) and every one of these branches ramified into two rami. One of these rami formed into the rostral cerebellar artery and the other one extended to the tectum mesencephali. In conclusion, the arterial circle of the cerebrum and cerebellum was supplied by the internal carotid artery and the basilar artery respectively in mole‐rats.
Developments in the epidemiolgy of invasive fungal infections – implications for the empiric and targeted antifungal therapy
Authors: Hof H.
Published: May 2008

Invasive fungal infections are significant causes of morbidity and mortality in hospitalized, immunocompromised patients. Whereas in hematologic patients aspergilli represent the major problem along with Candida spp., in surgery departments yeast infections are more prevalent. For the empiric as well as the targeted therapy of mould infections with high mortality rates, several antifungals can be given alone or in combination. So far, resistance among aspergilli is uncommon. In yeast infections one has to respect that a relatively large number of causative agents, especially Candida glabrata and C. krusei, can be resistant to azoles, in particular to fluconazole; cross‐resistance with other triazoles, such as voriconazole, may occur as well. Coverage of most pathogens involved in life‐threatening fungal infections is crucial for empiric treatment. Since caspofungin has a broad spectrum of antifungal activities and is effective even against fungi with azole resistance, this drug should be preferred for initial, empiric therapy of yeast infections, since there are practically no caspofungin resistant strains among clinical isolates. Early start with an adequate empirical antifungal therapy is associated with an improved survival of patients with invasive Candida infections. Once the diagnosis is completed and a susceptibility pattern of the causative agent is available, a targeted therapy can be given respecting pharmacology, side effects and interactions with co‐administered drugs.